UA109553C2 - Substituted imidazopiridazines - Google Patents

Abstract

The present invention relates to substituted imidazopyridazines of the general Formula I, (I) wherein R, R and A are as defined in the claims, methods of preparing said compounds, pharmaceutical compositions and combinations containing said compounds, and the use of said compounds for the preparation of a pharmaceutical composition for treatment or prevention of the disease, in particular hyperproliferative disorder and / or angiogenesis disorder, as a single agent or in combination with other active ingredients.

Description

disease, in particular hyperproliferative disorder and/or angiogenesis disorder, as a single agent or in combination with other active ingredients. I

The present invention relates to substituted imidazopyridazines of the general formula I as described and defined in this document, methods of obtaining the indicated compounds, pharmaceutical compositions and combinations containing the indicated compounds, the use of the indicated compounds to obtain a pharmaceutical composition for the treatment or prevention of a disease, as well as intermediate compounds suitable for to obtain the specified compounds.

Prerequisites of the invention

The present invention relates to chemical compounds that inhibit Mr5-1 (Moporoiag Zripaie 1) kinase (also known as Tyrosine Threonine Kinase, TTK). Mr5-1 is a Zzeg/TPPg dual-specificity kinase that plays a key role in the activation of the mitotic checkpoint (also known as the spindle checkpoint, spindle assembly checkpoint), thus ensuring correct segregation of chromosomes during mitosis (Abgiec A ei ai. , Seiyi, 2001, 106, 83-93.

In each dividing cell, it is necessary to ensure an equal distribution of replicated chromosomes into two daughter cells. At the beginning of mitosis, chromosomes are attached at their kinetochores to the microtubules of the division spindle. The mitotic checkpoint is a control mechanism that is active as long as unattached kinetochores are present and prevents mitotic cells from entering anaphase, and thus from completing cell division with unattached chromosomes.

C), Viospetisa eyi Viorpusisa Asia, 2008, 1786, 24-31; Myzasspio A apa ZaItop EO, Mai Nem Moi

Sow! Vio!I., 2007, 8, 379-93|. When all kinetochores are attached in the correct amphitelic, i.e. bipolar, manner to the mitotic spindle, the checkpoint is satisfied and the cell enters anaphase and undergoes mitosis. The mitotic checkpoint consists of a complex network of essential proteins, including members of the MAO (incomplete mitotic block, MAO 1-3) and Bib (benzimidazole-inhibited budding, Bib 1-3) families, the mobile protein CEMP-E, Mpe-1 kinase, and other components, many of which are overexpressed in proliferating cells (for example, cancer cells) and tissues (Uchap Vei ai., SiipisaYi Sapseg Kezeagsi, 2006, 12, 405-101. The essential role of Mp5-1 kinase activity in mitosis checkpoint signaling was shown using RNA hairpin silencing, chemical genetics, as well as chemical inhibitors of the Mr5-1 kinase YuePyita M ega!., R o5 OME, 2008, 3, e2415; dope5 MN ei ai., Sitepi Vioiodu, 2005, 15, 160 -65; bogeg VK her ai.,

Sitepi Vioiodu, 2005, 15, 1070-76; Zsptiadii Mei aI., EMVO Verohiv, 2005, 6, 866-721.

There are many data linking the reduced but incomplete function of the mitotic checkpoint with aneuploidy and oncogenesis (Mueameg VA apa SiIemeiapa OMU, Sapseg Kezeagsp, 2007, 67, 10103-5; Kipd AMU, Viospitis eyi Viorpusisa Asia, 2008, 1786, 4-14|. On the contrary, it turned out that complete inhibition of the mitosis checkpoint leads to significant missegregation of chromosomes and causes apoptosis in cancer cells I(Kor5 03 ei aiYi., Maishge Kemiem5 Sapseg, 2005, 5, 773-85;

Septidius! M apa Medeta VN, Seyi Susie, 2006, 5, 159-635; Zsptiyi M apa Vaviiap5 N, Ogyd

Veviviapse Shoradaiez, 2007, 10, 1162-81) Therefore, abrogation of the mitotic checkpoint by pharmacological inhibition of Mrz5-1 kinase or other components of the mitotic checkpoint provides a new approach in the treatment of proliferative disorders, including solid tumors such as carcinomas and sarcomas, and leukemia, and lymphocytic leukemia or other disorders associated with uncontrolled cell proliferation.

Approved anti-mitotic drugs such as periwinkle alkaloids, taxanes or epothilones activate ALS, causing mitotic arrest by stabilizing or destabilizing microtubule dynamics. This arrest prevents sister chromatids from separating to form two daughter cells. Prolonged mitotic arrest causes the cell to exit mitosis or leads to mitotic catastrophe and cell death.

In contrast, Mp5-1 inhibitors cause inactivation of ZAS, which accelerates the passage of cells through mitosis, resulting in a significant mis. chromosome segregation and cell death.

These data indicate that MP5-1 inhibitors have therapeutic value for the treatment of proliferative disorders associated with accelerated uncontrolled proliferative processes in cells, such as, for example, cancer, inflammation, arthritis, viral diseases, neurodegenerative diseases such as Alzheimer's, cardiovascular disease, or fungal disease in warm-blooded animals such as humans.

Therefore, Mp5-1 inhibitors represent valuable compounds that will complement therapeutic agents, both in a separate form and in combination with other drugs.

In the prior art, various compounds having inhibitory activity against

Mrzv-1 kinase. UUO2010/124826A1 describes substituted imidazoquinazolines as inhibitors of Mr5-1 kinase or TTK. M/O02011/026579A1 describes substituted aminoquinazolines as Mr5-1 inhibitors.

UMO2011/063908A1, UMO2011/064328A1, and UUO2011/063907 Ai describe triazolopyridine derivatives as inhibitors of Mr5-1 kinase.

The use of imidazopyridazine derivatives for the treatment or prevention (610) of various diseases is described:

MO 2007/038314 And? (VgisisIi-Mueg5 Zdciibb Sotrapu) refers to condensed heterocyclic compounds suitable as kinase modulators, including MK2 modulation.

In particular, UMO 2007/038314 A2 concerns imidazo|1,2-b|pyridazines.

US Patent Application SH52008/0045536 A1 (VgivioI-Mueg5 zdciB Sotrapu) also relates to condensed heterocyclic compounds useful as kinase modulators, including MK2 modulation. In particular, it concerns imidazo|1,2-b|pyridazines.

MO 2010/042699 AT (VgisisIi-Mueg5 Zdtsiibb Sotrapu) relates to condensed heterocyclic compounds suitable as kinase modulators, in particular SK2 modulation. In particular,

UMO 2010/042699 A1 concerns imidazo|1,2-b|Ipyridazines substituted with a nitrile in position 3.

MO 2007/025090 A2 (Kaiurzi5, Ips.) relates to heterocyclic compounds suitable as MEK kinase inhibitors. In particular, MO 2007/025090 A? refers to ipieg -aia imidazo|1,2-b|Ipyridazines.

UMO 1998/08847 A1 (Rij?eg, Ips.) relates to heterocyclic compounds suitable as antagonists of the corticotropin-releasing factor (hormone) SKE (SKN). In particular, ULO 1998/08847 A1 refers to the imidazo|1,2-b|pyridazines.

MO 2011/013729A1 describes condensed imidazole derivatives as Mr5-1 inhibitors. Among the described condensed derivatives of imidazole there are also imidazo|/1,2-b|Ipyridazines. For example, UMO 2011/013729A1 describes compounds of formula C1: 7 em

You are 8

MNA

She (in,

С where (Х, У, М, УМ) means (-М-, -С8/-, -М-, -СВ7-), (-СВНе-, -М-, -М-, -СВ8-), ( -М-, -С18-, -М-, -М-) or (-М-, -СВ8'-, -О-, -М-.);

IN? means substituted or unsubstituted cycloalkyl; 27 means the group represented by the formula -МАЗВ" or the group represented by the formula -ОНВ";

A means a substituted or unsubstituted aromatic hydrocarbon ring, a substituted or unsubstituted aromatic heterocyclic ring, a substituted or unsubstituted non-aromatic hydrocarbon ring, or a substituted or unsubstituted non-aromatic heterocyclic ring;

B', VAZ, VU, B" and KU mean a large number of substitutes (see UMO 2011/013729А1, for example, item 1).

The inventors of this invention unexpectedly discovered that compounds of the general formula | as described and defined herein exhibit high Mp5-1 inhibitory activity and show high metabolic stability.

The above-described prior art does not describe the imidazopyridazines of claims 1-8, or a stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof, as described and defined herein, and herein sometimes referred to as " compounds of this invention", or their pharmacological activity and stability. It has now been found that the basis of this invention is the fact that the specified compounds of this invention have unexpected and superior properties.

In particular, it was unexpectedly found that the specified compounds of this invention effectively inhibit

Mrz5-1 kinase and therefore can be used to treat or prevent diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, or inappropriate cellular inflammatory responses or diseases mediated by uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, or inappropriate cellular inflammatory responses, particularly where uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, or inappropriate cellular inflammatory responses are mediated

Mrzv-1 kinase, such as, for example, hematological tumors, solid tumors, and/or their metastases, for example, leukemia and myelodysplastic syndrome, malignant lymphomas, head and neck tumors, including brain tumors and brain metastases, chest tumors, including non - small cell and small cell lung cancer, gastrointestinal tumors, endocrine tumors,

breast tumors and other gynecological tumors, urological tumors, including kidney, bladder and prostate tumors, skin tumors, and sarcomas, and/or their metastases.

Summary of the invention

This invention includes compounds of the general formula I: in? not 2 Mn

Fe xx M

AND

Eat where:

A means elm, willow, willow

N

4r i A zh M zh IF) y y y y vya 7 vie vie

Vie in'? NM in? in'? NM in? or or d'z I -x vie dm 4r

And HE

- ve or -group; where " indicates the place of attachment of the specified groups to the molecule; 2 means -С(-О)М(Н)А: or -С(-5)М(Н) В, or a group selected from I рп-8Е- "y -E M- rUlch Al

Hn Hn MN M and M Ya

MI MI-- MI-- 2 2 2 2 2 M M

В В А Н х Н дж ; V Y ; t MN

Y I sha MN pl

Cats S

M 2 2 x ! - M 2

НВВВ -М ж А where " indicates the place of attachment of the indicated groups to the molecule:

IN? means a hydrogen atom, or C.i-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bev)M-C-Cv-alkyl, HO-C1-Cv-alkyl, -C1-Cv-alkyl-"CM .

where the indicated C3-Cv-cycloalkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 groups selected from the following: halogen, -OH, -CM, C1-Cv-alkyl, Ci-Cv- alkoxy-, halo-C1-

St-alkyl-;

BZ means a hydrogen atom or a halogen atom, or -CM, C1-Cv-alkyl, Ci-Cv-alkyl-, -(CHg)t-Seg-

C-alkenyl, /-(CHg)t-C4-Cv-cycloalkenyl, /-(CHg)t-Cg2-Cv-alkynyl, /-«(CHg)t-C3-Ce-cycloalkyl, -(CHe)t- (3-7-membered heterocycloalkyl), -(CNeg)t-(4-8-membered heterocycloalkenyl), aryl-C1-Cv-alkyl, heteroaryl-C:-Cv-alkyl, halo-C1-Cv -alkyl, Kba(Bei)M-C1-Cv-alkyl, halo-C1-Cv- alkoxy-C1-Cv- alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cv-alkenyl-, Ca -Св-cycloalkenyl-, С2-

C1-C8-alkynyl-, aryl-, -C1-C8-alkyl-aryl, -C1-C8-alkyl-heteroaryl, heteroaryl-, C1-C8-alkyl-xX-, 10. -X-(CNeo)t-C2- Св-alkenyl, -Х-(СНег)т-Са-Св-cycloalkenyl,. -X-(CHg)t-C2-Cv-alkynyl, -X-(CHg)t-C3-Cv-cycloalkyl, -X-(CHg)t-(3-7-membered heterocycloalkyl), -X- (CHg)t-(4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-Xx-, -C(-0)H8E, -C(-O)M(H)NYA, /-C(-O )М(Веа)Ве», -(-03)0-Не, -М(Вба)Ве», -МО», -Ш(Н)С(-О0)Не, -Оов8е, -5185, -5( -0O)He, -5(-0)2H85, -5(-0(-M Aa), -5(-0)2M(HeB) Ves, -5-(CHg)p-M(Hba) Be» or -5-(CHn)n-(3-7-membered heterocycloalkyl); where C:-Cn-alkyl, Cn-Cn-alkoxy-, -(CHn)t-C2-Cn-alkenyl, -(CHn) is indicated t-C2-Cv-alkynyl, -(CH2g)t-C3-Cv-cycloalkyl, aryl-Ci-Cv-alkyl, heteroaryl-C1-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, Cg -C8-alkenyl-, C1-C8-cycloalkenyl-, C8-C8-alkynyl-, aryl-, C1-C8-alkyl-X-, /-X-(CHg)t-C2-C8-alkenyl, /- X-(CHn)t-Ca-Cv-cycloalkenyl, /-X-(CHng)t-C2-Cv-alkynyl, -X-(CHn)t-C3-Cv-cycloalkyl, -X-(CHn)t- (3-7-membered heterocycloalkyl), -X-(CHg)t-(4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-x-, -C1-Cv-alkyl-aryl, -C1i-Cv- alkyl-heteroaryl or heteroaryl- is optionally substituted, identical or p about different, 1, 2, 3, 4 or 5 KE" groups; да, ДЬ, дъе, ДЯ mean, independently of each other, hydrogen or a halogen atom, or -СМ,

Ci-Cv-alkyl, Ci-Cv-Alkoxy-, halo-Ci-Cv-Alkyl, Kba(Nev)M-C1-Cv-Alkyl, HO-C1-Cv-Alkyl, Ci-Cv-Alkoxy-C1-Cv -alkyl, halo-C1-Cv-Alkoxy-C1-Cv-alkyl, -C(-O)H8E, -C(-O)M(H)Aea, -C(-O)M(Nea)Be", -6b(-0)0-He, -M(Veg)Ve -MO», -M(H)C(-0)8E, -M(Be)c(-0)85, -Щ(Н)С (-OM(Ve Ve", -M(Veg)c(-O)M(Ve)Ve", -M(H)C(-0O)ONE, -M(Ve)C(-0)08E, - М(Н)Б(-О)ВЕ, "(Ве 8(-О)8е, -М(Н)Б(-0)28Я, -М(Neg)5(-0)286, -М-5( -0О)(Нба)ВАей -ОНЯ, -О(С0-0)Н85, -О(С-О)М(Нег) Бе», -б(0-Ф0)0НЕ, -5Бе, -5(-0 )86, -5(-0)M(H)VE, -5(-O)M(Vg)VE, -5(-0)286, -5(-0)2M(H)Ve", -( -0)2m(Veg)Ve", -5(-0)(-M Ag) Ve;

IN? means a hydrogen atom, or Ci-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CnHg )t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bei)M-C1-Cv-alkyl, HO- S.:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cv-alkenyl-, C4-Cv- cycloalkenyl-, C1-C8-alkynyl-, aryl- or heteroaryl-; where Ci-Cv-alkyl, -(CHg)n-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-membered heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-C1-Cv-alkyl, halo-Ci-Cv-alkyl, Kba(Neu)M-C1-Cv-alkyl,, HO-C1- C1-alkyl, -C1-Cv-alkyl-СМ, C1-Cv-Alkoxy-C1-Cv-alkyl, halo-C1-Cv-alukoxy-C1-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-- linoleic heterocycloalkyl, C4-Cv- cycloalkenyl-, aryl- or heteroaryl- is optionally substituted, identically or differently, by 1, 2, C or 4 P8 groups;

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C--

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kea(Nev)M-C1-Cv-alkyl, HO- C:1-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-ОО)НЕ, -с(-ОМ(Н)Веа, -С(-ОМ(Вег) Veh, -b(-0)0-8e, -M(Veg)Ve», -MO», -Ш(Н)С(-О)Вe, -M(Veg)С(-О)8e, -M (Н)С(-О)М(Вег)Ве», -М(Вес)С(-О)М(Веа)Ве, -Ж(Н)С(-О)ОВе, -М(Ве)с( -0)О8е, -ШХН)В(-ОВе, -М(Вег)5(-0)8Е, -М(Н)Я(-0)28Е, -М(Бе5(-0)286, -М- 5(-О)(Be)Be, -ОБе, 0 -О(С-О)8е, -О(0-О)М(Неа)Бе -О(0-0)ОНЯ, -585, -5( -0)Н8, -5(-0)М(Н)АЯ, -5(-0О)М(НЯ)Бе», -5(-0)2Н, -(-0)2М(Н)Бе, - 5(-0)2M(Be2)Be? or -5(-0-MVeg)Be; where the indicated C-C-Alkoxy-, aryl- or heteroaryl- is optionally substituted, identically or differently, 1, 2 or With Ci-Cv-alkyl-, Ci-Cv-Alkoxy-, halo-C1-Cv-Alkoxy-, -C(-0)0O-HE or -OH; or when 2 KK" groups are in the ortho position to each other one on an aryl or heteroaryl ring, the specified 2 K" groups together form a bridge: "О(Снгаг5о "О(СнНаУО), "МН(С(-ОУМН), where " means the place of attachment of the specified aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl,

Vba(de)M-Si-Cv-alkyl, HO-C:-Cv-alkyl, Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, Co-Cv -alkenyl-, C-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-0)НЕ, -ФШ(-ОМ(Н)АЯа, -С(-О)М(Вта)Бей, -С (-0)0-86, -M(Вба)Ве», -MO», -М(Н)С(-О)Н8е, -М(Нег)С(-О)8е, -МН)С(- О)М(На)Ве, «(Не С(-О)М(Ата)Ве, -М(Н)С(-О)ОВе, -М(Не)С(-ООНВе, -МЩ(Н))( -ОНе, -М(Нбг)5(-0)Н8Я, -М(Н)Б(-О0)28?, -М(Нбг)5(-0)2НА, -М-5(-О)(Н) )BA -ОВ8б, 0 -О(0-О)В8е, -О(С-О)М(Неа)ВЯ» -О(0-0)0ОН?, -586, -5(-0)Н88, - 5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, -(-0)2МЩ(Н)Не, -55-0)2М(а )Ve, -5(-0)(-M Ag) or -5(-0)2-(3-7-membered heterocycloalkyl); where the specified 3-7-membered heterocycloalkyl- or heteroaryl- is optionally substituted , identically or differently, 1, 2, C or 4 C-Cv-alkyl-; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5;

X stands for 5(О)р, О, MA, СВЯаде» or САС rad; p means an integer 0, 1 or 2; or a stereoisomer, a tautomer, an M-oxide, a hydrate, a solvate, or a salt thereof, or a mixture thereof.

The present invention also relates to methods of obtaining the indicated compounds, pharmaceutical compositions and combinations containing the indicated compounds, the use of the indicated compounds for obtaining a pharmaceutical composition for the treatment or prevention of disease, as well as intermediate compounds suitable for obtaining the indicated compounds.

Detailed description of the invention

The terms used in this description preferably have the following meanings:

The term "halogen atom" or "halo-" means a fluorine, chlorine, bromine or iodine atom, preferably a fluorine, chlorine, bromine or iodine atom.

The term "Ci-Cv-alkyl" preferably means a linear or branched, saturated, monovalent hydrocarbon group containing 1, 2, 3, 4, 5 or 6 carbon atoms, for example methyl, ethyl, propyl, butyl, pentyl, hexyl, iso-propyl, iso-butyl, sec-butyl, tert-butyl, iso-pentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neo-pentyl, 1,1-dimethylpropyl, 4 -methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl,

3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl, or 1,2-dimethylbutyl, or its isomer. In particular, the specified group has 1, 2, 3 or 4 carbon atoms ("C1-C4-alkyl"), for example, methyl, ethyl, propyl, butyl, iso-propyl, iso-butyl, sec-butyl, tert-butyl , more specifically, 1, 2 or 3 carbon atoms ("C1-C3-alkyl"), for example methyl, ethyl, n-propyl- or iso-propyl.

The term "halo-C1-Cv-alkyl" preferably means a linear or branched, saturated, monovalent hydrocarbon group, wherein the term "Ci-Cv-alkyl" is as defined above, and one or more hydrogen atoms are replaced by a halogen atom, identically or similarly different, that is, one halogen atom is independent of another. In particular, the specified halogen atom means P. The specified halo-C1-Cv-alkyl means, for example, -СЕ3, -СНЕ», -СНоЕ, -СР2СЕ:з, or -СНоСЕ:».

The term "Ci-Cv-Alkoxy" preferably means a linear or branched, saturated, monovalent, hydrocarbon group of the formula -O-C1-Cv-Alkyl, where the term "Ci-Cv-Alkyl" is as defined above, for example, methoxy, ethoxy, n -propoxy, iso-propoxy, n-butoxy, iso-butoxy, tert-butoxy, sec-butoxy, pentoxy, iso-pentoxy, or n-hexoxy, or an isomer thereof.

The term "halo-C 1 -C 6 -alkyl" preferably means a linear or branched, saturated, monovalent C 1 -C 6 -alkyloxy, as defined above, wherein one or more hydrogen atoms are substituted, identically or differently, by one or more atoms halogen In particular, the indicated halogen atom means P. The indicated halo-Ci-Cv-alkoxy means, for example, -ОСЕ», -ОСНЕ», -ЮОСНОЕ, -OSH2СЕ:», or -ОСНоСЕ:.

The term "C1-C1-Alkoxy-C1-C1-Alkyl" preferably means a linear or branched, saturated, monovalent C1-C1-C8-alkyl as defined above, wherein one or more hydrogen atoms are substituted, identically or differently, by C -S-C-Alkoxy group as defined above, for example, methoxyalkyl, ethoxyalkyl, propyloxyalkyl, iso-propoxyalkyl, butoxyalkyl, iso-butoxyalkyl, tert-butoxyalkyl, sec-butoxyalkyl, pentyloxyalkyl, iso-pentyloxyalkyl, hexyloxyalkyl, or an isomer thereof.

The term "halo-C1-C1-Alkoxy-C1-C1-Alkyl" preferably means a linear or branched, saturated, monovalent C1C-C1-Alkoxy-C1-C1-Alkyl, as defined above, wherein one or more hydrogen atoms are substituted, identically or differently, by one or more halogen atoms.

In particular, the specified halogen atom means PE. The specified halo-C1-C1-Alkoxy-C1-C1-Alkyl means, for example, -CHNaCH»OCE3, -CHNa.CHNaOCNE», -CHNaCHNaOCNoE, -CHNaCH»oOSg2CE», or -CHNeCHgOSNCE:..

The term "C 2 -C 6 -alkenyl" preferably means a linear or branched, monovalent hydrocarbon group containing one or more double bonds and having 2, 3, 4, 5 or 6 carbon atoms, in particular 2 or 3 carbon atoms ("C 2 -C 3 -alkenyl"), it is understood that in the case where said alkenyl contains more than one double bond, then said double bonds may be separated from each other or conjugated to each other. Said alkenyl means, for example, vinyl, allyl, (E)-2-methylvinyl, (2)-2-methylvinyl, homoallyl, (E)-but-2-enyl, (7)-but-2-enyl, (E )-but-1-enyl, (2)-but-1-enyl, pent-4-enyl, (E)-pent-3-enyl, (27)-pent-3-enyl, (E)-pent- 2-enyl, (2)-pent-2-enyl, (E)-pent-1-enyl, (2)-pent-1-enyl, hexo-5-enyl, (E)-hex-4-enyl, (2)-Heco-4-enyl, (E)-Heco-33-enyl, (2)-Heco-3-enyl, (E)-Heco-2-enyl, (2)-Heco-2-enyl, (E)-hex-1-enyl, (2)-heco-1-enyl, isopropenyl, 2-methylprop-2-enyl, 1-methylprop-2-enyl, 2-methylprop-1-enyl, (E)- 1-methylprop-1-enyl, (2D)-1-methylprop-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2- enyl, (E)-2-methylbut-2-enyl, (2)-2-methylbut-2-enyl, (E)-1-methylbut-2-enyl, (2)-1-methylbut-2-enyl, (E)-3-methylbut-1-enyl, (27)-3-methylbut-1-enyl, (E)-2-methylbut-1-enyl, (27)-2-methylbut-1-enyl, (E )-1-methylbut-1-enyl, (2)-1-methylbut-1-enyl, 1,1-dimethylprop-2-enyl, 1-ethylprop-1-enyl, 1-propylvinyl, 1-isopropylvinyl, 4- methylpent-4-enyl,

3-methylpent-4-enyl, 2-methylpent-4-enyl, 1-methylpent-4-enyl, 4-methylpent-3-enyl, (E)-3-methylpent-3-enyl, (2)-3- methylpent-3-enyl, (E)-2-methylpent-3-enyl, (2)-2-methylpent-3-enyl, (E)-1-methylpent-3-enyl, (2)-1-methylpent- 3-enyl, (E)-4-methylpent-2-enyl, (2)-4-methylpent-2-enyl, (E)-3-methylpent-2-enyl, (2)-3-methylpent-2- enyl, (E)-2-methylpent-2-enyl, (2)-2-methylpent-2-enyl, (E)-1-methylpent-2-enyl, (2)-1-methylpent-2-enyl, (E)-4-methylpent-1-enyl, (2)-4-methylpent-1-enyl, (E)-3-methylpent-1-enyl, (2)-3-methylpent-1-enyl, (E )-2-methylpent-1-enyl, (2)-2-methylpent-1-enyl, (E)-1-methylpent-1-enyl, (2)-1-methylpent-1-enyl, 3-ethylbut- 3-enyl, 2-ethylbut-3-enyl, 1-ethylbut-3-enyl, (E)-3-ethylbut-2-enyl, (2)-3-ethylbut-2-enyl, (E)-2- ethylbut-2-enyl, (27)-2-ethylbut-2-enyl, (E)-1-ethylbut-2-enyl, (2)-1-ethylbut-2-enyl, (E)-3-ethylbut- 1-enyl, (27)-3-ethylbut-1-enyl, 2-ethylbut-1-enyl, (E)-1-ethylbut-1-enyl, (2)-1-ethylbut-1-enyl, 2- propylprop-2-enyl, 1-propylprop-2-enyl, 2-isopropylprop-2-enyl, 1-isopropylprop-2-enyl, (E)-2-pr propylprop-1-enyl, (2)-2-propylprop-1-enyl, (E)-1-propylprop-1-enyl, (2D)-1-propylprop-1-enyl, (E)-2-isopropylprop- 1-enyl, (2)-2-isopropylprop-1-enyl, (E)-1-isopropylprop-1-enyl, (2D)-1-isopropylprop-1-enyl, (E)-3,3-dimethylprop- 1-enyl, (2D)-3,3-dimethylprop-1-enyl, 1-11,1-dimethylethyl)ethenyl, buta-1,3-dienyl, penta-1,4-dienyl, hexa-1,5- dienyl or methylhexadienyl. In particular, the specified group means vinyl or allyl.

The term "Co-Cv-alkynyl" preferably means a linear or branched, monovalent hydrocarbon group which contains one or more triple bonds and which contains 2, 3, 4, 5 or 6 carbon atoms, in particular 2 or 3 atoms carbon ("C2-C3-alkynyl"). Said C2-C6-alkynyl means, for example, ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, but-3-ynyl, pent-1-ynyl, pent- 2-ynyl, pent-3-ynyl, pent-4-ynyl, hex-1-ynyl, heco-2-ynyl, hex-3-ynyl, heco-4-ynyl, heco-b5-ynyl, 1-methylprop- 2-ynyl, 2-methylbut-Z-ynyl, 1-methylbut-Z-ynyl, 1-methylbut-2-ynyl,

3-methylbut-1-ynyl, 1-ethylprop-2-ynyl, 3-methylpent-4-ynyl, 2-methylpent-4-ynyl, 1-methylpent-4-ynyl, 2-methylpent-3-ynyl, 1- methylpent-3-ynyl, 4-methylpent-2-ynyl, 1-methylpent-2-ynyl, 4-methylpent-1-ynyl, 3-methylpent-1-ynyl, 2-ethylbut-3-ynyl, 1-ethylbut- 3-ynyl, 1-ethylbut-2-ynyl, 1-propylprop-2-ynyl, 1-isopropylprop-2-ynyl, 2,2-dimethylbut-3-ynyl, 1,1-dimethylbut-3-ynyl, 1, 1-dimethylbut-2-ynyl, or 3,3-dimethylbut-1-ynyl. In particular, the indicated alkynyl means ethynyl, prop-1-ynyl or prop-2-ynyl.

The term "C3-C6-cycloalkyl" means a saturated, monovalent, mono- or bicyclic hydrocarbon ring containing 3, 4, 5 or 6 carbon atoms ("C3-C6-cycloalkyl"). The indicated Sz-

Ceu-cycloalkyl means, for example, a monocyclic hydrocarbon ring, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or a bicyclic hydrocarbon ring.

The term "C4-C6-cycloalkenyl" preferably means a monovalent, mono- or bicyclic hydrocarbon ring containing 4, 5, 6, 7 or 8 carbon atoms and one, two, three or four double bonds, conjugated or not , as the size of the specified cycloalkenyl ring allows.

Said C1-C6-cycloalkenyl means, for example, a monocyclic hydrocarbon ring, for example, cyclobutenyl, cyclopentenyl or cyclohexenyl, or a bicyclic hydrocarbon ring, for example, cyclooctadienyl.

The term "3-7-ene heterocycloalkyl" means a saturated, monovalent, mono- or bicyclic hydrocarbon ring containing 2, 3, 4, 5 or 6 carbon atoms and one or more groups containing heteroatoms selected from C (-O), 0, 5, 5(-0), 5(50)2, MA, where Kg means a hydrogen atom, or Ci-Cv-alkyl- or halo-Ci-Cv-alkyl-; for the indicated heterocycloalkyl, it is possible to attach to the molecule with the help of any of the carbon atoms or, if present, a nitrogen atom. b

In particular, the specified 3-7-membered heterocycloalkyl may contain 2, 3, 4 or 5 carbon atoms, and one or more of the above groups containing heteroatoms ("3-6-membered heterocycloalkyl"), more specifically, the specified heterocycloalkyl may contain 4 or 5 carbon atoms, and one or more of the above groups containing heteroatoms ("5-6-ene heterocycloalkyl").

In particular, without limitation, said heterocycloalkyl may represent a 4-membered ring such as azetidinyl, oxetanyl, or a 5-membered ring such as tetrahydrofuranyl, dioxolinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, pyrrolinyl, or a b-membered ring such as such as tetrahydropyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl or trithianyl, or a 7-membered ring such as diazepanyl, e.g. Optionally, the indicated heterocycloalkyl may be benzocondensed.

Said heterocyclyl may be bicyclic, such as, but not limited to, a 5B,bB-membered ring, e.g., hexahydrocyclopenta|c|Ipyrrol-2(1H)-yl), or a 5,6-membered bicyclic ring, e.g. hexahydropyrrolo(1,2-a|pyrazin-2(1H)-yl.

As noted above, said ring containing a nitrogen atom may be partially unsaturated, i.e., it may contain one or more double bonds, such as, but not limited to, 2,5-dihydro-1H-pyrrolyl, 4H -(1,3,4-hyadiazinyl, 4,5-dihydrooxazolyl or

A4H-P1,4)hyazinyl, for example, or it may be benzo-fused, such as, but not limited to, dihydroisoquinolyl, for example.

The term "4-8 membered heterocycloalkenyl" means an unsaturated, monovalent, mono- or bicyclic hydrocarbon ring containing 4, 5, 6, 7 or 8 carbon atoms and one or more groups containing heteroatoms selected from C( -O), 0, 5, 5(-0), 5(50)»2, MAU, where Kg means a hydrogen atom, or C.i-Cv-alkyl- or halo-Ci-Cv-alkyl-; for the specified heterocycloalkenyl, it is possible to attach to the molecule with the help of any of the carbon atoms or, if present, a nitrogen atom. Examples of the specified heterocycloalkenyl can contain one or more double bonds, for example, 4H-pyranyl, 2H-pyranyl, 3H-diazyrinyl, 2,5-dihydro-1H-pyrrolyl, P1,3|dioxolyl, a4H-P,3, 4 hyadiazinyl, 2,5-dihydrofuranyl, 2,3-dihydrofuranyl, 2,5-dihydrothiophenyl, 2,3-dihydrothiophenyl, 4,5-dihydrooxazolyl or 4H-(/1,4|hthiazinyl, or, may be benzo-condensed .

The term "aryl" preferably means a monovalent, aromatic or partially aromatic, mono- or bi- or tricyclic hydrocarbon ring having 6, 7, 8, 9, 10, 11, 12, 13 or 14 carbon atoms ("Sve-C1i4- -aryl"), in particular, a ring having carbon atoms ("Cv-aryl"), for example, phenyl; or biphenyl, or a ring having 9 carbon atoms ("Ce-aryl"), for example, indanyl or indenyl, or a ring having 10 carbon atoms ("C:io-aryl"), for example, tetralinyl, dihydronaphthyl or naphthyl, or a ring having 13 carbon atoms ("C3-aryl"), eg, fluorenyl, or a ring having 14 carbon atoms, ("C:4"-aryl"), eg, anthranyl.

The term "heteroaryl" preferably means a monovalent, monocyclic-, bicyclic- or tricyclic aromatic ring system having 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 ring atoms ("5-14 membered heteroaryl "), in particular, 5 or 6 or 9 or 10 atoms, and which contains at least one heteroatom, which may be the same or different, said heteroatom being oxygen, nitrogen or sulphur, and in addition, in each case, may be benzofused. In particular, the heteroaryl is selected from the following: thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl, etc., and their benzo derivatives, such as, for example, benzofuranyl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzotriazolyl, indazolyl, indolyl, isoindolyl, etc.; or pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, etc., and their benzo derivatives, such as, for example, quinolinyl, quinazolinyl, isoquinolinyl, etc.; or azocinyl, indolizinyl, purinyl, etc., and their benzo derivatives; or cinolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthypyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl or oxepynyl, etc.

In general, unless otherwise indicated, heteroaryl or heteroarylenyl radicals include all their possible isomeric forms, for example, their positional isomers. Thus, for some illustrative non-limiting Examples, the terms pyridinyl or pyridinylene include pyridin-2-yl, pyridin-2-ylene, pyridin-3-yl, pyridin-3-ylene, pyridin-4-yl, and pyridin-4-ylene; or the term thienyl or thienylene includes thien-2-yl, thien-2-ylene, thien-Z-yl and thien-Z-ylene.

The term "Ci-C6" as used herein, e.g., in the context of the definition of "C1-Cv-alkyl", "C1-Cv-haloalkyl", "Ci-Cv-alkyl", or "Ci-Cv-haloalkyl" means alkyl , having a carbon number of 1-6, i.e., 1, 2, 3, 4, 5, or 6 carbon atoms.It is further understood that (610) the specified term "C1-C" is to be interpreted as any sub-range included in it

for example, C1-C, C2-C5, C3-Cya, C1-C2, C1-C3, C1-Cya4, C1-C, C1-C; in particular, C-C2, C1-C3, C1-Ca4, C1-

C5, Si-Sv; more specifically, Si-Sa; in the case of "Ci-Cv-haloalkyl" or "Ci-Cv-haloalkyl", more specifically, C1-C".

Similarly, as used herein, the term "C 2 -C 6 , as used herein, for example, in the context of the definition of "C 2 -C 6 -alkenyl" and "C 6 -C 6 -alkynyl", means alkenyl or alkynyl having the number of atoms carbons 2-6, i.e. 2, 3, 4, 5 or 6 carbon atoms.It is further to be understood that the specified term "C2-Ce" is to be interpreted as any sub-range included therein, e.g. C2-Cv, Sz-Sv, Sz-S4, Sb2-Sz, bo-S4, Sbo-Sv, in particular, S2-Sz.

Also, as used herein, the term "C 3 -C 6 ", as used herein, for example, in the context of the definition of "C 3 -C 6 cycloalkyl", means cycloalkyl having 3-6 carbon atoms, i.e., 3, 4, 5 or 6 carbon atoms.It is further to be understood that the term "C3-C6" is to be interpreted as any sub-range included therein, e.g.

Sz-Sv, Sa-Sv, Sz-Sv, Sz-Sa, Sa-Sv, S5-Sv; zOkrema, Sz-Sv.

The term "substituted" means that one or more hydrogens on the specified atom are replaced by the specified group, provided that the normal valence of the specified atoms under the specified conditions is not exceeded, and that the substitution results in a stable compound. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.

The term "optionally substituted" means optional substitution with certain groups, radicals or residues.

A ring system substituent means a substituent attached to an aromatic or non-aromatic ring system that, for example, replaces a free hydrogen on the ring system.

As used herein, the term "leaving group" refers to an atom or group of atoms substituted in a chemical reaction as a stable species by withdrawing attached electrons. Preferably, the leaving group is selected from the following: a group containing: halo, in particular chlorine, bromine or iodine, methanesulfonyloxy, p-toluenesulfonyloxy, trifluoromethanesulfonyloxy, popafluorobutanesulfonyloxy, (4-bromo-benzene)sulfonyloxy, (4-nitro-benzene) sulfonyloxy, (2H-nitro-benzene)-sulfonyloxy, (4-isopropyl-benzene)sulfonyloxy, (2,4,6-tri-isopropyl-benzene)-sulfonyloxy, (2,4,6-trimethyl-benzene)sulfonyloxy, (4-butyl-benzene)sulfonyloxy, benzenesulfonyloxy and (4-methoxy-benzene)sulfonyloxy.

As specified in this document, the term "one or more times", for example, when defining the substituents of a compound of the general formula of this invention, means "one, two, three, four or five times, in particular, one, two, three or four times , more specifically, once, twice or three times, even more specifically, once or twice".

When the plural terms compounds, salts, polymorphs, hydrates, solvates, etc. are used, this also means a single compound, salt, polymorph, isomer, hydrate, solvate, etc.

By "stable compound" or "stable structure" is meant a compound that is capable of withstanding isolation to a certain degree of purity from a reaction mixture and formation into an effective therapeutic agent.

According to the first aspect, the present invention relates to a compound of the general formula I: on KN as in M

AND

Eat where:

A means v'z vya vya

N

4 years

Y V x M « o /y M // M or or d'z x xx vo rya 4 years

A NM ve or ; where " indicates the place of attachment of the indicated groups to the molecule; 2 means -C(-O)M(H)B2 or -C(-5)M(H)B, or a group selected from

ZE t3buOh M stream

Hn Hn MN M and M Ya

MI MI-- MI-- 2 2 2 2 2 M M

V V A N i N z z z z z z ; V Y ;

MU m tm DY tn ran - - MN M on ne sha our

M 2 2 " ! -M 2

Н в в -М я А where " indicates the place of attachment of the indicated groups to the molecule;

IN? means a hydrogen atom, or C.i-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bev)M-C-Cv-alkyl, HO-C1-Cv-alkyl, -C1-Cv-alkyl-"CM . where the indicated C3-Cv-cycloalkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 groups selected from the following: halogen, -OH, -CM, C1-Cv-alkyl, Ci-Cv- alkoxy-, halo-C1-

St-alkyl-;

BZ means a hydrogen atom or a halogen atom, or -CM, C1-C8-alkyl, C1-C8-alkyl, -(CHg)t-Seg-C8-alkenyl, /-(CHg)t-C4-C8-cycloalkenyl, /-(CHn)t-C2-Cv-alkynyl, /-«(«CHn)t-C3-Cv-cycloalkyl, -(CHe)t-(3-7-membered heterocycloalkyl), -(CHe)t -(4-8-membered heterocycloalkenyl), aryl-C1-Cv-alkyl, heteroaryl-C:-Cv-alkyl, halo-C1-Cv-alkyl, Bea(Bev»)M-C1-Cv-alkyl, halo-C1-Cv-Alkoxy-C1-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cv-alkenyl-, Ca-Cv-cycloalkenyl-, C2-

C1-alkynyl-, aryl-, -Ci-Ci-alkyl-aryl, -C1-Ci-alkyl-heteroaryl, heteroaryl-, Ci-Ci-alkyl-xX-, 20. -X-A(CHn)t-C2 -Cv-alkenyl, -X-(CHg)t-Ca-Cv-cycloalkenyl, -X-(CHg)t-C2-Cv-alkynyl, -X-(CHg)t-C3-Cv-cycloalkyl, -X- (CHn)t-(3-7-membered heterocycloalkyl), -X-(CHn)t-(4-8-membered heterocycloalkenyl), aryl-X-, heteroaryl-Xx-, -C(-0)H5 . С(-О)Н8е, -ОН85, -5855, -5(-0)НЭ, -5(-0)2Н88, -5(-0)(-М Аа)», -5(-0)2М( Bc) Ves, -5-(CHg)n-M(Bea)Be" or -5-(CHg)p-(3-7-membered heterocycloalkyl); where Ci-Cv-alkyl, Ci-Cv-alkyl, -(CNeg)t-Cg2-Cv-alkenyl, -(CHg)t-C2-Cv-alkynyl, -(CNeg)t-C3-Cv-cycloalkyl are indicated , aryl-C:-Cv-alkyl, heteroaryl-C:-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, Cg-Cv-alkenyl-, C4--Cv-cycloalkenyl-, C2 -Cv-alkynyl-, aryl-, C1-Cv-alkyl-X-, /-X-(CHeg)t-Cg-Cv-alkenyl, /-X-(CHg)t-Ca-Cv-cycloalkenyl, /- X-(CHn)t-C2-Cv-alkynyl, -X-(CHn)t-C3-Cn-cycloalkyl, -X-(CHn)t-(3-7-membered heterocycloalkyl), -X-( CHn)t-(4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-x-, -C1-C6-alkyl-aryl, -C1-C6-alkyl-heteroaryl or heteroaryl- is optionally substituted, identical or differently, 1, 2, 3, 4 or 5 KE" groups; da, DV, des, DYA mean, independently of each other, hydrogen or a halogen atom, or -CM,

Ci-Cv-alkyl, Ci-Cv-alkoxy-, halo-Ci-Cv-alkyl, Bea(Bev)M-C1-Cv-alkyl, HO-C:-Cv-alkyl, C1-Cv-

B Alkoxy-Ci-Cv-alkyl, halo-C1-Cv-Alkoxy-C1-Cv-alkyl, -C(-O)H8E, -C(-O)M(H) NIA, -C(-O)M (Ве) de», -б(-00-Н5, -М(Вба)ВНЯ», 0 -МО», -МЖШХН)С(-О)НЯ, 0 -М(НеС(-0)Н8Я, 0 - Ш(Н)С(-О)М(Аг) Бе», -М(Нбг)С(-О)М(Няа)веЯ» -М(Н)С(-О)ОВЯ, 0 -М(Не) C(-0)ONYA, 0 -M(H)B(-O)BYA, 0 -M(He(-O) 88, -M(H)B(-0)28Y, -M(Neg)5( -0)286, -М-5(-0О)(Нба)ВАей -ОНЯ, -О(С0-0)Н85, -О(С-О)М(Нег)Бе», -0(С0-00ОН5, -51386, -5(-0)Н5, -5(-0О)М(Н)АН5, -5(-0О)М(Нба)ВНе, -5(-0285, -5(-0)2М(Н )Nva, 10. -5(-0)2M(Nea)Ve, -5(-0)(-MNes)Ve;

AV? means a hydrogen atom, or Ci-Cv-alkyl, -(CHn)n-C2-Cn-alkenyl, -(CHn)p-C2-Cn-alkynyl, -(CHn)t-C3-Cn-cycloalkyl, -(CnHg )t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bei)M-C1-Cv-alkyl, HO- S.:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered 15 heterocycloalkyl, Cge-Cv-alkenyl-, C4-Cv -cycloalkenyl-, Cg-Cv-alkynyl-aryl- or heteroaryl-; where Ci-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t -(3-7-ene heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(de»)M-C1-Cv-alkyl, HO- C.1-Cv-alkyl, -C1-Cv-alkyl-CM, C-Cv-Alkoxy-C:-Cv-alkyl, halo-C1-20 Cv-Alkoxy-C1-Cv-alkyl, C3-Cv-cycloalkyl , 3-7-ene heterocycloalkyl, C4-Cv-cycloalkenyl-, aryl- or heteroaryl- is optionally substituted, identically or differently, by 1, 2, 3 or 4 KV groups;

Ve, Vba, dDBB, Des mean, independently of each other, a hydrogen atom, or Ci-Cv-alkyl, HO-C-

C1-alkyl, C3-C8-cycloalkyl, C2-C8-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, 25 aryl-C:i-C8-alkyl- or heteroaryl-C:-C8 -alkyl-;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bea(Bev)M-Ci-Cv-alkyl,, HO -C.:-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-О)НЕ, -ФШ(-ОМ(Н)АЯа, -С(-О)М( Vta)Ve, -C(-0)0-86, -M(Vba)Ve", -MO", -M(H)C(-O)H8e, -M(Neg)C(-O)8e, 30 00 -МЩ(Н)С(-О)М(Аа)Ве, "(Не С(-О)М(Ата)Ве, -М(Н)С(-OOВе, -М(Не)С(- ООНВе, -МЩ(Н)(-О Ne, -М(Нбг)5(-0)Н8Я, -М(Н)Б(-О0)28?, -М(Нбг)5(-0)2НЯ, - М-5(-О)(Н)ВА -ОВ8б, 0 -О(0-О)В8е, -О(С-О)М(Нба)неЯ» -О(С0-0)ОНе, -52я58, - 5(-0)Н5, -5(-0)М(Н)Н5, -5(-0)М(Нба)Ве, -5(-0)2Н56, -5(-0)2М(Н) No . . are in the ortho position to each other on the aryl or heteroaryl ring, the indicated 2 KE" groups together form a bridge: 40 "О(Снгаг5о "О(СнНаУО", "МН(С(-ОУМН)", where " means the place of attachment of the indicated aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl,

Vba(de)M-Si-Cv-alkyl, HO-C:-Cv-alkyl, Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, C2-Cv -alkenyl-, C3-7/--ene heterocycloalkyl, aryl-, heteroaryl-, -0(-0)РНЭ, 45 -Щ(-ОМ(Н)Нба, -С(-ОО)М(Нба)Бе» . С(-О)М(На)Нев, -М(Нес)С(-О)М(Аба)Нев, -М(Н)С(-О0)ОНе, -М(Не)С(-0)ОНе , -M(H)B(-O)He, -M(Nbs)5(-0)H5, -M(H)B(-0)285, -M(Nes)B(-0)2Nb, - М-5(-О)(Нба)НЯВ -0Нб 0 -О(0-0)Н, -О(С-О)М(Нба)неЯ» -О(С0-0)ОНе, -52я58, -5 (-0)H5, -5(-0)M(H)H5, -5(-0)M(Nba)He, -5(-0)2H56, -(-0)2MSH(H)He, - 55-0)2M(a)Ve, -5(-0)(-M Ag) or -5(-0)2-(3-7-membered heterocycloalkyl); 50 where the indicated 3-7-membered heterocycloalkyl- or heteroaryl- is optionally substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyl-; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5;

X stands for 5(:O)r, O, HAS, Svbade or C-Srvade: and 55 r means an integer 0, 1 or 2.

As stated above, A means action

N

, in? . M / M 4s vya 7 d or or 4a

A vya and o) " in: / M 4s - M 4s in and 4r 4r 92 A NM or ; where " indicates the place of attachment of the specified groups to the molecules.

In the preferred embodiment, A stands for vya

And in? at 7 there are 5.

In another preferred embodiment, A stands for vya

N

. M / M is blowing wd? NM v2

In another preferred embodiment, the invention relates to a compound of formula I, above, where A is selected from the group consisting of:

And And And

M M (Fi M SN. sn. o sn, c) Y sn Z (c) Y 1 (0) z z z z h N z H

And I

M. OSNz M

SN, (c) and SN, Z

As indicated above, K2 means a hydrogen atom, or Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kea(Ve)M-O1-

C1-alkyl, HO-C1-Cv-alkyl, -C1-Cv-alkyl-СМ, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, Co-Cv -alkenyl-, C1-C8-alkynyl- or C3-C8-cycloalkyl-; where the indicated C3-Cv-cycloalkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 groups selected from the following: halogen, -OH, -CM, C1-Cv-alkyl, Ci-Cv- alkoxy-, halo-C1-

St-alkyl-.

In a preferred embodiment, the invention relates to a compound of formula Y, where:

IN? means C3-C6-cycloalkyl-; where the indicated C3-Cv-cycloalkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 groups selected from the following: halogen, -OH, -CM, Ci-Cv-alkyl, Ci-Cv- alkoxy-, halo-C1-

St-alkyl-.

In another preferred embodiment, the invention relates to a compound of formula Y, where:

B2 means C3-C6-cycloalkyl-; where the indicated C3-C8-cycloalkyl- is optionally substituted, identically or differently, by 1, 2 or C groups selected from: halogen, -OH, -CM, -C1-C8-alkyl, -C1-C8-alkyl .

Preferably, C3-C6-cycloalkyl- means cyclopropyl-.

In another preferred embodiment, the invention relates to a compound of formula Y, where:

IN? means C3-C6-cycloalkyl-; where the indicated C3-C3-cycloalkyl- is optionally substituted, identically or differently, by 1 or 2 groups selected from: -CM, -C1-C3-alkyl, -C1-C3-alkyl.

Preferably, C3-C6-cycloalkyl- means cyclopropyl-.

In another preferred embodiment, the invention relates to a compound of formula Y, where:

IN? means cyclopropyl-; where the specified cyclopropyl- is optionally substituted, identically or differently, by 1, 2, C or 4 groups selected from: halogen, -OH, -CM, -C1-Cv-alkyl, -C1-Cv- alkoxy.

In another preferred embodiment, the invention relates to a compound of formula Y, where:

IN? means cyclopropyl-; where the indicated cyclopropyl- is optionally substituted, identically or differently, by 1 or 2 groups selected from: halogen, -OH, -CM, -C1-Cv-alkyl, -C1-Cv-alkyl.

In another preferred embodiment, the invention relates to a compound of formula Y, where:

IN? means cyclopropyl-; where the specified cyclopropyl- is substituted, identically or differently, by 1 or 2 groups selected from: halogen, -CM, -C1-C3-alkyl, -C1-C3-alkyl.

In another preferred embodiment, the invention relates to a compound of formula Y, where:

B2 means a halo-C:-C1-alkyl-.

In another preferred embodiment, the invention relates to a compound of formula Y, where:

B2 means C.:-Cv-alkyl-; where the indicated C:i-Cv-alkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 groups selected from: halogen, -OH, -CM, Ci-Cv-alkoxych-.

In another preferred embodiment, the invention relates to a compound of formula Y, where:

Bg means Ci-Ca4-alkyl-; where the indicated C1-Cα-alkyl- is optionally substituted, identically or differently, with 1, 2 or C groups selected from: halogen, -OH, -CM, -C1-C-alkoxy.

In another preferred embodiment, the invention relates to a compound of formula Y, where:

Bg2 means a methyl- or ethyl-; where the indicated methyl- or ethyl- is optionally substituted, identically or differently, 1, 2 or

With groups selected from: halogen, -OH, -CM.

In another preferred embodiment, the invention relates to a compound of formula Y, where:

IN? means CH3 or CeH5.

In another preferred embodiment, the invention relates to a compound of formula Y, where:

B2 means C.:-C3-alkyl-;

where the indicated C1-C3-alkyl- is optionally substituted, identically or differently, with 1, 2 or C groups selected from: halogen, -OH, -CM, -C1-C3- alkoxy.

The invention relates to a compound of formula I, where:

BZ means a hydrogen atom or a halogen atom, or -CM, C1-Cv-alkyl, Ci-Cv-alkyl-, -(CHg)t-Seg-

C-alkenyl, /-(CHg)t-C4-Cv-cycloalkenyl, /-(CHg)t-C2-Cv-alkynyl, /-«("CHeg)t-C3-Cv-cycloalkyl, -(CHe)t -(3-7-membered heterocycloalkyl), -(CNeg)t-(4-8-membered heterocycloalkenyl), aryl-C1-C1-alkyl, heteroaryl-C:-C1-alkyl, halo-C1- C1-alkyl, Kba(Bei)M-C1-C1-alkyl, halo-C1-C1-alkyl-C1-C1-alkyl, C3-C8-cycloalkyl, 3-7-membered heterocycloalkyl, C2-C8-alkenyl-, Ca-Cv-cycloalkenyl-, C2-

C1-C8-alkynyl-, aryl-, -C1-C8-alkyl-aryl, -C1-C8-alkyl-heteroaryl, heteroaryl-, C1-C8-alkyl-xX-, -X-(CHg)t-C2-Cv- alkenyl, -X-(CHg)t-Ca-Cv-cycloalkenyl, -X-(CHg)t-C2-Cv-alkynyl, -X-(CHg)t-C3-Cv-cycloalkyl, -X-(CHg) t-(3-7-membered heterocycloalkyl), -X-(CHg)t-(4-8-membered heterocycloalkenyl), aryl-Xx-, heteroaryl-Xx-, -C(-0)H8E, -C (-О)М(Н)НяТа, /-С(-О)М(Веа)Ве», -6(-0)0-Не, -М(Вба)Ве, -MO», -Щ(Н) C(-O)He, -OHe, -5185, -5(-0)H85, -5(-0)286, -5(--0)(-MAva)BeB, 15. -5(-0) 2M(B)rve, -5-(CHg)n-M(B92)Be" or -5-(CHg)p-(3-7-membered heterocycloalkyl); where C:i-Cv-alkyl, Ci-Cv-alkyl, -(CHg)t-C2-Cv-alkenyl, -(CHg)t-C2-Cv-alkynyl, -(CH2g)t-C3-Cv are indicated -cycloalkyl, aryl-Ci-Cv-alkyl, heteroaryl-C1-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, Cg-Cv-alkenyl-, C"-Cv-cycloalkenyl-, Cg-Cv -alkynyl-, aryl-, C1-Cv-alkyl-X-, /-X-(CHg)t-C2-Cv-alkenyl, /-X-(CHeg)t-Ca-Cv-cycloalkenyl, /-X- (CNeg)t-C2-Cv-alkynyl, 20. -X-A(CNeo)t-C3-Cv-cycloalkyl, -X-(CHg)t-(3-7-membered heterocycloalkyl), -X- (CHn)t-(4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-x-, -C1-C6-alkyl-aryl, -C1-C6-alkyl-heteroaryl or heteroaryl- is optionally substituted, identically or differently, in 1, 2, 3, 4 or 5 KE" groups.

In a preferred embodiment, the invention relates to a compound of formula I, above, wherein:

VZ means

C-Cv-alkyl-X-, -X-(CHeg)t-C2-Cv-alkenyl, /-X-(CHg)t-C4-Cv-cycloalkenyl, -X-(CHg)t-C2-Cv- alkynyl, -X-(CH2e)t-C3-Cv-cycloalkyl, -X-(CH2g)t-(3-7-membered heterocycloalkyl), -X-(CH2g)t-(4-8-membered heterocycloalkenyl) , aryl-, heteroaryl-, aryl-X or heteroaryl-x-; where indicated /Ci-Cv-alkyl-X-, -X-(CHg)t-C2-Cv-alkenyl, /-X-(CHg)t-C4-Cv-cycloalkenyl, -X-(CHg)t-C2 -C-alkynyl, -X-(CHg)t-C3-Cv-cycloalkyl, -X-(CHg)t-(3-7-ene heterocycloalkyl), -X-(CHg)t-(4-8- -lene heterocycloalkenyl), aryl-, heteroaryl-, aryl-X or heteroaryl-X is optionally substituted, identically or differently, by 1, 2, 3 or 4 B" groups.

In another preferred embodiment, the invention relates to a compound of formula I, above, wherein:

BZ means a hydrogen atom or a halogen atom, or Ci-Cv-Alkoxy-, -"(CHe)t-C2-Cv-alkenyl, aryl-, aryl-Xx-, heteroaryl-X-, heteroaryl-, -(CHe)t -C4-Cv-cycloalkenyl, -(CH2e)t-C3-Cv-cycloalkyl, -(CHe)t-(4-8-membered heterocycloalkenyl), aryl-, -C(-O)M(H)Aba . -membered heterocycloalkyl); where the specified C1-C1-alkoxy-, aryl-, aryl-Xx-, heteroaryl-X or heteroaryl- is optionally substituted, identically or differently, by 1, 2, 3, 4 or 5 KE" in groups

In another preferred embodiment, the invention relates to a compound of formula I, above, wherein:

BZ means a hydrogen atom or a halogen atom, or -(CHg)t-C2-Cv-alkenyl, -(CHg)t-Ca-Cv- cycloalkenyl -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (4-Y--ene heterocycloalkenyl), aryl-, heteroaryl-, aryl-Xx-, heteroaryl-x-, -С(-О)1М(Н)НТ, -085, -585, -5(-0) H85, -5(-O)2H6, -5-(CHn)n-M(Veba)Be" or -5-(CH2n)p-(3-7-ene heterocycloalkyl); where the specified aryl-, aryl-x-, heteroaryl-X or heteroaryl- is optionally substituted, identically or differently, by 1, 2, 3 or 4 K" groups.

In another preferred embodiment, the invention relates to a compound of formula I, above, wherein:

BZ stands for aryl-, -C1-C6-alkyl-aryl, aryl-x-, heteroaryl-Xx-, heteroaryl-, -C1-C6-alkyl-heteroaryl, heteroaryl-dichloro; where the specified aryl-, aryl-x-, heteroaryl-xX-, heteroaryl-, -C1-Cv-alkyl-aryl or -C1-Cv-alkyl-heteroaryl-dgoyr is optionally substituted, identically or differently, 1, 2, Z or 4 V" groups.

In another preferred embodiment, the invention relates to a compound of formula I, above, wherein:

BZ means substituted or unsubstituted aryl-x-, or substituted or unsubstituted heteroaryl-x-.

Preferred aryl-X means phenyl-x-.

Preferred heteroaryl-X means quinolinyl-X-, pyridyl-X-, thienyl-X-, pyrazinyl-X-, imidazyl-X-, triazyl-X- and pyrazyl-X-.

VZ is optionally substituted, identically or differently, by 1, 2, 3, 4 or 5 KE" groups.

In a preferred embodiment, the invention relates to a compound of formula I, where KZ is optionally substituted, identically or differently, by 1 or 2 KE" groups.

In another preferred embodiment, the invention relates to a compound of formula I, wherein the KZ is selected from the group consisting of:

E not (in) rf | what is

In SN, in SN, SN, | AND

What)

CH,

But no

Oh oh oh CH» oh CH»

W o o o o o o o o o o o o o o o o o o o

Soo Phi what Phii

B is not a dream. SM o o" sn o

Y Z o o NO (F) (c) po u sn, sn, (c) o (c)

IS

(in)

X te Z ns sn, sn. but o" z z E z z sn,

IS

E o CH" E o"

Oh, no, no

E re; not

GO) J

SNU o E o E si E o" SI E o o "o o o dk Zh

E s y

E E SI and Nis

Oh and oh"

ХА, , ой «Ж, и

IJ

Mn, Mn, E ns "MN

Sh

MN about" NS

MN about Co.; SN. "MN "MN "MN "MN "MN no no oh no no " MN yes MN "MN " MN

Phi Su su" in sn ns ne o7 Z Z zo Z zo

Mn "MN "Mn I MN i MN "MN no 7 7 E no re no MN, he E E Us no "MN /e still "MN "MN " MN no no E shchen

СН is E ono "МН | | eМН | em "МН "МН "Мн

IS

IS

E E OS SI E E

"Mn "Mn | "Mn "Mn E SI " MN p

IS

E E E E SI E

"Mn | | "Mn

E "MN" MN wouldn't sit. SHY E SN "MN MN he he not E I

MN t city of SN. What?

"MN x MN MN MN sn, SN. E sn,

SI E SNU E

M. H

What

He E eh S | In x xx | ro n.s MN NM M i Ts MN Vii 2

In Zh

SN, o" he o) o) i i " MN

MN o) zh zh zh zh

MN

MN MN xx xx | From where eh | y: MS YAM 27 o

M - th 2 M 4 E E NS; 87 87

With in 7 ns o and re ro) sn, not sn, not E zhk sn, not 5 E E 57 СН» E 5 zhk

Not with 87 87 5

R sn, E

E E

E CH; E E E

57 57 57 vd7 nm

E E E E E

87 v7 ono 8' v7 8 onov" on sn, t) on on si v7 V o (v) oh o z

SN, in oh zv, Hv o

T 5 sn. ns E E in"

M--M vah - A / X | chX her --x her x

Mom 587

M 1/ M - w w w still shk N M 5 4 8 4 о о х о 11 и х ех M ху M

S. fi S x A sh i;

/Uu M and M i

M. Zh

Mn zo U, / ХУ , / в"

And MMdy | m" Z m Z ns o СН» Н N - o Ж

Go) And

So, M

M A k (c); (in);

Her Shk S) rya rya M

N

The invention relates to the compound of formula I, above, where: da, DV, des, DYA mean, independently of each other, hydrogen or a halogen atom, or -CM,

Ci-Cv-alkyl, Ci-Cv-Alkoxy-, halo-Ci-Cv-Alkyl, Kba(Nev)M-C1-Cv-Alkyl, HO-C1-Cv-Alkyl, Ci-Cv-Alkoxy-C1-Cv -alkyl, halo-C1-Cv-Alkoxy-C1-Cv-alkyl, -C(-O)H8E, -C(-O)M(H)Aea, -C(-O)M(Nea)Be", -Ш-0)0-НЭ, -М(Ввба) de, -MO», -ЖНС(-О)Не, -М(Нбе)С(-О)Н5, -МН)С(-О)М( ea) de", -M(Nbs)С(-О)М(Аба)не, -МЩ(Н)С(-О0О0ОНб, 0 -М(Нб)С(-0)ОНб, 0 -М(Н) Б(-О)НЯ, 0 -М(Нег)Б(-О) No, -М(Н)Б(-0)28Н5, -М(Нбс)5(-0)286, -М-5(- 0)(Нба)Не», -0Нб, -0(0-0)Н8б, -О(С-О)М(Бба)деБ, -0(С0-00ОН5, -51386, -5(-0)Н5 . Vza)Ve, -5(-03-M Ag).

In a preferred embodiment, the invention relates to a compound of formula I, above, wherein:

Vl, De, ДЯ means a hydrogen atom, and

AND?" means a hydrogen atom, a halogen atom, or a Ci-Cv-alkyl-.

In another preferred embodiment, the invention relates to a compound of formula I, above, wherein:

В, Дт, ДЯ means a hydrogen atom, and

Yes means a halogen atom, C-Cv-alkyl, -ОНе, -О(С-0)Не, -0(С0-О)М(Неа)Бе», -0(С-О)ОНУ, -

ЗА, -5(-0)Н8е, -Б(--ОМ (НН, -(-О)М(Аеа)Ве, -5(-0)285, -5(-0)2М(Н) Aа, -55-0)2M(Nba) Ne" or -(-0X-M As),

In another preferred embodiment, the invention relates to a compound of formula I, above, wherein:

Ve, De, Du means a hydrogen atom, and De: means a halogen atom, Ci-Cv-alkyl- or -ONE.

In another preferred embodiment, the invention relates to a compound of formula I, above, where: da, B, where: and BZ are, independently of each other, hydrogen or a halogen atom, or -CM, -OH, Ci-Cv-alkyl, Si -Cv-Alkoxy-, halo-C1-Cv-alkyl, halo-C1-Cv-Alkoxy-, Nea(Be)M-C1-Cv-Alkyl, HO-Ci-Cv-Alkyl, MCOS-C1-Cv-Alkyl , C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl-; provided that at least one of the groups KE" and Ks is not a hydrogen atom.

In another preferred embodiment of the present invention, Ka and BK are, independently of each other, hydrogen or a halogen atom, or -CM, Ci-Cv-alkyl, Ci-Cv-alkyl-, halo-C1-Cv-alkyl- or halo -C1-Cv-Alkoxy-.

In another preferred embodiment of the present invention, Ka and B are, independently of each other, hydrogen or a halogen atom, or Ci-Cv-alkyl, Ci-Cv-alkyl-, or halo-C1-Cv-alkyl-.

In another preferred embodiment of the present invention, B": and BZ are hydrogen.

In another preferred embodiment of the present invention, B" and Bc mean, independently of each other, hydrogen or a halogen atom, or -CM, -OH, Ci-Cv-alkyl, Ci-Cv-alkyl-; provided that at least one from VE groups"? and B: is not a hydrogen atom.

In another preferred embodiment of this invention B? and Bc are independently hydrogen or C:-C1-alkyl-; provided that at least one of the groups E?? and B is not a hydrogen atom.

In another preferred embodiment of the present invention, B" and K are independently of each other, hydrogen or C:1-C4-alkyl-; provided that at least one of the groups E? and B is not a hydrogen atom.

In another preferred embodiment of the present invention, one of the groups 25 and c represents a hydrogen atom, while the other represents a group selected from: halo-, -CM, -OH, Ci-Cv-alkyl, Ci--Cv-Alkoxy- , halo-C1-Cv-alkyl, halo-C1-Cv-alkoxy-, Nea(Be»)M-C1-Cv-alkyl, HO-C1-Cv-alkyl, MO-C1-Cv-alkyl, C1-

C1-C1-Alkoxy-C:-C1-C1-Alkyl- and Halo-C1-C1-C1-Alkoxy-C1-C1-C1-Alkyl-.

In another preferred embodiment of the present invention, one of the groups KE" and Bc represents a hydrogen atom, while the other represents a group selected from: halo-, -CM, -OH, Ci-Cv-alkyl, and Ci-Cv- Alkoxy-.

In another preferred embodiment of the present invention, either: B5-C1-C-alkyl- and B": x hydrogen; or: B" - hydrogen and Bs-C1-C-alkyl-.

In another preferred embodiment, the invention relates to a compound of formula I, wherein:

A means i and сн, where " indicates the place of attachment of the specified groups to the molecule; and 2 means -С(-О)М(Н)В2 or -С(-5)М(Н)В.

Preferably 7 means -С(-ОМ(Н)В.

In another preferred embodiment, the invention relates to a compound of formula I, above, where the following compounds (separately described in M/O 2011/013729A1) are excluded:

MN MN

0 -M and -M

Me ch rya and M Y gas --k M M M

N N

Me

Me Me (c) (c)

NM NM

The invention relates to a compound of formula I, above, where:

IN? means a hydrogen atom, or Ci-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CnHg )t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl,

heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bei)M-C1-Cv-alkyl, HO-C.:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cv-alkenyl-, C4-Cv- cycloalkenyl-, C1-C8-alkynyl-, aryl- or heteroaryl-; where Ci-Cv-alkyl, -(CHg)n-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-membered heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-C:-Cv-alkyl, halo-Ci-Cv-alkyl, Kea(Beb)M-C1-Cv-alkyl,, HO -C1-Cv-alkyl, -C1-Cv-alkyl-CM, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-Ci-Cv-Alkoxy-C1-Cv-Alkyl, C3-Cv-cycloalkyl, 3- 7-membered heterocycloalkyl, Са4-Св- cycloalkenyl-, aryl- or heteroaryl- is optionally substituted, identically or differently, by 1, 2, 3 or 4 KZ groups.

In a preferred embodiment, the invention relates to a compound of formula I, above, wherein:

B" means a hydrogen atom, or C:1-C8-alkyl, -(CHg)t-(3-7-membered heterocycloalkyl), aryl- or heteroaryl-; where the indicated C1-C8-alkyl, -(CH8)t-(3-7--ene heterocycloalkyl), aryl- or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 8 groups.

In another preferred embodiment, the invention relates to a compound of formula I, above, wherein:

B means C1-C6-alkyl, -(CH8)t-(3-7-membered heterocycloalkyl), aryl- or heteroaryl; where the indicated C1-C8-alkyl, -(CH3)t-(3-7--lene heterocycloalkyl), aryl-, heteroaryl is optionally substituted, identically or differently, by 1, 2, 3 or 4 KZ groups.

In another preferred embodiment, the invention relates to a compound of formula I, where KK? selected from the groups consisting of:

Н, (Снз2гсСн-, СНе»г-, СЕз-, СЕз-СНе-, СЕз-СНо-СНе-, СЕз-СН(ОН)-, HO-СНе-, HO-С(СнНз)2г-, nОо- Фс(Снз2гсСне-, НОо-СнНо-СН(ОН)-, НЗОС-ОО-СНе-,. NaM-СНе-СНе-, NaM-С(СН3)2г-, (Снз)24М-СНе-, (Снз )гмМ-Сна-СнНе-, (Снз)2гмМ-СнНо-СнНо-СНе-, (Снз)2гМ-С(СнНз) 2-, НЗОо-5(-0)2-СНЭ-,

НЗОо-5(-0)2-СН»-СНе-, НО-5(-0)2-СНе-, НО-5(-0)2-СНо-СнНе-, MO-СНе-, НЗОС-С( -0)-M(H)-CH",

NZO-F(-0)-M(H)-СНо-СНе-, Ngm-С(-0)-СнНе-, (Снз)2гмМ-С(-0)-СнНе-,

НЗо-М(Н)-С(-0)-Ш(СН3)-СНе-СнНе-, (6) (c) І Оу / о 5 5 8

F F F F F F F F F:

N

(c) (c) With "5 M N

AOS

M M M x sn, sn, sn, sn, (in) 5 o o (C Z

N

Mshe S ) S Z M I nina nom (c) sn, re sn, sn, but not SN. well well

E E z z z m-k z

BE Iii i- M He

M M M M-- M xx '"- '"- - / M u // u / Y M MN

M M A Men, Kk sn,

From , , , , , , I

In another preferred embodiment, in the compound of formula Y, above,

B" means 1,1,1-trifluoroethyl.

The invention relates to a compound of formula I, above, where:

VU, Vba db and c mean, independently of each other, a hydrogen atom or Ci-Cv-alkyl,

HO-Ci-Cv-alkyl, C3-Cv-cycloalkyl, Co-Cv-alkenyl-, C-7-membered heterocycloalkyl, aryl, heteroaryl-, aryl-C1-Cv-alkyl- or heteroaryl-C1-Cv-alkyl- .

In a preferred embodiment, the invention relates to a compound of formula I, above, wherein:

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C--

C1-alkyl, C3-C6-cycloalkyl- or aryl.

In another preferred embodiment, the invention relates to a compound of formula I, where

Ve, Dba, DB and res mean, independently of each other, a hydrogen atom or Ci-Cv-alkyl-.

The invention relates to a compound of formula I, above, where:

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kea(Nev)M-C1-Cv-alkyl, HO- C:1-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-О)НЕ, -ФШ(-ОМ(Н)АЯа, -С(-О)М( Vta)Ve, -C(-0)0-86, -M(Vba)Ve", -MO", -M(H)C(-O)H8e, -M(Neg)C(-O)8e, -МН)С(-О)М(На)Ве, "(Не С(-О)М(Ата)Ве, -М(Н)С(-О)ОВе, -М(Не)С(-ООНВе, -МЩ(Н)(-ОНе, -М(Нбг)5(-0)Н8Я, -М(Н)Б(-О0)28?, -М(Нбг)5(-0)2НА, -М-5 (-О)(Н)ВА -ОВ8б, 0 -О(0-О)В8е, -О(С-О)М(Неа)ВЯ» -О(0-0)0ОН?, -586, -5( -0)Н88, -5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, 20. -5(-0)2М(Н)Не , -55-0)2M(НЯ2)ВАЭ" or -5(-0-МНег)Ве; where the specified C:1-C8- alkoxy-, aryl- or heteroaryl is optionally substituted, identically or differently, 1 , 2 or 3 C-Cv-alkyl, C-Cv-alkyl-, halo-C1-Cv-alkyl-, -C(-0)0-H5 or -OH groups; or when 2 KK" groups are in the ortho position to each other on an aryl or heteroaryl ring, the indicated 2 KE" groups together form a bridge: "О(СнггЬО" "СОСНУ" "МН(С(-О))МН", where " means the place of attachment to the indicated aryl- or heteroaryl- rings

In a preferred embodiment, the invention relates to a compound of formula I, where B" means hydrogen or a halogen atom, or HO-, -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl, Bea( Bev) M-C1-Cv- alkyl, HO-C1-Cv-alkyl, H2M-Ci-Cv-alkyl, C-Cv-alukoxy-C1-Cv-alkyl, halo-C1-Cv-alkyl-C1-Cv- alkyl, Co-Cv-alkenyl, 3-7--ene heterocycloalkyl, aryl-, heteroaryl-, -0(-0)РНЭ, -Ф(-О)М(Н)Нба, -С(-О)М( Nea)Be", -0(-0)0-H85, -M(Nba)Be, -MO", -M(H)C(-O)He, -M(Nbe)C(-O) No, -МН)С(-О)М(На)Нев, -М(Нес)С(-О)М(Аба)Нев, -М(Н)С(-О0)ОНе, -М(Не)С(- 0)ОНе, -М(Н)Б(-О)Не, -М(Нбе)5(-О0)Н5Я, -М(Н)Б(-0)286, -М(Нбс)5(-0) 286, -М-5(-0)(Нба)Нбб, -ОНб, 0 -О(0-О)Не, -О(С-О)М(Нба)не» -О(0-0)0Нб, -585, -5(-0)Н5, - 5(-О)М(Н)НЯ, -5(-0)М(Нба)Нев, -5(-0)2Н56, -5(-0)2М (H) He, -55-0)2M(Nea)BAe" or -5(-0(-M Ag) He; where the indicated C-C-Alkoxy-, aryl-, 3-7--ene heterocycloalkyl- or heteroaryl is optionally substituted, identically or differently, 1, 2 or C C.: -Cv-alkyl, Ci-Ci-alkyl-, halo-C1-Ci-Alkoxy-, -C(-0)0-AE or -OH groups.

In another preferred embodiment, the invention relates to a compound of formula I, above, wherein:

B' means hydrogen or a halogen atom or HO-, -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl, HO-C.1-Cv-alkyl, aryl-, heteroaryl- , -С(-О)М(Неа)Ве, "-"Ж(Н)С(-О)Не, -Ш(Н)С(-О)М(Веа)Ве", - оо, -55- 0)NO or -5(-0)2Н85; where the indicated C:1-C8- alkoxy- or heteroaryl is optionally substituted, identically or differently, by C1-C4-alkyl-, halo-C1-C8- alkoxy-, -C(-O)0-H5 or - ON; or when 2 КК" groups are in the ortho position to each other on an aryl or heteroaryl ring, the indicated 2 КЕ" groups together form a bridge: "О(СнггЬО" "СОСНУ" "МН(С(-О))МН", where " means the site of attachment to the indicated aryl or heteroaryl ring.

In another preferred embodiment, the invention relates to a compound of formula I, above, wherein:

B' means hydrogen or a halogen atom or HO-, -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl, HO-C:-Cv-alkyl, aryl-, heteroaryl-, -С(-ОМ(Ва)Ве», -Ш(Н)С(-О)Не, -«Ш(Н)С(-ОМ(ВЯВЬ, -

Shshch OH, -5(-0)NE or -5(-0)2186; where the indicated C:1-C8- alkoxy- or heteroaryl is optionally substituted, identically or differently, by C1-C4-alkyl-, halo-C1-C8- alkoxy-, -C(-O)0-HE or - ON.

In another preferred embodiment, the invention relates to a compound of formula I, above, wherein:

B" means hydrogen or a halogen atom or HO-, -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl, HO-C.1-Cv-alkyl, aryl-, heteroaryl- , -С(-О)М(Неа)Ве, "-"Ж(Н)С(-О)Не, -Ш(Н)С(-О)М(Веа)Ве", -

Onwe, -5(-0)НЕ or -5(-0)2НЕ; where the specified heteroaryl is optionally substituted C1-C4-alkyl; or when 2 B" groups are in the ortho position to each other on an aryl or heteroaryl ring, the specified 2 КЕ" groups together form a bridge: "О(СнггЬО" "СОСНУ" "МН(С(-О))МН", where " means the site of attachment to the indicated aryl or heteroaryl ring.

In another preferred embodiment, the invention relates to a compound of formula Y, where

B' means a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl,

HO-C.-Cv-alkyl, H2M-C1-Cv-alkyl, Co-Cv-alkenyl, 3-7-ene heterocycloalkyl, -C(-O)M(H)Vea, -M(Vba)Bev, -ЖН)С(-О) NE or -585; where the indicated Ci-Cv- alkoxy- or 3-7-ene heterocycloalkyl- is optionally substituted, identically or differently, by 1, 2 or C Ci-Cv-alkyl, Ci-Cv-alkyl-, halo-C1- S-Alkoxy-, -C(-0)0-86 or -OH groups.

In another preferred embodiment, the invention relates to a compound of the formula I, where KE" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, C:i-Cv-alkyl, halo-Ci-Cv-alkyl . Alkoxy-C1-Cv-alkyl, C-Cv-alkenyl, 3-7--ene heterocycloalkyl, aryl-, heteroaryl-, -C(-0)HE, -F(-OM(H)BYAa, -C(- О)М(ВЗа)Ве, -С(-0)0-86, -М(Нба)Ве», -МО», -М(Н)С(-О)Н8е, -М(Нег)С(- О) Ve, -МН)С(-О)М(На)Nev, -М(Нес)С(-О)М(Аба)Неv, -М(Н)С(-О0)ОНе, -М(Не )С(-0)ОНе, -М(Н)Б(-О)Не, -М(Нбс)5(-0)Н5, -М(Н)Б(-0)285, -М(Нес)Б (-0)2Нб, -М-5(-О)(Нба)НЕВ -0Нб 0 -О(0-0)Н, -О(С0-О)М(Нба)Не», -0(0-0 )ОН5, -5АЕ, -5(-0)Н8, - 5(-О)М(Н)Не, -5(-0О)М(Нба)Бей, -5(-0)2Н6, - 5(- 0)2M(H)He, -5(-0)2M(Nea)Be" or -5(-0)(-M Abe)Be; where Ci-Cv-alukoxy-, aryl-, C3-7- is indicated -ene heterocycloalkyl or heteroaryl is optionally substituted, identically or differently, 1Ci-Ci-alkyl, Ci-Ci-Alkoxy-, halo-C1-Ci-Alkoxy-, -C(-0)0-H5 or - ON groups.

In another preferred embodiment, the invention relates to a compound of formula I, where K" means hydrogen or a halogen atom, or HO-, -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl, HO -WITH-

Cn-alkyl, H2M-Ci-Cn-alkyl, C2-Cn-alkenyl, 3-7-membered heterocycloalkyl, -C(-O)M(H)Bea, -M(Bba)Be, -Ш(Н)С (-О)В? or -585; where the specified C1-C1-alkoxy- or 3-7-ene heterocycloalkyl- is optionally substituted, identically or differently, by one -C(-0)0-HE or -"OH group.

In another preferred embodiment, the invention relates to a compound of formula Y, above, where the 2 K" groups are in the ortho position to each other on the aryl or heteroaryl ring of the KZ group; the indicated 2 K" groups together form a bridge: "O(CHggo", " О(СНаО), ""Сна«СНаМНУ, "снения, "МН(С(-О)МНУ, "Ф(Н)-Ф(Н)-Ф(-0)-МЩ(НУ), where 7" means the place attachment to the specified aryl or heteroaryl ring.

Preferably, 2 K" groups together form a bridge selected from: "bnaSNgzagmn"U, "SngsNnMm(Be)SNe", "C(H)-C(H)-C(-0)-M(H)".

The invention relates to the compound of formula I, above, where

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl,

Vba(de)M-Si-Cv-alkyl, HO-C:-Cv-alkyl, Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, C2-Cv -alkenyl-, C3-7/--ene heterocycloalkyl, aryl-, heteroaryl-, -0(-0)РНЭ, -Ф(-О)М(Н)Нба, -С(-О)М(Неа)Бе », -0(-0)0-Н85, -М(Нба)Ве, -МО», -М(Н)С(-О)Не, -М(Нбе)С(-О)Не, -МН) С(-О)М(На)Нев, -М(Нес)С(-О)М(Аба)Нев, -М(Н)С(-О0)ОНе, -М(Не)С(-0)ОНе , -M(H)B(-O)He, -M(Nbs)5(-0)H5, -M(H)B(-0)285, -M(Nes)B(-0)2Nb, - М-5(-О)(Нба)НЯВ -0Нб 0 -О(0-0)Н, -О(С-О)М(Неа)ВЯ» -О(0-0)0ОН?, -586, - 5(-0)Н88, -5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, 0 -5(-0)2М(Н) Be, -5(-0)2M(Vba)Be», -55--0)(-MAVAE or -5(-0)2-(3-7-membered heterocycloalkyl); where 3-7-membered heterocycloalkyl is indicated - or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyls.

In a preferred embodiment, the invention relates to a compound of formula I, above, wherein:

ВЯ means a halogen atom, or -CM, -OH, C:-Cv-Alkoxy-, C-Cv-Alkyl, HO-C:-Cv-Alkyl, (-5(-0)M(Вba)рВеї, -М (Нба)Не»х, -М(Н)С(-О)Н, -М(Нес)С(-О)М(ВАба)Бей, -5(-0)2859 or -(-0)2OH .

In another preferred embodiment, the invention relates to a compound of formula I, above, wherein:

ВВ means a halogen atom, and -СМ, -М(Неа)Бе» or -ОВ2 dgoyr.

Preferably, KE means a halogen atom, a-Mm(Nea)Be" or -ONB: adgoyr.

The invention relates to a compound of formula I, where 10) t means an integer 0, 1, 2, 3, 4, 5 or 6.

In the preferred embodiment, in the compound of formula I, above, t is 0.

In another preferred embodiment, in the compound of formula I, above, t is equal to 1.

The invention relates to a compound of formula I, where n is an integer 0, 1, 2, 3, 4 or 5.

In the preferred embodiment, in the compound of formula I, above, n is equal to 1.

The invention relates to a compound of formula I, where

X is 5, 5(50), 5(50)2, O, MA, SHINE" or C-Svvarde,

In a preferred embodiment, the invention relates to a compound of formula Y, where

Hev.

In another preferred embodiment, the invention relates to a compound of formula I, where

X is 5(0).

In another preferred embodiment, the invention relates to a compound of formula Y, where

X is 5(0)".

In another preferred embodiment, the invention relates to a compound of formula Y, where

Ho.

In another preferred embodiment, the invention relates to a compound of formula I, where

X is MEE. X is preferably MH or M(CH33). Most preferably, X is MN.

It should be noted that in the group, for example, the formula aryl-MAE- or heteroaryl-MAE- the substituent

AND? may be optionally attached to an aryl or heteroaryl ring, thus - together with the M atom - forming a heterocyclic ring fused to an aryl or heteroaryl ring. An example of such a condensed ring system is the group:

WITH

, where 7" means the point of attachment of the specified group to the molecule. In other words, the group of the formula

WITH

, where 7" means the point of attachment of the specified group to the molecule, is an example of an aryl-X group.

In another preferred embodiment, the invention relates to a compound of formula Y, where

X is CEare", Preferably X is SN".

It should be noted that in the group, for example, of the formula aryl-Snvade»- or heteroaryl-CHbare-, the substituents ba and/or Psb5 may be optionally attached to the aryl- or heteroaryl ring, thus forming one or more carbocyclic rings fused to aryl or heteroaryl ring. An example of such a condensed ring system is the group , where 7" means the point of attachment of the indicated group to the molecule. In other words, the group of the formula , where " means the point of attachment of the indicated group to the molecule, is an example of an aryl-X group.

In another preferred embodiment, the invention relates to a compound of formula Y, where

X is C-Svvardb, Preferably X is C-CH."

The invention relates to a compound of formula I, where 2 means -C(-O)M(H)A: or -C(-55M(H)B: or a group selected from

ZE t3bU M ruch rudder

Hn Hn MN M and M Ya

MI MI-- MI-- 2 2 2 2 2 M M

A V A N i N j ; V Y ; - - MN M of Mr. Nyshe v

M 2 2 x ! - M 2

Н в в -М и в де" indicates the place of attachment of the indicated groups to the molecules.

In a preferred embodiment, 7 means -C(-O)M(H)B.

In another preferred embodiment, 2 means -C(-5)M(H)B-.

In another preferred embodiment, 2 means what

MN

What in?

In an embodiment of the above aspects, the invention relates to a compound of formula Y, according to any of the above embodiments, in the form of its stereoisomer, tautomer, M-oxide, hydrate, solvate, or its salt, or a mixture thereof.

It should be understood that the present invention also applies to any combination of the preferred embodiments described above.

Some examples of combinations are given in this document below. However, the invention is not limited to these combinations.

In a preferred embodiment, the invention relates to a compound of the general formula Y, above, where:

A means 4a in 4r. in yes in 7 4c in where " indicates the place of attachment of the specified groups to the molecule; 2 means -С(-О)М(Н)В2 or -С(-5)М(Н)В, or a group selected from xpt- 8Й8- t- tk

He GO ke Y MN nt thu - shk shk ey ey y ZhK y V ZhK r y 2 2 2 M M

A V A N i N

A. tov her I Ko MN mn sho shi she a zh

M 2 2 and ! - m 2

N v v -- M . where " indicates the place of attachment of the indicated groups to the molecule;

IN? means a hydrogen atom, or C.i-Cv-alkyl, halo-C1-Cv-alkyl, Nea(Bev)M-C-Cv-alkyl, HO-C1-Cv-alkyl, -C1-Cv-alkyl-CM, C1-Cv-Alkoxy-C1-Cv-Alkyl, Halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, C1-Cv-Alkenyl-; C2-C6-alkynyl- or C3-C6-cycloalkyl-; where the indicated C3-Cv-cycloalkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 groups selected from the following: halogen, OH, -CM, Ci-Cv-alkyl, -C1-Cv -Alkoxy, halo-C1-

St-alkyl;

BZ means a hydrogen atom or a halogen atom, or -CM, Ci-Cv-alkyl, -CHNg)t-C2-Cv-alkenyl, - (CHg)t-Ca-Cv-cycloalkenyl. -(CHn)t-C2-C6-alkynyl, -(CHn)t-C3-Ce-cycloalkyl, -(CHn)t-(3-7-ene heterocycloalkyl), -(CHn)t-(4- 8-ene heterocycloalkenyl), aryl-C1-C6-alkyl, heteroaryl-C-

C 1 -alkyl, halo-C 1 -C 2 -alkyl, Bba(BeB)M-C 1 -C 2 -alkyl, halo-C 1 -C 2 -alkyl-C 1 -C 2 -alkyl, /C 3 -C 2 -cycloalkyl, 3-7-- linoleic heterocycloalkyl, Co-Cv-alkenyl-, C.-Cv-cycloalkenyl-, Co-Cv-alkynyl-, aryl-, -C1-Cv-alkyl-aryl, -C1-Cv-alkyl-heteroaryl, heteroaryl-, C :i-Cv-alkyl-X-, -X-(CHg)t-C2-Cv-alkenyl, -X-(CHg)t-Ca-Cv-cycloalkenyl,. -X-(CHg)t-C2-Cv-alkynyl, -X-(CHeg)t-C3-Cv-cycloalkyl, -X- (CHg)t-(3-7-membered heterocycloalkyl), -X- (СНег)т-(4-8-membered heterocycloalkenyl), aryl-х-, heteroaryl-х-, -С(-0)НЭ, -С(-0О)М(Н)АТа, -С(- O)M(Vba)Ve, -0(-0)0-H85, -M(Nbg)VYA, -MO", -

M(H)C(-O)H8e, -OH88, -51885,. -5(-0)Н5, -55-0)285, -5(-0)(-МНба)Ве, -5(-0)2М(Н)Нес, -5-(СНе) n-

M(Bba)re" or -5-(CHn)n-(3-7-membered heterocycloalkyl); where indicated C:-Cv-alkyl, -(CHg)t-C2-Cv-alkenyl, -(CHg)t-C2-Cv-alkynyl, -(CHg)t-C3-Cv- cycloalkyl, aryl-Ci-Cv -alkyl, heteroaryl-Ci-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, Cc-Cv-alkenyl-, C«-Cv-cycloalkenyl-, C2-Cv-alkynyl-, aryl-, C1 -C1-alkyl-X-, -X- (CHn)t-C2-Cn-alkenyl, -X-(CHn)t-Ca-Cn-cycloalkenyl, -X-(CHn)t-C2-Cn-alkynyl, -X-(CHg)t-C3-Cv- cycloalkyl, -X-(CHg)t-(3-7-membered heterocycloalkyl), -X-(CHg)t-(4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-x-, -C1-C1-alkyl-aryl, -C1i-C1-alkyl-heteroaryl or heteroaryl is optionally substituted, identically or differently, with 1, 2, C or 4 B" groups ; da, DV, des, DYA mean, independently of each other, hydrogen or a halogen atom, or -CM,

C-Cv-alkyl, C-Cv-alkoxy-, halo-Ci-Cv-alkyl, Kea(Bev)M-C1-Cv-alkyl, 8 HO-C1-Cv-alkyl, C1-Cv-

30 /Alkoxy-C1-Cv-alkyl, halo-C1-Cv-Alkoxy-C1-Cv-alkyl, -C(-O)HE, -C(-O)M(H)Aea, -C(-O) М(Неа)де», -б(-0)0-НЕ, -М(Бе)ВЕ», -МО», -М(Н)С(-О)НЕ, 0 -М(Бе)С(- 0)8E, 0 -Ш(Н)С(-О)М(ВегВе», -М(Вег)С(-О)М(Веа)Веј, -М(Н)С(-0О)ОНе, -М (Be)C(-0)086, -M(H)B(-O)BE, 0 -M(Be8(-O)8e, -M(H)B(-0)285, -M(Nbg) 5(-0)286, -М-5(-0О)(Нба)Вбё, -ОНЯ, -О(С0-0)Н5, -О(С-О)М(Нбг) Бе, -б(0- Ф0)0НЕ, -5Ве, -5(-0)86, -5(-0)М(Н)ВЕ, -5(-О)М(Вг)ВЕ, -5(-0)286, -5( -0)2M(H)Ve», -5(-0)2M(Vea)De» or -5(-0)(-MAes) Ve.

IN? means a hydrogen atom or C1-Cv-alkyl, -(CHg)n-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -( SnHg)t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Beb)M-C1-Cv-alkyl, HO -C:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, CgO-Cv-alkenyl-, C4-Cv- cycloalkenyl-, C1-C8-alkynyl-, aryl- or heteroaryl; where Ci-Cv-alkyl, -(CHg)n-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-membered heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-C1-Cv-alkyl, halo-Ci-Cv-alkyl, Kba(Neu)M-C1-Cv-alkyl,, HO-C1- C1-alkyl, -C1-Cv-alkyl-СМ, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-Ci-Cv-Alkoxy-C1-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, Ca4-Cv- cycloalkenyl-, aryl- or heteroaryl- is optionally substituted, identically or differently, by 1, 2, C or 4 P8 groups;

Ve, ba, DOV, res mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C1-

C1-alkyl, C3-C8-cycloalkyl, Co-C8-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C8-alkyl- or heteroaryl-C:-C8-alkyl-;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Nea(Bev)M-Ci-Cv-alkyl, HO- S.: -Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-О)НЕ, -ФШ(-ОМ(Н)АЯа, -С(-О)М( Vta)Ve, -C(-0)0-86, -M(Vba)Ve", -MO", -M(H)C(-O)H8e, -M(Neg)C(-O)8e, -МН)С(-О)М(На)Ве, "(Не С(-О)М(Ата)Ве, -М(Н)С(-О)ОВе, -М(Не)С(-ООНВе, -МЩ(Н)(-ОНе, -М(Нбс)5(-0)Н5, -М(Н)Б(-0)285, -М(Нес)Б(-0)2Нб, -М-5( -О)(Нба)НЯВ -0Нб 0 -О(0-0)Н, -О(С-О)М(Нба)не» -О(0-0)0Нб, -585, -5(-0) Н5, - 5(-О)М(Н)НЯ, -5(-0)М(Нба)Нев, -5(-0)2Н56, -(-0)2М(Н)Не, -55-0) 2M(Nea)Be, -5(-0(-M es) He; where the indicated aryl or heteroaryl is optionally substituted, identically or differently, with 1, 2 or C C-Cv alkyls; or when 2 K" groups are in the ortho position to each other on the aryl ring, 2 are indicated

B' groups together form a bridge: "О(Снг)гБО" "О(СНУБО" "МН(С(-О))МН", where " means the place of attachment to the indicated aryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, vea(He)M-C1-Cv-Alkyl, HO-C.i-Cv -alkyl, C1-Cv-Alkoxy-Ci-Cv-alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, Co-Cv-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, - 0(-0)РНЕ, -Ф(-О)М(Н)Нба, -С(-О)М(Неа)Бе», -0(-0)0-Н85, -М(Нба)Бе, - MO", -M(Н)С(-О)Не, -М(Нбе)С(-О)Не, -МН)С(-О)М(На)Nev, -М(Нес)С(-О) )М(Аба)Нев, -М(Н)С(-О0)ОНе, -М(Не)С(-0)ОНе, -М(Н)Б(-О)Не, -М(Нбс)5( -0)Н5, -М(Н)Б(-0)285, -М(Нес)Б(-0)2Нб, -М-5(-О)(Нба)НЯВ -0Нб 0 -О(0-0 )Н, -О(С-О)М(Нба)неЯ» -О(С0-0)ОНе, -52я58, -5(-0)Н5, -5(-0)М(Н)Н5, -5 (-0)M(Nba)Ve, -5(-0)2H56, -(-0)2M(H)NVe, -5(-0)2M(a)Ve, -5(-0(-МА82) ВЭ or - 5(-0)2-(3-7-membered heterocycloalkyl); where the indicated 3-7-membered heterocycloalkyl- or heteroaryl is optionally substituted, identically or differently, 1, 2, C or 4 Ci-Cv-alkyl; t is an integer 0, 1, 2, 3, 4, 5 or 6; n is an integer 0, 1, 2, 3, 4 or 5;

X is 5, 5(50), 5(5О)»2, О, HAS; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

In another preferred embodiment, the invention relates to a compound of the general formula |, above, where:

A means vy, Vie vie 7 does where "indicates the place of attachment of the indicated groups to the molecule; 2 means -С(-О)М(Н)А: or -С(-5)М( H) B, or a group selected from yat-8y-t-6-to

Hn on Kn MU cm MU cm

MI sho sho ey u u same ZhK y V ZhK y y 2 2 2 M M

In A N I N

A. tov her I Ko MN mn sho shi she a zh

M 2 2 " ! -M 2

N v v -- M . where " indicates the place of attachment of the indicated groups to the molecule;

IN? means a hydrogen atom, or C.i-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bev)M-C-Cv-alkyl, HO-C1-Cv-alkyl, -C1-Cv-alkyl-CM, C1-Cv-Alkoxy-C1-Cv-Alkyl, Halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, C1-Cv-Alkenyl-; C2-C6-alkynyl- or C3-C6-cycloalkyl-; where the indicated C3-Cv-cycloalkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 - groups selected from: halogen, OH, -CM, C1-Cv-alkyl, -C1-Cv- alkoxy, halo-C1-C1-alkyl;

BZ means a hydrogen atom or a halogen atom, or -CM, C1-Cv-alkyl, -(CHn)t-C2-Cv-alkenyl-, 10. -(CHneo)t-C4-Cv-cycloalkenyl, -(CHe) t-C2-Cv-alkynyl, -(CH2g)t-C3-Cv-cycloalkyl, -(CHe)t-(3-7-membered heterocycloalkyl), -(CNeg)t-(4-8-membered- linoleic heterocycloalkenyl), aryl-C1-Cv-alkyl, heteroaryl-C:-Cv-alkyl, halo-C1-Cv-alkyl, Kba(Beu)M-C1-Cv-alkyl, halo-C1-Cv-alkyl-C1 -Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cv-alkenyl-, Ca-Cv-cycloalkenyl-, C2-

C1-C8-alkynyl-, aryl-, -C1-C8-alkyl-aryl, -C1-C8-alkyl-heteroaryl, heteroaryl-, C1-C8-alkyl-xX-, 15. -X-(CNeo)t-C2- Св-alkenyl, -Х-(СНег)т-Са-Св-cycloalkenyl,. -X-(CHg)t-C2-Cv-alkynyl, -X-(CHg)t-C3-Cv-cycloalkyl, -X-(CHg)t-(3-7-membered heterocycloalkyl), -X- (CHg)t-(4-8-membered heterocycloalkenyl), aryl-Xx-, heteroaryl-Xx-, -C(-0)H8E, -C(-O)M(H)NYA, /-C(-O )М(Веа)Ве», -(-03)0-Не, -М(Вба)Ве», -МО», -Ш(Н)С(-О0)Не, -Оов8е, -5185, -5( -0O)He, -5(-0)2H85, -5(-0(-M Aa), -5(-0)2M(HeB) Ves, -5-(CHg)p-M(Hba) Be» or -5-(CHn)n-(3-7-membered heterocycloalkyl); where C:-Cn-alkyl, -(CHn)t-C2-Cn-alkenyl, -(CHn)t-C2-Cn-alkynyl is indicated . -Cv-cycloalkenyl-, C2-Cv-alkynyl-, aryl-, C-Cv-alkyl-X-, -X-(CHg)t-C2-Cv-alkenyl, -X-(CHg)t-Ca-Cv -cycloalkenyl, -X-(CHg)t-C2-Cv-alkynyl, -X-(CHg)t-C3-Cv-cycloalkyl, -X-(CHg)t-(3-7-membered heterocycloalkyl), -X-(CHg)t-(4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-x-, -C1-C6-alkyl-aryl, -C1-C6-alkyl-heteroaryl or heteroaryl is optional substituted, identically or differently, 1, 2, Z or 4 V" groups; or

Vl, De, ДЯ mean a hydrogen atom, and

A" means a hydrogen atom or a halogen atom or C.1-Cv-alkyl-; or

В, Дие, ДЯ mean a hydrogen atom, and

Da means a halogen atom or C-Cv-alkyl, -ОНеЭ, -0(0-0О)Не, -0(С-О)М(Нег)Бе», -0(С0-О)ОНе, -586, - 5(-0)8e, -5(-OM(H) Be, -(-O)M(Veg)Be", -5(-0)28, -5(-0)2M(H) Be", -5(-0)2M(Be2)Be" or -(-0-MAeg)re;

B" means a hydrogen atom, or Ci-Cv-alkyl, -""CHn)p-C2-Cv-alkenyl, -"CHn)p-C2-Cv-alkynyl, -"CHe)t-

C3-Cv-cycloalkyl, -(CHg)t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-C1-Cv-alkyl, halo-C1-Cv-alkyl, Kba(Be») M-C1-Cv-alkyl, HO-C:-Cv-alkyl, -C1-Cv-alkyl-CM, Ci-Cv-Alkoxy-C1-

C1-alkyl, halo-C1-C1-alkoxy-C1-C1-alkyl, C3-C8-cycloalkyl, 3-7-membered heterocycloalkyl, Cg-

C-alkenyl-, C--Cv-cycloalkenyl-, Cg-Cv-alkynyl-, aryl- or heteroaryl; where Ci-Cv-alkyl, -(CHg)n-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-membered heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-C1-Cv-alkyl, halo-Ci-Cv-alkyl, Kba(Neu)M-C1-Cv-alkyl,, HO-C1- C1-alkyl, -C1-Cv-alkyl-СМ, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-Ci-Cv-Alkoxy-C1-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, Са4-Св- cycloalkenyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2,

With or 4 E8 groups;

Ve, Vba, dDBB, Des mean, independently of each other, a hydrogen atom, or Ci-Cv-alkyl, HO-C-

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bea(Bev)M-Ci-Cv-alkyl, HO- S.: -Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, C2-C1-alkenyl, C-7/-membered heterocycloalkyl, aryl-, heteroaryl-, -С(-0)НЕ6, - c(-О)М(Н)веа, -С(- О)М(Веа)Ве, -2(-0)0-Н8Е, -М(Вба)Ве», -МО», -Ш(Н)С(-О)Ве, -М(В85)0(- O)H8, -

M(H)C(-O)M(Neg)BAeB, -M(He)C(-O)M(Bea)Be, -(H)C(-OONe, -M(He)C(-0) ОН8е, -М(Н)(-О)Ве, -

М(Нбс)5(-О0)НЯ, -М(Н)Б(-0)286, -М(Нег)В(-0)2Нб, -М-5(-О)(Нба)ВЯ", - НЕ, -О(0-0)НЕ, (-

О(С-О)М(Неа)Бе», -0(0-0)ОН6, -586, -5(-0)Н8, - 5(-О)М(Н)Н, -5(-0О )M(Nba)Be, -5(-0)2H5, - 5(-0)2M(H)He, -5(-0)2M(Nea)Be" or -5(-0)(-M Abe ) Ve; where the indicated aryl- or heteroaryl is optionally substituted, identically or differently, by 1, 2 or C C-Cv alkyls; or when 2 K" groups are ortho to each other on the aryl ring, 2 are indicated

B' groups together form a bridge: "О(СнггБ5О", "О(СНУО), "МН(С(-О))МНУ, where " means the place of attachment to the specified aryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, vea(He)M-C1-Cv-Alkyl, HO-C.i-Cv -alkyl, C1-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, C2-Cv-Alkenyl-, C3-7/--ene heterocycloalkyl, aryl-, heteroaryl- . , -MO», -M(Н)С(-О)Не, -М(Нбе)С(-О)Не, -МН)С(-О)М(На)Нев, -М(Нес)С( -O)M(Aba)Nev, -M(H)C(-0)OHe, -M(He)C(-0)OHe, -M(H)B(-O)He, -M(Nbs) 5(-0)Н5, -М(Н)Б(-0)285, -М(Нес)Б(-0)2Нб, -М-5(-О)(Нба)НЯВ -0Нб 0 -О(0 -0)Н, -О(С-О)М(Нба)неЯ» -О(С0-0)ОНе, -52я58, -5(-0)Н5, -5(-0)М(Н)Н5, -5(-0)M(Nba)Ve, -5(-0)2Н56, -(-0)2МЩ(Н)He, -55-0)2M(a)Ve, -5(-0)(- MA) or -5(-0)2-(3-7-membered heterocycloalkyl); where the specified 3-7-membered heterocycloalkyl or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyls; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5;

X is 5, 5(50), 5(20)2, O, MH; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

In another preferred embodiment, the invention relates to a compound of the general formula |, above, where:

A means vy, Vie vie 7 does where "indicates the place of attachment of the indicated groups to the molecule; 2 means -С(-О)М(Н)А: or -С(-5)М( H) B, or a group selected from yat-8y-t-6-to

Hn on Kn MU cm MU cm

MI sho sho ey u u same ZhK y V ZhK y y 2 2 2 M M

In A N I N

A. comrade her I Co. MN pln

As bod fr

M 2 2 " ! -M 2

Н в в -М х в де" indicates the place of attachment of the specified groups to the molecule;

IN? means a hydrogen atom, or C.i-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bev)M-C-Cv-alkyl, HO-C1-Cv-alkyl, -C1-Cv-alkyl-CM, C1-Cv-Alkoxy-C1-Cv-Alkyl, Halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, C1-Cv-Alkenyl-; C2-C6-alkynyl- or C3-C6-cycloalkyl-; where the indicated C3-Cv-cycloalkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 - groups selected from: halogen, OH, -CM, C1-Cv-alkyl, -C1-Cv- alkoxy, halo-C1-C1-alkyl;

BZ means a hydrogen atom or a halogen atom, or -CM, Ci-Cv-alkyl, -"CNeg)t-C2-Cv-alkenyl, , - 10. (CHag)t-C4-Cv-cycloalkenyl -(CHg)t- C2-Cv-alkynyl, -«"«CHn)t-C3-Cv-cycloalkyl, -(CHn)t-(3-7-membered heterocycloalkyl), -(CHn)t-(4-8--ene heterocycloalkenyl) , aryl-C1-C1-alkyl, heteroaryl-C-

C 1 -alkyl, halo-C 1 -C 2 -alkyl, Bba(BeB)M-C 1 -C 2 -alkyl, halo-C 1 -C 2 -alkyl-C 1 -C 2 -alkyl, /C 3 -C 2 -cycloalkyl, 3-7-- linoleic heterocycloalkyl, C2o-Cv-alkenyl-, C.-Cv-cycloalkenyl-, Co-Cv-alkynyl-, aryl-, -C1-Cv-alkyl-aryl, -C1-Cv-alkyl-heteroaryl, heteroaryl-, C1 -Cv-alkyl-X-, -X-(CHg)t-C2-Cv-alkenyl, -X-(CHg)t-Ca-Cv-cycloalkenyl, -X-(CHg)t-C2-Cv-alkynyl, -X-(CHn)t-C3-Cv-cycloalkyl, -X-(CHn)t-(3-7-membered heterocycloalkyl), -X-(CHeng)t-(4-8-membered heterocycloalkenyl ), aryl-x-, heteroaryl-x-, -С(-0)НЭ, -С(-О)3МЩ(Н)Нба, -С(-О)М(Нба)Нев, -0(-0) 0-H85, -M(Nba)Be", -MO", -

М(Н)С(-О0)Не, -ОН88, -5186,. -5(-0)H86, -5(-0)285,. -5(-0(-MHba)Nev, -5(-0)2M(Hb)Aes, -5-(CHg)p-

M(Bba)Be" or -5-(CHn)p-(3-7-ene heterocycloalkyl); where indicated C:-Cv-alkyl, -(CHg)t-C2-Cv-alkenyl, -(CHg)t-C2-Cv-alkynyl, -(CHg)t-C3-Cv- cycloalkyl, aryl-Ci-Cv -alkyl, heteroaryl-Ci-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, Cc-Cv-alkenyl-, C«-Cv-cycloalkenyl-, C2-Cv-alkynyl-, aryl-, C1 -C1-alkyl-X-, -X- (CHn)t-C2-Cn-alkenyl, -X-(CHn)t-Ca-Cn-cycloalkenyl, -X-(CHn)t-C2-Cn-alkynyl, -X-(CHg)t-C3-Cv- cycloalkyl, -X-(CHg)t-(3-7-membered heterocycloalkyl), -X-(CHg)t-(4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-x-, -C1-C1-alkyl-aryl, -C1i-C1-alkyl-heteroaryl or heteroaryl is optionally substituted, identically or differently, with 1, 2, C or 4 B" groups or

Vl, De, ДЯ mean a hydrogen atom, and

A" means a hydrogen atom or a halogen atom or C.1-Cv-alkyl; or

В, Дие, ДЯ mean a hydrogen atom, and

Da means a halogen atom or C-Cv-alkyl, -ОНеЕ, -0(0-0О)Не, -0(С-О)М(Нег)Бе», -0(С0-О)ОНе, -5Не, - 5(-0)H8, -(-OM(H)He, -5(-0O)M(Aba)Be, -5(-0)286, -5(-0)2M(H)Be, -5 (-0)2М(НАг)Бе» or -(-0у-МА) Ne;

B" means a hydrogen atom, or Ci-Cv-alkyl, -(CHg)t-(3-7-membered heterocycloalkyl), aryl- or heteroaryl; where the specified Ci-Cv-alkyl, -(CHg)t-(3-7--lene heterocycloalkyl), aryl- or heteroaryl is optionally substituted, identically or differently, by 1, 2, 3 or 4 KZ groups;

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C--

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kea(Nev)M-C1-Cv-alkyl, HO- C:1-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, C1-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-0О)НЭ, -Б(-ОМ(Н)БЯа, -С(-О)М( Vba)Ve, -С(-0)0-86, -M(Nba)Ve», -MO», -M(Н)С(-О)НЕ, -M(Вбг)С(-О) Ve, -МН)С(-О)М(На)Ве, "(Не С(-О)М(Ата)Ве, -М(Н)С(-О)ОВе, -М(Не)С(-ООНВе, -МЩ(Н)(-ОНе, -М(Нбг)5(-0)Н8АУ, -М(Н)Б(-О0)28?, -М(Нбе)Б(-0)2Н5, М-5( -О)(Н)Ай -ОВ8б, 0 -О(С0-О)88,

-O(С-О)М(Нба)не» -0(0-0)ОН5, -586, -5(-0)Н8, -5(-О)М(Н)Н, -5(-0О )M(Nba)Be», -5(-0)286, - 5(-0)2M(H)He, -5(-0)2M(Наеа)Be, -5(-0)(-М Abe ) Ve; where the specified aryl-, heteroaryl- is optionally substituted, identically or differently, by m/y 1, 2 or C C -Cv alkyls; or when 2 BE" groups are ortho to each other on the aryl ring, 2 are indicated

B' groups together form a bridge: "О(СнггБ5О), "(НОО "МН(С(-О))МНУ, where " mean the place of attachment to the specified aryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl,

Vba(Bev) M-Ci-Cv-alkyl, HO-Ci-Cv-alkyl, Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, Co-Cv- alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -0(-0)РНЕ, -Ф(-О)М(Н)Нба, -С(-О)М(Неа)Бе», - 0(-0)0-Н85, -М(Нба)Ве, -МО», -М(Н)С(-О)Не, -М(Нбе)С(-О)Не, -МН)С(- О)М(На)Нев, -М(Нес)С(-О)М(Аба)Нев, -М(Н)С(-О0)ОНе, -М(Не)С(-0)ОНе, -М (Н)Б(-О)Не, -М(Нбг)5(-0)Н8Я, -М(Н)Б(-О0)28?, -М(Нбг)5(-0)2НЯ, -М- 5(-О)(Н)ВА -ОВ8б, 0 -О(0-О)Б8е, -О(С-О)М(Неа)ВЯ» -О(0-0)0ОН?, -586, -5 (-0)Н88, -5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, -(-0)2МЩ(Н)Не, - 55-0)2M(Hg)Ve, -5(-0-MA), -5(-0)2-(3-7-membered heterocycloalkyl); where the specified 3-7-ene heterocycloalkyl- or heteroaryl- is optionally substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyl-; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5;

X is 5, 5(-50), 5(-0)2, O, MA; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

In another preferred embodiment, the invention relates to a compound of the general formula |, above, where:

A means yes

IN

4 years In yes

At 7 4 p.m

Where " indicates the place of attachment of the specified groups to the molecule; 2 means -C(-O)M(H)B2 or -C(-5)M(H)B, or a group selected from xpt»8- thu M- rulch rUl-« pn Hn MN M I M I

MI Mosch Mo 2 2 2 2 2 M M

В А Н х Н 0) ; ; ; , , ro i V Y i

MU tm lis li Y Mn sh- sh- MN M -- ЖК y o M M dn 4 I x-

M 2 2 " ! -k 2

Н В В -М я В where " indicates the place of attachment of the indicated groups to the molecule;

B means a hydrogen atom, or C.i-Cv-alkyl, halo-C1-Cv-alkyl, Bba(8bv)M-C-Cv-alkyl, HO-C1-Cv-alkyl, -C1-Cv-alkyl-CM . where the specified C3-Cv-cycloalkyl is optionally substituted, identically or differently, with 1, 2, C or 4 groups selected from: halogen, OH, -CM, C1-C8-alkyl, C1-C8-alkyl-, halo-C1-C1-alkyl-;

BZ means a hydrogen atom or a halogen atom, or -CM, C1-Cv-alkyl, -(CHg)t-C2-Cv-alkenyl, -(CHg)t-Ca-Cv-cycloalkenyl -(CHg)t-C2-Cv -alkynyl, -CHn)t-C3-Cv-cycloalkyl, -(CH2g)t-(3-7-membered heterocycloalkyl), -(CHn)t-(4-8-membered heterocycloalkenyl), aryl-C1- C-alkyl, heteroaryl-C-

C 1 -alkyl, halo-C 1 -C 2 -alkyl, Bba(BeB)M-C 1 -C 2 -alkyl, halo-C 1 -C 2 -alkyl-C 1 -C 2 -alkyl, /C 3 -C 2 -cycloalkyl, 3-7-- linoleic heterocycloalkyl, C2o-Cv-alkenyl-, C.-Cv-cycloalkenyl-, Co-Cv-alkynyl-, aryl-, -C1-Cv-alkyl-aryl, -C1-Cv-alkyl-heteroaryl, heteroaryl-, C1 -Cv-alkyl-X-, -X-(CHg)t-C2-Cv-alkenyl, /-X-(CHg)t-Ca-Cv-cycloalkenyl, -X-(CHg)t-C2-Cv-alkynyl , -X-(CHg)t-C3-Cv-cycloalkyl, -X-(CH2g)t-(3-7-membered heterocycloalkyl), -X-(CHg)t-(4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-x-, -С(-0)НЭ, -С(-0О)М(Н)Аба, -С(-О)М(Нба)Бе», -0(-0)0 -Н8, -М(Нба)Бе», -МО», -ЖХХНС(-0)Н, -0Н8б -58Н5, -5(-0)Нб, -5(-0)285, -5(-0) (-MAba)BeB, /-5(-0)2M(BbB)Abe, -5-(CHg)n-M(Beba)Be» or -5-(CH2g)p-(3-7-- linoleic heterocycloalkyl); where indicated C:-Cv-alkyl, -(CHg)t-C2-Cv-alkenyl, -(CHg)t-C2-Cv-alkynyl, -(CHg)t-C3-Cv- cycloalkyl, aryl-Ci-Cv -alkyl, heteroaryl-Ci-Ci-alkyl, C3-Ci-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Ci-alkenyl-, C4-Ci-cycloalkenyl-, C2-Ci-alkynyl-, aryl-, Ci- Cn-alkyl-X-, 15. -X-(CNeo)t-C2-Cn-alkenyl, -X-(CNeg)t-Ca-Cn-cycloalkenyl,. -X-(CHg)t-C2-Cv-alkynyl, -X-(CHg)t-C3-Cv-cycloalkyl, -X-(CHg)t-(3-7-membered heterocycloalkyl), -X- (CHn)t-(4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-x-, -C1-C6-alkyl-aryl, -C1-C6-alkyl-heteroaryl or heteroaryl is optionally substituted, identical or in different, 1, 2, C or 4 B" groups; or

Va, De, ДЯ mean a hydrogen atom, and

A" means a hydrogen atom or a halogen atom or C.1-Cv-alkyl; or

В, Дие, ДЯ mean a hydrogen atom, and

Da means a halogen atom or C-Cv-alkyl, -ОНеЭ, -0(0-0О)Не, -0(С-О)М(Нег)Бе», -0(С0-О)ОНе,

Yuts -586, -5(-0)Н8, -5(-0О)М(Н)Не, -6(-О)М(Вба)Ве, -5(-0)285, -5(-0) 2M(H) Na, -55-0)2M(Nea) Ve», -(-OC-MAeg)He;

B" means a hydrogen atom, or Ci-Cv-alkyl, -(CHg)t-(3-7-membered heterocycloalkyl), aryl- or heteroaryl; the indicated C1-C8-alkyl, -(CNeg)t-(3-7-ene heterocycloalkyl), aryl- or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 KZ groups;

Ve, Vba, dDBB, Des mean, independently of each other, a hydrogen atom, or Ci-Cv-alkyl, HO-C-

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kea(Nev)M-C1-Cv-alkyl, HO- C:1-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-0О)НЭ, -ФЩ(-ОМ(Н)АЯа, -С(-О)М( НЗа)Ве, -С(-0)0-86, -М(Вба)Ве», -МО», -М(Н)С(-О)Н8е, -М(Нег)С(-О)8е, -МН)С(-О)М(На)Ве, "(Не С(-О)М(Ата)Ве, -М(Н)С(-О)ОВе, -М(Не)С(-ООНВе, -МЩ(Н)(-ОНе, -М(Нб)5(-0)НЯ, -М(Н)Б(-О)285, -М(Нб)5(-0)285, -М-5( -О)(Н)ВАЙ -ОВ8б, 0 -О(0-О)8е, -О(С-О)М(Неа)ВЯ» -О(0-0)0ОН?, -586, -5(- 0)Н88, -5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, -(-0)2М(Н)НВе, -5( -0)2M(a)Ve, -(-0-M Ag); where the specified aryl- or heteroaryl is optionally substituted, identically or differently, by 1, 2 or C C-Cv-alkyls; or when 2 K "groups are present in the ortho position to each other on the aryl ring, the indicated 2 K" groups together form a bridge: "О(СнггЬО" "СОСНУ" "МН(С(-О))МН", where " means the place of attachment to the indicated aryl rings;

ВЗ means a halogen atom, -M(Neg)B?" or -ОВЕ; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5;

X is 5, 5(50), 5(-50)2, 0, HAS; or a stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

In another preferred embodiment, the invention relates to a compound of general formula I, above, wherein:

what's up, huh? takes 7 days

A means; where " indicates the place of attachment of the indicated groups to the molecule; 2 means -С(-О)М(Н)А: or -С(-5Х(Н) 2, or t

MN

M in? ; where " indicates the place of attachment of the indicated groups to the molecule;

IN? means a hydrogen atom, or Ci-Cv-alkyl- or C3-Cv-cycloalkyl;

BZ means a hydrogen atom or a halogen atom, or -(CHg)t-C2-Cv-alkenyl, -(CHg)t-Ca-Cv- cycloalkenyl -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (4-Y--lene heterocycloalkenyl), aryl-, aryl-X-, heteroaryl-X-, heteroaryl-, -C(-0O)3M(H)Aba, -08H65, -586,. -5I-O)H85, -5(-O)2H5, -5-(CHn)n-M(Veba)B" or -5-(CH2n)p-(3-7-ene heterocycloalkyl); where the indicated aryl-, aryl-X-, heteroaryl-X or heteroaryl is optionally substituted, identically or differently, with 1, 2, C or 4 K" groups; or

Va, De, ДЯ mean a hydrogen atom, and

AND?" means a hydrogen atom or a halogen atom or a Ci-Cv-alkyl; or

Ve, De, ДЯ mean a hydrogen atom, and

Where: means a halogen atom or Ci-Cv-alkyl- or -ONE;

B means C1-C6-alkyl, -(CH8)t-(3-7-membered heterocycloalkyl), aryl- or heteroaryl; the indicated C1-C8-alkyl, -(CNeg)t-(3-7-ene heterocycloalkyl), aryl- or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 RK groups;

Ve, Vba, dDBB, Des mean, independently of each other, a hydrogen atom, or Ci-Cv-alkyl, HO-C-

C 1 -alkyl, C 3 -C 6 -cycloalkyl- or aryl;

B" means hydrogen or a halogen atom or HO-, -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl, HO-C.1-Cv-alkyl, aryl-, heteroaryl- , -С(-О)М(Неа)Ве, "-"Ж(Н)С(-О)Не, -Ш(Н)С(-О)М(Веа)Ве", -

Onwe, -5(-0)НЕ or -5(-0)2НЕ; where the indicated heteroaryl is optionally substituted C1-C-alkyl; or when 2 B" groups are present in the ortho position to each other on the aryl ring, the specified 2 EC" groups together form a bridge: "О(СнгГО" "СОСНУ" "МН(С(-О))МН", where " means the position attachment to the specified aryl ring;

BB means a halogen atom, -М(Нба)Ве or -ОНВ; t means an integer 0, 1, 2, 3, 4, 5 or 6;

X is 5, 5(-0), 5(-0)2, O, HAS; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

In another preferred embodiment, the invention relates to a compound of the general formula |, above, where:

A means elm, willow, willow

N

4

Y v z M h o // M // M vya 7 vye vye or or d'z x -x vye - M 46

And NM

- ve or ; where " indicates the place of attachment of the indicated groups to the molecule; 2 means -C(-O)M(H)B2 or -C(-5)M(H)B, or a group selected from

ZE t3buOh M stream

Hn Hn MN M and M Ya

MI MI-- MI-- 2 2 2 2 2 M M

В В В Н х Н з з з з з ; V Y ; t МН 2 ш- ш--

Bl: no she she

M 2 2 x I -x 2

Н в в -М я А where 7" indicates the place of attachment of the indicated groups to the molecule:

IN? means a hydrogen atom, or C.i-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bev)M-C-Cv-alkyl, HO-C1-Cv-alkyl, -C1-Cv-alkyl-"CM . where the indicated C3-Cv-cycloalkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 - groups selected from: halogen, OH, -CM, C1-Cv-alkyl, -C1-Cv- alkoxy, halo-C1-C1-alkyl-;

BZ means a hydrogen atom or a halogen atom, or -CM, C1-Cv-alkyl, -C1-Cv-alkoxy, -(CHg)t-Seg-

Cn-alkenyl, -(CHn)t-C--Cn-cycloalkenyl /-(CHn)t-C2-Cn-alkynyl, -(CHn)t-C3-Cn-cycloalkyl, 15. -(CNe)t- (3-7-membered heterocycloalkyl), -(CHn)t-(4-8--ene heterocycloalkenyl), aryl-C1-Cv-alkyl, heteroaryl-C:-Cv-alkyl, halo-C1-Cv-alkyl, Bea(Bev»)M-C1-Cv-alkyl, halo-C1-Cv-Alkoxy-C1-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, Co-Cv-alkenyl-, Ca-Cv -cycloalkenyl-, C2-

C1-C8-alkynyl-, aryl-, -C1-C8-alkyl-aryl, -C1-C8-alkyl-heteroaryl, heteroaryl-, C1-C8-alkyl-xX-, -X-(CHg)t-C2-Cv- alkenyl, -X-(CHg)t-Ca-Cv-cycloalkenyl, -X-(CHg)t-C2-Cv-alkynyl, -X-(CHg)t-C3-Cv-cycloalkyl, -X-(CHg) t-(3-7-membered heterocycloalkyl), -X-(CHg)t-(4-8-membered heterocycloalkenyl), aryl-X-, heteroaryl-Xx-, -C(-0)H5, -0 (-0О)1М(Н)НЯ, -С(-О)М (Ва), --0)0-Не, -М(Вба)Ве», -МО», -Щ(Н)С(-О )Н8е, -ОНе, -5185, -5(-0)Н85, -5(-0)286, -5(--0)(-МНег) Ве», -(-0)2М(В)Вее, -5-(CHn)n-M(Bea)Be" or -5-(CHn)n-(3-7-membered heterocycloalkyl); specified C1-C8-alkyl, -C1-C8-alkyl, -(CHn)t-C2-C8-alkenyl, -«"CHen)t-C2-C8-alkynyl, -"CHen)t-C3-

Cn-cycloalkyl, aryl-C:i-Cn-alkyl, heteroaryl-Ci-Cn-alkyl, C3-Cn-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cn-alkenyl-, C4-Cn-cycloalkenyl-, C2 -Cv-alkynyl-, aryl-, Ci-Cv-alkyl-X-, -X-(CHg)t-C2-Cv-alkenyl, -X-(CHg)t-Ca-Cv-cycloalkenyl, -X-( CHg)t-C2-Cv-alkynyl, -X-(CHg)t-C3-Cv-cycloalkyl, -X-(CHg)t-(3-7-membered heterocycloalkyl), -X-(CHg)t -(4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-x-, -C1-C6-alkyl-aryl, -C1-C6-alkyl-heteroaryl or heteroaryl is optionally substituted, identically or differently, 1, 2, 3, 4 or 5 K" groups;

да, ДЬ, дъе, ДЯ mean, independently of each other, hydrogen or a halogen atom, or -СМ,

Ci-Cv-alkyl, Ci-Cv-Alkoxy-, halo-Ci-Cv-Alkyl, Kea(Bev)M-C1-Cv-Alkyl, 8 HO-C1-Cv-Alkyl, C1-Cv-Alkoxy-C1- C1-alkyl, halo-C1-C1-Alkoxy-C1-C1-alkyl, -C(-O)H, -C(-O)M(H)Nea, -C(-O)M (Na) Be» . (-О)М(Аг) Бе», -М(Нес)С(-О)М(Аба)вНе», -М(Н)С(-ОВЯ, 0 -М(Вб)С(-О)ОНЯ , -M(H)B(-O)VYA, 0 -M(Veg)B(-O) No, -M(H)B(-0)28Y, -M(Neg)5(-0)286, -М-5(-0О)(Нба)ВАех -ОНЯ, -О(С0-0)Н85, -О(С-О)М(Нег) Бе», -0(0-00Н85, -5186, -5 (-0)85, -5(-О3М(Н)ИНА, -5(-О)М(НЯ)ВЯ», -5(-0)289, -5(-0)2М(Н) Va, - (-0)2M(Vza)Ve, -5(-0-M Ag);

Vo means a hydrogen atom, or C:-Cv-alkyl, -«"CHn)n-C2-Cv-alkenyl, -"CHn)p-C2-Cv-alkynyl, -"CH?e)t-

C3-Ce-cycloalkyl, -(CHg)t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-C1-Cv-alkyl, halo-C1-Cv-alkyl, Kba(Be») M-C1-Cv-alkyl, HO-C:-Cv-alkyl, -C1-Cv-alkyl-CM, Ci-Cv-Alkoxy-C1-

C1-alkyl, halo-C1-C1-alkoxy-C1-C1-alkyl, C3-C8-cycloalkyl, 3-7-membered heterocycloalkyl, Cg-

C8-alkenyl-, C4--C8-cycloalkenyl-, C8-C8-alkynyl-, aryl- or heteroaryl; where Ci-Cv-alkyl, -(CHg)n-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-membered heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-C1-Cv-alkyl, halo-Ci-Cv-alkyl, Rhea(Bev)M-C1-Cv-alkyl,, HO- C1-Cv-alkyl, -C1-Cv-alkyl-CM, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, C3-Cv-cycloalkyl, and 3- 7-membered heterocycloalkyl, Ca-Cv-cycloalkenyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2,

With or 4 E8 groups;

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C--

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kea(Nev)M-C1-Cv-alkyl, HO- C:1-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-0О)НЭ, -ФЩ(-ОМ(Н)АЯа, -С(-О)М( Vta)Ve, -C(-0)0-86, -M(Vba)Ve", -MO", -M(H)C(-O)H8e, -M(Neg)C(-O)8e, -МН)С(-О)М(На)Ве, "(Не С(-О)М(Ата)Ве, -М(Н)С(-О)ОВе, -М(Не)С(-ООНВе, -МЩ(Н)(-ОНе, -М(Нбг)5(-0)Н8Я, -М(Н)Б(-О0)28?, -М(Нбг)5(-0)2НА, -М-5 (-О)(Н)ВА -ОВ8б, 0 -О(0-О)В8е, -О(С-О)М(Неа)ВЯ» -О(0-0)0ОН?, -586, -5( -0)Н88, -5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, 00 -5(-0)2М(Н)АЯ, -5(-0)2М(Вба)Бе», -5(-0)(-МНЯ)НЯ; where the indicated C-Cv- alkoxy-, aryl- or heteroaryl is optionally substituted, identically or differently, 1 . in the ortho position to each other on the aryl ring, the indicated 2 K" groups together form a bridge: "О(СнгГЬО" "СОСНУ" "МН(С(-О))МН", where " means the place of attachment to the specified aryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, vea(He)M-C1-Cv-Alkyl, HO-C.i-Cv -alkyl, C1-Cv-Alkoxy-Ci-Cv-alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, Co-Cv-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, - С(-0)НЕ, -ФЩ(-ОМ(Н)АЯа, -С(-О)М(Вта)Ве, -С(-0)0-86, -М(Вба)Ве», -MO» . )Be, -M(Н)С(-О)ОБе, -М(Не)С(-ООНБе, -МЩ(Н)(-ОНе, -М(Нбс)5(-0)Н5, -М(Н )B(-0)285, -M(Nes)B(-0)2Нб, -М-5(-О)(Нба)НЯВ -0Нб 0 -О(0-0)Н, -О(С-О )М(Нба)неЯ» -О(С0-0)ОНе, -52я58, -5(-0)Н5, -5(-0)М(Н)Н5, -5(-0)М(Нба)Ве , -5(-0)2H56, -5(-0)2MZh(H)He, -5(-0)2M(Nea)Be, -5(-03(-MNes)AE or -5(-0 2-(3-7-membered heterocycloalkyl); where the indicated 3-7-membered heterocycloalkyl- or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyl; t means an integer 0, 1, 2, 3, 4, 5 or 6; n is an integer 0, 1, 2, 3, 4 or 5;

X is 5, 5(50), 5(20)2, O, MH; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

In another preferred embodiment, the invention relates to a compound of the general formula |, above, where:

вя, в'? takes 7 days

A means; where " indicates the place of attachment of the specified groups to the molecule; 2 means -С(-О)М(Н)А: or -С(-5Х(Н) 2, or a group selected from ши Y; M m shk - - у у « -- ЖК ra В ЖК y y 2 2 2 М M

V A N i N 5 , , , , ,

Comrade A

M and HOM. this is MU Mn a i -k -k In i x-

M 2 2 "! - 2

H v v --kM; where " indicates the place of attachment of the indicated groups to the molecule;

B means a hydrogen atom, or C.i-Cv-alkyl, halo-C1-Cv-alkyl, Bba(8bv)M-C-Cv-alkyl, HO-C1-Cv-alkyl, -C1-Cv-alkyl-" CM, C1-Cv-Alkoxy-Ci-Cv-alkyl, halo-Ci-Cv-Alkoxy-Ci-Cv-alkyl, C2-Cv-alkenyl-, Co-Cv-alkynyl- or C3-Cv-cycloalkyl-; where the indicated C3-Cv-cycloalkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 - groups selected from: halogen, OH, -CM, C1-Cv-alkyl, -C1-Cv- alkoxy, halo-C1-C1-alkyl-;

BZ means a hydrogen atom or a halogen atom, or -CM, C1-Cv-alkyl, -C1-Cv-alkoxy, -(CHg)t-Seg-

C-alkenyl, /-(CHg)t-C4-Cv-cycloalkenyl, /-(CHg)t-C2-Cv-alkynyl, /-«("CNeg)t-C3-Cv-cycloalkyl, 15. -(CHe )t-(3-7-membered heterocycloalkyl), -(CHg)t-(4-8--membered heterocycloalkenyl), aryl-C1-Cv-alkyl, heteroaryl-C:-Cv-alkyl, halo-C1-Cv -alkyl, Kba(Bei)M-C1-Cv-alkyl, halo-C1-Cv- alkoxy-C1-Cv- alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cv-alkenyl-, Ca -Св-cycloalkenyl-, С2-

C1-C8-alkynyl-, aryl-, -C1-C8-alkyl-aryl, -C1-C8-alkyl-heteroaryl, heteroaryl-, C1-C8-alkyl-xX-, -X-(CHg)t-C2-Cv- alkenyl, -X-(CHg)t-Ca-Cv-cycloalkenyl, -X-(CHg)t-C2-Cv-alkynyl, -X-(CHg)t-C3-Cv-cycloalkyl, -X-(CHg) t-(3-7-membered heterocycloalkyl), -X-(CHg)t-(4-8-membered heterocycloalkenyl), aryl-Xx-, heteroaryl-Xx-, -C(-0)H8E, -C (-О)М(Н)НяТа, /-С(-О)М(Веа)Ве», --0)0-Не, -М(Вба)Ве», -МО», -МЩ(Н)С (-О)Н8е, -ОНе, -5185, -5(-0)Н86, -5(-0)285, -5(-0)(-МНбаг) Бе, -5(-0)2М(НеБ) Wec, -5-(CHg)p-M(Hba)Be" or -5-(CHg)p-(3-7-membered heterocycloalkyl); where indicated C:i-Cv-alkyl, -C1-Cv-alkoxy, -(CHg)t-C2-Cv-alkenyl, -(CHg)t-C2-Cv-alkynyl, 25: -(CHeg)t-Cz -Cv-cycloalkyl, aryl-Ci-Cv-alkyl, heteroaryl-C1-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, Cg-Cv-alkenyl-, C«-Cv-cycloalkenyl-, Cg -C1-alkynyl-, aryl-, C1-C1-alkyl-X-, /-X-(CHg)t-C2-Cv-alkenyl, /-X-(CHeg)t-Ca-Cv-cycloalkenyl, /- X-(CHn)t-C2-Cv-alkynyl, -X-(CHn)t-C3-Cv-cycloalkyl, -X-(CHn)t-(3-7-membered heterocycloalkyl), -X-(CHn) t-(4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-x-, -C1-C6-alkyl-aryl, -C1-C6-alkyl-heteroaryl or heteroaryl is optionally substituted, identically or differently , 1, 2, 3, 4 or 5 K" groups; да, ДЬ, дея, ДЯ mean, independently of each other, hydrogen or a halogen atom, or -СМ,

Ci-Cv-alkyl, Ci-Cv-Alkoxy-, halo-Ci-Cv-Alkyl, Kba(Nev)M-C1-Cv-Alkyl, HO-C1-Cv-Alkyl, Ci-Cv-Alkoxy-C1-Cv -alkyl, halo-C1-Cv-Alkoxy-C1-Cv-alkyl, -C(-O)H8E, -C(-O)M(H)Aea, -C(-O)M(Nea)Be", -b(-0)0-NE, -M(Be)BE», -MO», -M(Н)С(-О)НЕ, 0 -М(Бе)С(-0)8Е, 0 -Щ (Н)С(-О)М(ВегВе», -М(Вес)с(-О)М(Вег)Ве, -М(Н)С(-0О)ОВЕ, -М(Вег)С(-0 )ОНЕе, -М(Н)В(-О)Бе, 0 -М(Вег)5(-О) Ne, -М(Н)Б(-0)28Я, -М(Neg)5(-0) 286.

-0(С0-00ОН5, -51386, -5(-0)Н5, -5(-0О)М(Н)АН5, -5(-0О)М(Нба)ВНе, -5(-0285, -5 (-0)2M(H)Nva, -5(-0)2M(Nea)Ve, -5(-0)(-MNeg) Ve;

B" means a hydrogen atom, or Ci-Cv-alkyl, -""CHn)p-C2-Cv-alkenyl, -"CHn)p-C2-Cv-alkynyl, -"CHe)t-

C3-Cv-cycloalkyl, -(CHg)t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-C1-Cv-alkyl, halo-C1-Cv-alkyl, Kba(Be») M-C1-Cv-alkyl, HO-C:-Cv-alkyl, -C1-Cv-alkyl-CM, Ci-Cv-Alkoxy-C1-

C1-alkyl, halo-C1-C1-alkoxy-C1-C1-alkyl, C3-C1-cycloalkyl, and 3-7-membered heterocycloalkyl, Cg-

C-alkenyl-, C--Cv-cycloalkenyl-, Cg-Cv-alkynyl-, aryl- or heteroaryl; where Ci-Cv-alkyl, -(CHg)n-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-membered heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-C1-Cv-alkyl, halo-Ci-Cv-alkyl, Kba(Neu)M-C1-Cv-alkyl,, HO-C1- C1-alkyl, -C1-Cv-alkyl-СМ, C1-Cv-Alkoxy-C1-Cv-alkyl, halo-C1-Cv-Alkoxy-C1-Cv-alkyl, C3-Cv-cycloalkyl, and 3-7- membered heterocycloalkyl, Са-Св- cycloalkenyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2,

With or 4 short circuit groups;

Ve, Vba, dDBB, Des mean, independently of each other, a hydrogen atom, or Ci-Cv-alkyl, HO-C-

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bea(Bev)M-Ci-Cv-alkyl,, HO -C.:-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, C2-C1-alkenyl, C-7/-membered heterocycloalkyl, aryl-, heteroaryl-, -С(-0)НЕ6, - c(-О)М(Н)веа, -С(- О)М(Веа)Ве, -2(-0)0-Н8Е, -М(Вба)Ве», -МО», -Ш(Н)С(-О)Ве, -М(В85)0(- O)H8, -

Mm(H)C(-OM(NVa)Nev, -M(Neg)O(-O)M(Aba)Nev, -M(H)C(-O)ONE, -M(Neg)O(-0 )ОНе, -Ж(Н)Б(-О)Н, -

М(Нбс)5(-О0)НЯ, -М(Н)Б(-0)286, -М(Нег)В(-0)2Нб, -М-5(-О)(Нба)ВЯ", - НЕ, -О(0-0)НЕ, (-

О(С-О)М(Неа)Бе», -0(0-0)ОН6, -586, -5(-0)Н8, - 5(-О)М(Н)Н, -5(-0О )M(Nba)Be, -5(-0)2H5, - 5(-0)2M(H)He, -5(-0)2M(Nea)Be" or - 5(-0)(-M Abe ) Ve; where the indicated C:i-Cv-alkoxy-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2 or 3 Ci-Cv-alkyl, Ci-Cv-alkoxy-, halo-C1-Cv- alkoxy-, -C(-0)0-H5 or -OH groups; or when 2 B" groups are present in the ortho position to each other on the aryl ring, the specified 2 B" groups together form a bridge: "О(СнгагБ5О "(СНУ "МН(С(-ОУМНУ), where " means the place of attachment to the specified aryl);

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl,

Vba(de)M-Si-Cv-alkyl, HO-C:-Cv-alkyl, Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, Co-Cv -alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -0(-0)РНЭ, -Ф(-О)М(Н)Нба, -С(-О)М(Неа)Бе» -0(-0)0-Н85, -М(Нба)Бей, -МО», -М(Н)С(-О)Не, -М(Нбе)С(-О)Не, -МН)С( -О)М(На)Нев, -М(Нес)С(-О)М(Аба)Нев, -М(Н)С(-О0)ОНе, -М(Не)С(-0)ОНе, - М(Н)Б(-О)Не, -М(Нбс)5(-0)Н5, -М(Н)Б(-0)285, -М(Нес)Б(-0)2Нб, -М- 5(-О)(Нба)НЯВ -0Нб 0 -О(0-0)Н, -О(С-О)М(Неа)ВЯ» -О(0-0)0ОН?, -586, -5( -0)Н88, -5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, -(-0)2МЩ(Н)Не, -55 -0)2M(Hg)Ve, -5(-0-M A), -5(-0)2-(3-7-membered heterocycloalkyl); where the indicated 3-7-membered heterocycloalkyl- or heteroaryl- is optionally substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyls; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5;

X is 5, 5(50), 5(20)2, O, MH; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

In another preferred embodiment, the invention relates to a compound of the general formula |, above, where:

A means vy , vya 7 works where " indicates the place of attachment of the indicated groups to the molecule; 2 means a-С(-О)М(Н)В:2 or -С(-55Ш( Н)Н2, or a group selected from ше -т0те- -6808К

GO ke Gn U n MU cm MU tm shk - - ey She y , -- ЖК y y --K y her 2 2 2 М M

And in A N i N

Comrade A

MU m rila MN

Ky -m m SA A

M 2 2 "! - 2

N v v - MKX; in , , , , , ; where " indicates the place of attachment of the indicated groups to the molecule;

B means a hydrogen atom, or C.i-Cv-alkyl, halo-C1-Cv-alkyl, Bba(8bv)M-C-Cv-alkyl, HO-C1-Cv-alkyl, -C1-Cv-alkyl-" CM, C1-Cv-Alkoxy-Ci-Cv-alkyl, halo-Ci-Cv-Alkoxy-Ci-Cv-alkyl, C2-Cv-alkenyl-, Co-Cv-alkynyl- or C3-Cv-cycloalkyl-; where the indicated C3-Cv-cycloalkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 - groups selected from: halogen, OH, -CM, C1-Cv-alkyl, -C1-Cv- alkoxy, halo-C1-C1-alkyl-;

BZ means a hydrogen atom or a halogen atom, or -CM, C1-Cv-alkyl, Ci-Cv-alkyl-, -(CHg)t-Seg-

Cn-alkenyl, / -(CNeg)t-C"-Cn-cycloalkenyl o -(CHn)t-Cg2-Cn-alkynyl, /-(CNeg)t-C3-Cn-cycloalkyl, -(CNe)t-( 3-7-membered heterocycloalkyl), -(CNeg)t-(4-8-membered heterocycloalkenyl), aryl-C1-Cv-alkyl, heteroaryl-C:-Cv-alkyl, halo-C1-Cv- alkyl, Kba(Bei)M-C1-Cv-alkyl, halo-C1-Cv- alkoxy-C1-Cv- alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cv-alkenyl-, Ca- С-cycloalkenyl-, C2-

C1-C8-alkynyl-, aryl-, -C1-C8-alkyl-aryl, -C1-C8-alkyl-heteroaryl, heteroaryl-, C1-C8-alkyl-xX-, -X-(CHg)t-C2-Cv- alkenyl, -X-(CHg)t-Ca-Cv-cycloalkenyl, -X-(CHg)t-C2-Cv-alkynyl, -X-(CHg)t-C3-Cv-cycloalkyl, -X-(CHg) t-(3-7-membered heterocycloalkyl), -X-(CHg)t-(4-8-membered heterocycloalkenyl), aryl-X-, heteroaryl-X-, -C(-0)Hb, -C (-О)М(Н)НЯа, -С(/-0О)М(Нег)де», --0)0-Не, -М(Вба)Ве», -МО», -МЩ(Н)С (-О)Н8е, -ОНе, -5185, -5(-0)Н86, -5(-0)285, -5(-0)(-МНбаг) Бе, -5(-0)2М(НеБ) Wec, -5-(CHg)p-M(Hba)Be" or -5-(CHg)p-(3-7-membered heterocycloalkyl); where indicated C:i-Cv-alkyl, -C1-Cv-alkoxy, -(CHg)t-C2-Cv-alkenyl, -(CHg)t-C2-Cv-alkynyl, -(CH2g)t-C3-Cv -cycloalkyl, aryl-Ci-Cv-alkyl, heteroaryl-C1-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cv-alkenyl-, C4-Cv-cycloalkenyl-, C2-Cv- alkynyl-, aryl-, C1-Cv-alkyl-X-, /-X-(CHg)t-C2-Cv-alkenyl, /-X-(CHeg)t-Ca-Cv-cycloalkenyl, /-X-( SNc)t-C2-Cv-alkynyl, -X-(CHn)t-C3-Cv-cycloalkyl, -X-(CHn)t-(3-7-membered heterocycloalkyl), -X-(CHn)t-( 4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-x-, -C1-Cv-alkyl-aryl, -C1i-Cv-alkyl-heteroaryl or heteroaryl is optionally substituted, identically or differently, 1, 2, 3, 4 or 5 K" groups; or

Для, Дт, ДЯ mean a hydrogen atom, and

A" means a hydrogen atom or a halogen atom or C.1-Cv-alkyl; or

Ve, De, ДЯ mean a hydrogen atom, and

And: means a halogen atom or C:-Cv-alkyl, -ONE, -0О(С-О)Н, -О(0-О)М(Вег)Бе, -(0-О)ОНБе, -585, - 5(-0)88, -B(--ОЖМ(Н) Ne, -(-О)М(Вег)Бе», -5(-0)286, -5(-0)2М(Н) Ba, -5(-0)2М(Бе2) Ве", -(-ОХ-Мае) Ne;

B" means a hydrogen atom, or Ci-Cv-alkyl, -""CHn)p-C2-Cv-alkenyl, -"CHn)p-C2-Cv-alkynyl, -"CHe)t-

C3-Ce-cycloalkyl, -(CHg)t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-C1-Cv-alkyl, halo-C1-Cv-alkyl, Kba(Bei)M -C1-Cv-alkyl, HO-C1-Cv-alkyl, -C1-Cv-alkyl-CM, C1-Cv-Alkoxy-C1-

C1-alkyl, halo-C1-C1-alkoxy-C1-C1-alkyl, C3-C1-cycloalkyl, and 3-7-membered heterocycloalkyl, Cg-

C-alkenyl-, C--Cv-cycloalkenyl-, Cg-Cv-alkynyl-, aryl- or heteroaryl; where Ci-Cv-alkyl, -(CHg)n-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-membered heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-C1-Cv-alkyl, halo-Ci-Cv-alkyl, Rhea(Bev)M-C1-Cv-alkyl,, HO- C1-Cv-alkyl, -C1-Cv-alkyl-CM, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, C3-Cv-cycloalkyl, and 3- 7-membered heterocycloalkyl, Ca-Cv-

cycloalkenyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2,

With or 4 short circuit groups;

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C--

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bea(Bev)M-Ci-Cv-alkyl, HO- S.: -Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-О)НЕ, -Ф(-О)М(Н)Нба, -С(-О) M(Nea)Be", -0(-0)0-H85, -M(Nba)Be, -MO", -M(H)C(-O)He, -M(Nbe)C(-O) Ne, -МН)С(-О)М(На)Нев, -М(Нес)С(-О)М(Аба)Нев, -М(Н)С(-О0)ОНе, -М(Не)С (-0)ОНе, -М(Н)Б(-О)Не, -М(Нбс)5(-0)Н5, -М(Н)Б(-0)285, -М(Нес)Б(- 0)2Нб, -М-5(-О)(Нба)НЕВ -0Нб 0 -О(0-0)Н, -О(С-О)М(Нба)неЯ» -О(С0-0)ОНе, -52я58, -5(-0)Н5, -5(-0)М(Н)Н5, -5(-0)М(Нба)Бей, -5(-0)2Н56, -(-0)2М( H) He, -55-0)2M(Nea)Bei, -5(-0(-M es) He; where the indicated C:1-C8-alkoxy-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2 or with C.i.i.-Cv-alkyl, C.i.-Ci-Cv-alkyl, C.i-Ci-Cv-alkyl, halo-Ci-Ci-Cv-alkoxy-, -C(-0)0-HE or -OH groups; or when 2 B "groups are present in the ortho position to each other on the aryl ring, the indicated 2 EC" groups together form a bridge: "О(СнггЬО" "СОСНУ" "МН(С(-О))МН", where " means the place of attachment to the indicated aryl rings;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl,

Vba(de)M-Si-Cv-alkyl, HO-C:-Cv-alkyl, Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, Co-Cv -alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -0(-0)РНЭ, -Ф(-О)М(Н)Нба, -С(-О)М(Неа)Бе» -0(-0)0-Н85, -М(Нба)Бей, -МО», -М(Н)С(-О)Не, -М(Нбе)С(-О)Не, -МН)С( -О)М(На)Ве, «(Не С(-О)М(Ата)Ве, -М(Н)С(-О)ОВе, -М(Не)С(-ООНВе, -МЩ(Н) (-ОНе, -М(Нбг)5(-0)Н8Я, -М(Н)Б(-О0)28?, -М(Нбг)5(-0)2НА, -М-5(-О)( Н)BA -ОВ8б, 0 -О(0-О)В8е, -О(С-О)М(Неа)ВЯ» -О(0-0)0ОН?, -586, -5(-0)Н88, -5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, -(-0)2МЩ(Н)Не, -55-0)2М( Hg)Ve, -5(-0-MA), -5(-0)2-(3-7-membered heterocycloalkyl); where the indicated 3-7-membered heterocycloalkyl- or heteroaryl is optionally substituted , identically or differently, 1, 2, C or 4 C-Cv-alkyl-; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5;

X is 5, 5(-50), 5(-0)2, O, MA; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

In another preferred embodiment, the invention relates to a compound of the general formula |, above, where: в': , d'? takes 7 days

A means; where " indicates the place of attachment of the specified groups to the molecule; 2 means -C(-O)M(H)B2 or -C(-5)MSH(H)B, or a group selected from yt-8y-t-6- then

Hn on Kn MU cm MU cm

MI sho sho ey u u same ZhK y V ZhK y y 2 2 2 M M

In A N I N

Comrade A

M m rila MN

Kit M -k S A

M 2 2 " ! -M 2

N v v -- M . where " indicates the place of attachment of the indicated groups to the molecule;

IN? means a hydrogen atom, or C.i-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bev)M-C-Cv-alkyl, HO-C1-Cv-alkyl, -C1-Cv-alkyl-CM, C1-Cv-Alkoxy-C1-Cv-Alkyl, Halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, C1-Cv-Alkenyl-; C2-C6-alkynyl- or C3-C6-cycloalkyl; where the indicated C3-C8-cycloalkyl is optionally substituted, identically or differently, by 1, 2, 3 or 4 groups selected from: halogen, OH, -CM, C1-C8-alkyl, -C1-C8-alkyl , halo-C1-C1-alkyl;

BZ means a hydrogen atom or a halogen atom, or -CM, C1-Cv-alkyl, -C1-Cv-alkoxy, -(CHg)t-Seg-

Cn-alkenyl, -(CNeg)t-C4-Cn-cycloalkenyl o -(CNeg)t-C2-Cn-alkynyl, -(CNeg)t-C3-Cn-cycloalkyl, -(CNe)t-(3- 7-membered heterocycloalkyl), -(CNeg)t-(4-8-membered heterocycloalkenyl), aryl-C1-Cv-alkyl, heteroaryl-C:-Cv-alkyl, halo-C1-Cv-alkyl, Kba(Ve)M-C1-Cv-alkyl, halo-C1-Cv-alkyl-C1-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cv-alkenyl-, Ca-Cv- cycloalkenyl-, C2-

C1-C8-alkynyl-, aryl-, -C1-C8-alkyl-aryl, -C1-C8-alkyl-heteroaryl, heteroaryl-, C1-C8-alkyl-xX-, 15. -X-(CNeo)t-C2- Св-alkenyl, -Х-(СНег)т-Са-Св-cycloalkenyl,. -X-(CHg)t-C2-Cv-alkynyl, -X-(CHg)t-C3-Cv-cycloalkyl, -X-(CHg)t-(3-7-membered heterocycloalkyl), -X- (CHg)t-(4-8-membered heterocycloalkenyl), aryl-Xx-, heteroaryl-Xx-, -C(-0)H8E, -C(-O)M(H)NYA, /-C(-O )М(Веа)Ве», -(-03)0-Не, -М(Вба)Ве», -МО», -Ш(Н)С(-О0)Не, -Оов8е, -5185, -5( -0O)He, -5(-0)2H85, -5(-0(-M Aa), -5(-0)2M(HeB) Ves, -5-(CHg)p-M(Hba) Be» or -5-(CH2)p-(3-7-membered heterocycloalkyl); where C:1-C8-alkyl, -C1-C8-alkyl, -(CH8)t-C2-C8-alkenyl, -(CH8 )t-C2-Cv-alkynyl, -(CH2g)t-C3-Cv-cycloalkyl, aryl-Ci-Cv-alkyl, heteroaryl-C1-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, Cg-Cv-alkenyl-, C4-Cv-cycloalkenyl-, Cg-Cv-alkynyl-, aryl-, C1-Cv-alkyl-X-, /-X-(CHg)t-C2-Cv-alkenyl, /- X-(CHn)t-Ca-Cv-cycloalkenyl, /-X-(CHng)t-C2-Cv-alkynyl, -X-(CHn)t-C3-Cv-cycloalkyl, -X-(CHn)t- (3-7-membered heterocycloalkyl), -X-(CHg)t-(4-8-membered heterocycloalkenyl), aryl-x-, heteroaryl-x-, -C1-Cv-alkyl-aryl, -C1i-Cv- alkyl-heteroaryl or heteroaryl is optionally substituted, identical or in different, 1, 2, Z, 4 or 5 KE" groups; or

Vl, De, ДЯ mean a hydrogen atom, and

A" means a hydrogen atom or a halogen atom or C.1-Cv-alkyl; or

В, Дие, ДЯ mean a hydrogen atom, and

Da means a halogen atom or C1-Cv-alkyl- or -ОНе С)УНЕ, -О(С-О)М(а)Бей, -0(С-О)ОНУ, - 58, -5(-0)85 . )Ve", -(-0)(-MAeg)re;

B" means a hydrogen atom, or Ci-Cv-alkyl, -(CHg)t-(3-7-membered heterocycloalkyl), aryl- or heteroaryl; the indicated C-C-alkyl, -(CHg)t-(3-7--lene heterocycloalkyl), aryl- or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 EZ groups;

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C--

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kea(Nev)M-C1-Cv-alkyl, HO- C:1-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-ОО)НЕ, -б(-ОМ(Н)Веа, -С(-ОМ(Вег) Veh, -C(-0)0-8e, -M(Veg)Ve", -MO", -M(H)C(-O)85, -M(Veg)C(-ОВ8, -M(H )С(-О)М(Вег)вее, -М(Вес)С(-О)М(Веа)Вее, -Ж(Н)С(-О)ОВе, -М(Ве)с(-0) О8е, -ШХН)В(-ОВе, -М(Вег)5(-0)8Е, -М(Н)Я(-0)28Е, -М(Бе5(-0)286, -М-5(- О)(Бе)Бе, -ОБе, 0 -О(С-О)8е,

-О(С-О)М(Нба)неЯ» -О(С0-0)ОНе, -52я58, -5(-0)Н5, -5(-0)М(Н)Н5, -5(-0 )M(Nba)Ve, -5(-0)2Н56, -(-0)2М(Н) Ne, -55-0)2M(Nea)Ve, -5(-0(-Мес) Ne; where the specified C:i-Cv-alkyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2 or 3 Ci-Cv-alkyl, Ci-Cv-alkoxy-, halo-C1-Cv-alkyl -, -C(-0)0-H5 or -OH groups; or when 2 B" groups are present in the ortho position to each other on the aryl ring, the specified 2 B" groups together form a bridge: "О(СНнг)2»65О , "О(СНгЮ" "МН(С(-О))МН", where " means the point of attachment to the specified aryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl,

Vba(de)M-Si-Cv-alkyl, HO-C:-Cv-alkyl, Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, Co-Cv -alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -0(-0)РНЭ, -Ф(-О)М(Н)Нба, -С(-О)М(Неа)Бе» -0(-0)0-Н85, -М(Нба)Бей, -МО», -М(Н)С(-О)Не, -М(Нбе)С(-О)Не, 15. -МЩ( H)C(-O)M(Hg)BeB, "(He C(-OM(Bta)Be, -M(H)C(-OOBe, -M(He)C(-ООНBe, -МЩ(Н) Б(-О No, -М(Нбг)5(-0)Н8Я, -М(Н)Б(-О0)28?, -М(Нбг)5(-0)2НЯ, -М-5(-О )(Н)ВА -ОВ8б, 0 -О(0-О)В8е, -О(С-О)М(Неа)ВЯ» -О(0-0)0ОН?, -586, -5(-0) Н88, -5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, -(-0)2МЩ(Н)Не, -55-0) 2M(Hg)Ve, -5(-0-MA), -5(-0)2-(3-7-membered heterocycloalkyl); where the specified 3-7-membered heterocycloalkyl- or heteroaryl is optional substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyl; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5;

X is 5, 5(-0), 5(-0)2, O, MH; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

UMO 2011/013729A1 describes IC50 values for inhibition of Mr5-1 (TTK) for a pair of compounds of formula C1, above. However, MO 2011/013729A1 does not provide any information regarding the metabolic stability of the compounds.

The inventors of this invention have unexpectedly discovered that the compounds of the general formula I, above, where BZ means aryl-X- or heteroaryl-X-, and where at least one of the groups Ks and 2? is not a hydrogen atom, exhibit high inhibitory activity, as well as significant metabolic stability.

Therefore, in another preferred embodiment, the invention relates to a compound of the general formula

And: in? not 2 Mn

Day 3 / in M

AND

Eat where:

And what does vya, v' mean? where "7" indicates the place of attachment of the specified groups to the molecule; 2 means -С(-О)М(Н)А: or -С(-55М(Н) 2;

IN? means a hydrogen atom, or Ci-Cv-alkyl- or C3-Cv-cycloalkyl-; where the indicated C:i-Cv-alkyl- or C3-Ci-cycloalkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 groups selected from: halogen, -OH, -CM, -C1 -C1-alkyl, -C1-C1-alkoxy;

BZ means aryl-X or heteroaryl-X or

Fo, where 7 means the point of attachment of the specified group to the molecule; where aryl-X-, heteroaryl-X or group is indicated

C are optionally substituted, identically or differently, 1, 2, 3, 4 or 5 K" groups; да, ДБ, де, ДЯ mean, independently of each other, a hydrogen or a halogen atom, or -СМ, -OH, S.: -Cv-alkyl, C1-Cv-alkyl, halo-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Nea

HO-C:-Cv-alkyl, MO-C1-Cv-alkyl, Ci-Cv-Alkoxy-C1-Cv-alkyl, halo-C1-Cv-Alkoxy-C1-Cv-alkyl-; provided that at least one of the groups B" and Bs is not a hydrogen atom;

IN? means a hydrogen atom, or Ci-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CnHg )t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bei)M-C1-Cv-alkyl, HO- S.:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cv-alkenyl-, C4-Cv- cycloalkenyl-, C1-C8-alkynyl-, aryl- or heteroaryl; specified C-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-ene heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kba(Nev)M-C1-Cv-alkyl, HO-C1- C1-Alkyl, -C1-C1-Alkyl-CM, C1-C1-Alkoxy-C1-C1-Alkyl, halo-C1-

C1-Alkoxy-C1-C8-alkyl, C3-C8-cycloalkyl, 3-7-membered heterocycloalkyl, C4-C8-cycloalkenyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2 , With or 4 8 groups;

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C.1-Cv-alkyl, HO-C--

C1-alkyl, C3-C8-cycloalkyl, Co-C8-alkenyl, 3-7-ene heterocycloalkyl, aryl, heteroaryl,

C0 /aryl-C:-C1-alkyl- or heteroaryl-C:-C1-alkyl-;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, Bba(Bev)M-Ci-Cv-Alkyl, HO- Ci-Cv-alkyl, H2M-Ci-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-alkyl, halo-Ci-Cv-alukoxy-Ci-Cv-alkyl, Co-Cv-alkenyl, 3-7- membered heterocycloalkyl, aryl-, heteroaryl-, -С(-0)Н8б, -С(-0О3)М(Н)НТа, /-С(-О)1М(Нба)ВНе», -С(-0)0 -H5, -M(Nba)Be", /-MO", -MSH(NIS(-O)Be, -M(Veg)C(-0)8Э, -MSH(H)C(-O)M( Ве)ВЭе, -М(Вег)С(-О)М(Ве)Ве», -МЩ(Н)С(-ООНВУ, -М(Вег)С(-О0)О 5, -ЖН)(-О )No, -M(Nbs)5(-0О) No, -МН)Б(-О2Не, -М(Нбс)5(-0)2Н8, -М-5(-0)(Нба)Ве», - ОВНе, -О(0-0)Н5, -О(С-О)М(Нба)АЯ», -О(0-0)ОН8, -58б, -5(-0)Н88,...- 5( -ОМ(Н)Бе, -5(-О)М(Вег)Бе», -5(-0)2Н88, - 5(-0)2М(НБе, -5(-0)2М(Бе2)Бе» or -5(-0X(-MAeg) Ve;

where the specified C-Cv-alukoxy-, aryl-, C3-7--ene heterocycloalkyl or heteroaryl is optionally substituted, identically or differently, by 1, 2 or C:-Cv-alkyl, C-Cv-alkyl -, halo-C1-Cv-alkoxy-, -C(-0)0-HE or -OH groups; or when 2 K" groups are present in the ortho position to each other on an aryl or heteroaryl ring, the specified 2 B" groups together form a bridge: )СНе", "МН(С(-О)МНУ, "Ф(Н)-Ф(Н)-Ф(-0)-МЩ(НУ, where 7" means the place of attachment to the specified aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, -OH, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, Kea(Nev)M-C1-Cv-Alkyl, HO-C: 1-Cv-alkyl, Ci-Cv-Alkoxy-C1-Cv-Alkyl, Halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-О)НЭ, -Ф(-О)М(Н)Нба, -С(-О) M(Nea)Be", -0(-0)0-H85, -M(Nba)Be, -MO", -M(H)C(-O)He, -M(Nbe)C(-O) Ne, -МН)С(-О)М(На)Нев, -М(Нес)С(-О)М(Аба)Нев, -М(Н)С(-О0)ОНе, -М(Не)С (-0)ОНе, -М(Н)Б(-О)Не, -М(Не)5(-0)Нб, -М(Н)Б(-О0)285, -М(Нбг)5(- 0)285, -М-5(-О)(Н)ВАў -ОВ8б, 0 -О(0-О)В8е, -О(С-О)М(Неа)ВЯ» -О(0-0)0ОН ?, -586, -5(-0)Н88, -5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, --02ОН, - 5(-0)2MSH(H) He, -(-0)2M(Bea)BeB, -(-OX-MAs)He, -5(-0)2-(3-7-membered heterocycloalkyl); where the specified 3-7-membered heterocycloalkyl or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyls; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5; and

X is 5, (50), 5(-0)2, O, HAS, SvIvbade, C-C1Vbade,

In another preferred embodiment, the invention relates to a compound of formula 5c

And not 2 MN rai d- M zi i / in M

But where:

A means 4a in 4p and in da in 7 4c in where "indicates the place of attachment of the indicated groups to the molecule; 2 means -С(-О)М(Н)А: or -С(-55М(Н) 2;

B2 means a hydrogen atom, or C1-C8-alkyl- or C3-C8-cycloalkyl-; where the indicated C:i-Cv-alkyl- or C3-Ci-cycloalkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 groups selected from: halogen, -OH, -CM, -C1 -C1-alkyl, -C1-C1-alkoxy;

BZ means aryl-X or heteroaryl-X or a group

WITH

,where " means the point of attachment of the indicated group to the molecule; where the indicated aryl-X-, heteroaryl-X or group

C are optionally substituted, identically or differently, 1, 2, 3, 4 or 5 BE" groups;

Ida means hydrogen;

B means hydrogen; one of the groups KE" and Ks represents a hydrogen atom while the other represents a group selected from: halo-, -CM, -OH, C1-C8-alkyl- and C1-C8-alkyl-;

AV? means a hydrogen atom, or Ci-Cv-alkyl, -(CHn)n-C2-Cn-alkenyl, -(CHn)p-C2-Cn-alkynyl, -(CHn)t-C3-Cn-cycloalkyl, -(CnHg )t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bei)M-C1-Cv-alkyl, HO- S.:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cv-alkenyl-, C4-Cv- cycloalkenyl-, C1-C8-alkynyl-, aryl- or heteroaryl; specified C-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-ene heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Nea(de»)M-C1-Cv-alkyl, HO-C .1-Cv-alkyl, -C1-Cv-alkyl-CM, Ci-Cv-Alkoxy-C:-Cv-alkyl, halo-C1-

C1-Alkoxy-C1-C8-alkyl, C3-C8-cycloalkyl, 3-7-membered heterocycloalkyl, C4-C8-cycloalkenyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2 , Z or 4 P groups;

Ve, Vba, dDBB, Des mean, independently of each other, a hydrogen atom, or Ci-Cv-alkyl, HO-C-

C1-alkyl, C3-C8-cycloalkyl, Co-C8-alkenyl, 3-7-ene heterocycloalkyl, aryl, heteroaryl, aryl-C:-C8-alkyl- or heteroaryl-C:-C8-alkyl-;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, Bea(Be)M-Ci-Cv-Alkyl, HO- Ci-Cv-alkyl, H2M-Ci-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-alkyl, halo-Ci-Cv-alukoxy-Ci-Cv-alkyl, Co-Cv-alkenyl, 3-7- membered heterocycloalkyl, aryl-, heteroaryl-, -С(-0)85, -С(-0)М(Н)НТ, -С(-0О)М(НАа)Бе» -0(-0)0-НЕ . М(Не)С(-О)М(ва)Вев, -(Н)С(-ООВ, -М(Нес)(-О)О Не, -МЖН)(-О)Не, -М(Нбс) 5(-0О) Ne, -МН)Б(-О2Н, -М(Нбс)5(-0)2Н5, 0 -М-5(-0)(Нба)Не», -ОНб, -0(0- 0)Н8, -О(С-О)М(Нба)Не», -О(С0-0)ОН5, -541386, -5(-0)Н6, (- 5(-О)М(Н)Не . 0)(-M Ag); where the indicated C-Cv-alkyloxy-, aryl-, C3-7/--ene heterocycloalkyl or heteroaryl is optionally substituted, identically or differently, by 1, 2 or C.:- C 1 -alkyl, C 1 -C 1 -alkoxy-, halo-C 1 -C 1 -alkoxy-, -C(-0)0-HE or -OH groups; or when 2 E" groups are present in the ortho position to each other on the aryl or hey teroaryl ring, the indicated 2 B" groups together form a bridge: "O(СНng Го", "Оо(СНгО), ""Сна«СНгаМНУ, "СбнгснНгм(вег)СНе", "МН(С(-О))МНУ, "F(n)-F(H)-O(-0)-Щ(НУ, where " means the place of attachment to the indicated aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, -OH, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, Kea(Nev)M-C1-Cv-Alkyl, HO-C: 1-Cv-alkyl, Ci-Cv-Alkoxy-C1-Cv-Alkyl, Halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-О)НЭ, -Ф(-О)М(Н)Нба, -С(-О) M(Nba)Ve, -0(-0)0-H85, -M(Nba)Ve, -MO», -M(H)C(-O)He, -M(Nbe)C(-O) No , -МЩН)С(-О)М(Нба)АеБ, -М(Нес)С(-О)М(Аба)Бей, -М(Н)С(-О)ОНе, -М(Не)О( -О)ОНе, -ЖХ(Н)Б(-О)Не, -М(Нбс)5(-0)Н5, -М(Н)Б(-0)285, -М(Нес)Б(-0 )2Нб, -М-5(-О)(Нба)НЯВ -0Нб 0 -О(0-0)Н, -О(С-О)М(Неа)ВЯ» -О(0-0)0OH?, -586, -5(-0)Н88, -5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, -5-0)2ОН, -5(-0)2M(H)He, -(-0)2M(Bea)BeB, -(-OX-MAs)He, -5(-0)2-(3-7-membered heterocycloalkyl);

where the specified 3-7-membered heterocycloalkyl or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyls; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5; and

X is 5, 5(50), 5(50)2, O, MAE, Sveare, S-Sveade,

In another preferred embodiment, the invention relates to a compound of formula 5

IN

And not 2 MN and d-M

And m

In M

AND

And where:

A means yes

IN

4 years In yes

At 7 4 p.m

Where "indicates the place of attachment of the specified groups to the molecule; 2 means -С(-О)М(Н)В:2 or -С(-5)М(Н)В;

IN? means C:-C3-alkyl- or C3-C6-cycloalkyl-; where the indicated C:i-C3-alkyl- or C3-C6-cycloalkyl- is optionally substituted, identically or differently, by 1, 2 or C groups selected from: halogen, -OH, -CM, -C1-Cv -alkyl, -C1-Cv-Alkoxy;

BZ means aryl-X or heteroaryl-X or a group

WITH

,where " means the point of attachment of the indicated group to the molecule; where the indicated aryl-X-, heteroaryl-X or group

C are optionally substituted, identically or differently, 1, 2, 3, 4 or 5 BE" groups;

Ida means hydrogen;

B means hydrogen;

one of the KE groups? and Ks represents a hydrogen atom while the other represents a group selected from: halo-, -CM, -OH, C1-C8-alkyl- and C1-C8-alkyl-;

IN? means a hydrogen atom, or Ci-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CnHg )t-(3-7-membered heterocycloalkyl), aryl-Ci-Ci-alkyl, heteroaryl-Ci-Ci-alkyl, halo-Ci-Ci-alkyl, Bba(Beb)M-Ci-Ci-alkyl, HO- S.:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C2-Cv-alkenyl-, C4-Cv- cycloalkenyl-, C1-C8-alkynyl-, aryl- or heteroaryl; specified C-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-ene heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kba(Nev)M-C1-Cv-alkyl, HO-C1- C1-Alkyl, -C1-C1-Alkyl-CM, C1-C1-Alkoxy-C1-C1-Alkyl, halo-C1-

C1-Alkoxy-C1-C8-alkyl, C3-C8-cycloalkyl, 3-7-membered heterocycloalkyl, C4-C8-cycloalkenyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2 , Z or 4 P groups;

Ve, Vba, dDBB, Des mean, independently of each other, a hydrogen atom, or Ci-Cv-alkyl, HO-C-

C1-alkyl, C3-C8-cycloalkyl, C2-C8-alkenyl, 3-7-ene heterocycloalkyl, aryl, heteroaryl, aryl-C:-C8-alkyl- or heteroaryl-C:-C8-alkyl-;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, Bea(Be)M-Ci-Cv-Alkyl, HO- Ci-Cv-alkyl, H2M-Ci-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-alkyl, halo-Ci-Cv-alukoxy-Ci-Cv-alkyl, Co-Cv-alkenyl, 3-7- membered heterocycloalkyl, aryl-, heteroaryl-, -С(-0)85, -С(-0)М(Н)НТ, -С(-0О)М(НАа)Бе» -0(-0)0-НЕ . . )5(-0О) He, -МН)Б(-О)2Н, -М(Нбс)5(-0)2Н8, -М-5(-О)(Нба)Не», -ОНе, -0( С0-0)Н8, -О(С-О)М(Нба)Не, -О(С-0)ОНЯ, -54185, -5(-0)Н6, (- 5(-О)М(Н) No, -5(-O)M(Nva)Ve, -5(-0)2H86, - 5(-0)2M(H) No, -5(-0)2M(Nea) No" or -5( -0)(-МАг); where the specified C-Cv-alukoxy-, aryl-, C3-7-ene heterocycloalkyl or heteroaryl is optionally substituted, identically or differently, by 1, 2 or C C.:- C 1 -alkyl, C 1 -C 1 -alkoxy-, halo-C 1 -C 1 -alkoxy-, -C(-0)0-HE or -OH groups; or when 2 E" groups are present in the ortho position to each other on the aryl or Mr to the heteroaryl ring, the indicated 2 K" groups together form a bridge: "О(СНнго), "Оо(СНгО), "бнуаСНгиаМНУ, "СбнгснНгм(вег)СНе", "МН(С(-О))МНУ, "Ф( n)-F(H)-O(-0)-Щ(НУ, where 7" means the point of attachment to the indicated aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, -OH, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, Kea(Nev)M-C1-Cv-Alkyl, HO-C: 1-Cv-alkyl, Ci-Cv-Alkoxy-C1-Cv-Alkyl, Halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-О)НЭ, -Ф(-О)М(Н)Нба, -С(-О) M(Nea)Be", -0(-0)0-H85, -M(Nba)Be, -MO", -M(H)C(-O)He, -M(Nbe)C(-O) Not, -МН)С(-О)М(На)Ве, «(Не С(-О)М(Ата)Ве, -М(Н)С(-О)ОВе, -М(Не)С(- ООНВе, -МЩ(Н)(-ОНе, -М(Нбг)5(-0)Н8Я, -М(Н)Б(-О0)28?, -М(Нбг)5(-0)2НЯ, -М -5(-О)(Н)ВА -ОВ8б, 0 -О(0-О)В8е, -О(С0-О)М(Нба)Ве», -О(0-0)0Н?, -5НЕ, -5(-0)Н88, -5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, -5-0)2ОН, -5( -0)2M(H)He, -(-0)2M(Bea)BeB, -(-OX-MAs)He, -5(-0)2-(3-7-membered heterocycloalkyl); where the indicated 3- 7-membered heterocycloalkyl- or heteroaryl is optionally substituted, identically or differently, with 1, 2, C or 4 C-Cv-alkyl; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4, or 5; and

X is 5, 5(50), 5(20)2, O, MAE, Sneade, S-Svbade,

In another preferred embodiment, the invention relates to a compound of formula VI

I ns 2 MN and d- M

And miy vi M

AND

And where:

A means da vi 4r and vi da vi 7 4s vi 5 ; where " indicates the place of attachment of the specified groups to the molecule; 2 means -С(-О)М(Н)А: or -С(-55М(Н) 2;

IN? means C:-C3-alkyl- or C3-C6-cycloalkyl-; where the indicated C:i-C3-alkyl- or C3-C6-cycloalkyl- is optionally substituted, identically or differently, by 1, 2 or C groups selected from: halogen, -OH, -CM, -C1-Cv -alkyl, -C1-Cv-Alkoxy;

BZ means a group selected from the following: phenyl-X, quinolinyl-X-, pyridyl-x-, thienyl-X-, pyrazinyl-x-, imidazyl-x-, triazyl-x-, pyrazyl-x- and

WITH

; where the specified group is optionally substituted, identically or differently, by 1, 2, 3, 4 or 5 B" groups;

Ida means hydrogen;

B means hydrogen; one of the groups P» and c represents a hydrogen atom, while the other represents halo- or C:-C 1 -alkyl-;

AV? means a hydrogen atom, or Ci-Cv-alkyl, -(CHn)n-C2-Cn-alkenyl, -(CHn)p-C2-Cn-alkynyl, -(CHn)t-C3-Cn-cycloalkyl, -(CnHg )t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bei)M-C1-Cv-alkyl, HO- S.:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, Cg-Cv-alkenyl-, C4-Cv- cycloalkenyl-, C1-C8-alkynyl-, aryl- or heteroaryl; specified C-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-ene heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(de»)M-C1-Cv-alkyl, HO-C .1-Cv-alkyl, -C1-Cv-alkyl-CM, Ci-Cv-Alkoxy-C:-Cv-alkyl, halo-C1-

C1-Alkoxy-C1-C8-alkyl, C3-C8-cycloalkyl, 3-7-membered heterocycloalkyl, C4-C8-cycloalkenyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2 , with or 4 KU groups;

Ve, Vba, dDBB, Des mean, independently of each other, a hydrogen atom, or Ci-Cv-alkyl, HO-C-

C1-alkyl, C3-C8-cycloalkyl, Co-C8-alkenyl, 3-7-ene heterocycloalkyl, aryl, heteroaryl, aryl-C:-C8-alkyl- or heteroaryl-C:-C8-alkyl-;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, Bea(Be)M-Ci-Cv-Alkyl, HO- Ci-Cv-alkyl, H2M-Ci-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-alkyl, halo-Ci-Cv-alukoxy-Ci-Cv-alkyl, Co-Cv-alkenyl, 3-7- membered heterocycloalkyl, aryl-, heteroaryl-, -С(-0)85, -С(-0)М(Н)НТ, -С(-0О)М(НАа)Бе» -0(-0)0-НЭ . . )5(-О)He, -МН)Б(-О)2Н, -М(Вбе)5(-0)2Н5, -М-5(-О)(Нба)Не», -ОНе, -0( С0-0)Н8, -О(С-О)М(Нба)Не, -О(С-0)ОНЯ, -54185, -5(-0)Н6, (- 5(-О)М(Н) No, -5(-O)M(Nva)Ve, -5(-0)2H86, - 5(-0)2M(H) No, -5(-0)2M(Nea) No" or -5( -0)(-МАг); where the specified C-Cv-alukoxy-, aryl-, C3-7-ene heterocycloalkyl or heteroaryl is optionally substituted, identically or differently, by 1, 2 or C C.:- C 1 -alkyl, C 1 -C 1 -alkoxy-, halo-C 1 -C 1 -alkoxy-, -C(-0)0-HE or -OH groups; or when 2 E" groups are present in the ortho position to each other on the aryl or here to the aryl ring, the specified 2 B" groups together form a bridge: "О(СНгго", "О(СНаО), "Сна«СНаМНУ, "СбнгснНгм(вег)СНе", "МН(С(-О)МНУ, "С (Н)-С(Н)-С(-0)-М(НУ), where 7" means the place of attachment to the specified aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, -OH, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, Kea(Nev)M-C1-Cv-Alkyl, HO-C: 1-Cv-alkyl, Ci-Cv-Alkoxy-C1-Cv-Alkyl, Halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-О)НЭ, -Ф(-О)М(Н)Нба, -С(-О) M(Nea)Be", -0(-0)0-H85, -M(Nba)Be, -MO", -M(H)C(-O)He, -M(Nbe)C(-O) Not, -МН)С(-О)М(На)Ве, «(Не С(-О)М(Ата)Ве, -М(Н)С(-О)ОВе, -М(Не)С(- ООНВе, -МЩ(Н)(-ОНе, -М(Нбг)5(-0)Н8Я, -М(Н)Б(-О0)28?, -М(Нбг)5(-0)2НЯ, -М -5(-О)(Н)ВА -ОВ8б, 0 -О(0-О)В8е, -О(С-О)М(Неа)ВЯ» -О(0-0)0ОН?, -586, - 5(-0)Н88, -5(-О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, -5-0)2ОН, -5(- 0)2M(H)He, -(-0)2M(Bea)BeB, -(-OX-MAs)He, -5(-0)2-(3-7-membered heterocycloalkyl); where 3-7 is indicated -membered heterocycloalkyl- or heteroaryl is optionally substituted, identically or differently, with 1, 2, C or 4 C-Cv-alkyl; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means integer 0, 1, 2, 3, 4, or 5; and

X is 5, (50), 5(-0)2, O, HAS, SvIvbade, C-C1Vbade,

In another preferred embodiment, the invention relates to a compound of the formula in?

And not 2 MN / Fe k MY

AND

And where:

A means vya, Vie vie 7 does where "indicates the place of attachment of the specified groups to the molecule; 2 means -С(-О)М(Н)А: or -С(-55М(Н) 2;

IN? means C:-C3-alkyl- or C3-C6-cycloalkyl-; where the indicated C:i-C3-alkyl- or C3-C6-cycloalkyl- is optionally substituted, identically or differently, by 1, 2 or C groups selected from: halogen, -OH, -CM, -C1-Cv -alkyl, -C1-Cv-Alkoxy;

BZ means a group selected from the following: phenyl-X, quinolinyl-X-, pyridyl-x-, thienyl-X-, pyrazinyl-x-, imidazyl-x-, triazyl-x-, pyrazyl-x- and

C where the indicated group is optionally substituted, identically or differently, by 1, 2, 3, 4 or 5 B" groups;

ID stands for hydrogen;

B means hydrogen; one of the groups BE" and c means a hydrogen atom, while the other means Ci-Ca-alkyl-;

B means a hydrogen atom, or C:-Cv-alkyl, halo-C1-Cv-alkyl, HO-C1-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl or heteroaryl; specified C:-Cv-alkyl, halo-Ci-Cv-alkyl, HO-C:-Cv-alkyl, , C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, heteroaryl is optionally substituted, identically or differently , 1, 2, Z or 4 VZ groups;

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C--

C1-alkyl, C3-C8-cycloalkyl, Co-C8-alkenyl, 3-7-ene heterocycloalkyl, aryl, heteroaryl, aryl-C:-C8-alkyl- or heteroaryl-C:-C8-alkyl-;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, Bba(Bev)M-Ci-Cv-Alkyl, HO- Ci-Cv-alkyl, H2M-Ci-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-alkyl, halo-Ci-Cv-alukoxy-Ci-Cv-alkyl, Co-Cv-alkenyl, 3-7- membered heterocycloalkyl, aryl-, heteroaryl-, -С(-0)Н8б, -С(-0О3)М(Н)НТа, /-С(-О)1М(Нба)ВНе», -С(-0)0 -H5, -M(Nba)Be», /-MO», -МН)С(-О0)Н, -М(Нег)С(-0)НЯ, -М(Н)С(-О)М( ААа)АеБ, (Абе) С(-О)М(Аба)БеВ, -ЖШЧ(Н)С(-ООНе, 0) -М(нее)С(-О0)О 6, -ЖН(-О)НВ . ОВНе, -О(0-0)Н5, -О(С-О)М(Нба)АЯ», -О(0-0)ОН8, -58б, -5(-0)Н88,...- 5( -OM(H) Be, -5(-O)M(a)Be, -5(-0)285, - (-0)2M(H) Be, -5(-0)2M(892)BE? or -5(-0(-M He) He; where the indicated C-Cv-alukoxy-, aryl-, C3-7-ene heterocycloalkyl or heteroaryl is optionally substituted, identically or differently, 1, 2 or C C.: -Cv-alkyl, Ci-Cv-Alkoxy-, halo-C1-Cv-Alkoxy-, -C(-0)0-HE or -OH groups; or when 2 K" groups are present in the ortho position one to one on the aril or a heteroaryl ring, the indicated 2 K" groups together form a bridge: "O(CHggo", "O(СНаО), ""Сна«СНаМНУ, "снения, "МН(С(-О)МНУ, "С(Н)- С(Н)-С(-0)-М(НУ), where 7" means the place of attachment to the indicated aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, -OH, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, Bea(Bev)M-Ci-Cv-Alkyl, HO-C. :-C1-alkyl, C1-C1-Alkoxy-C1-C1-Alkyl, halo-C1-C1-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-О)НЭ,

-F(-О)М(Н)Нба, -С(-О)М(Неа)Бе», -0(-0)0-Н85, -М(Нба)Бе, -MO», -М(Н )С(-О)Не, -М(Нбе)С(-О)Не, -МН)С(-О)М(На)Нев, -М(Нес)С(-О)М(Аба)Нев, -M(H)С(-О0)ОНе, -М(Не)С(-0)ОНе, -М(Н)Б(-О)Не, -М(Нбг)5(-0)Н8Я, -М (Н)Б(-О0)28?, -М(Нбг)5(-0)2НЯ, -М-5(-О)(Н)ВА -ОВ8б, 0 -О(0-О)В8е, -О (С-О)М(Неа)ВЯ» -О(0-0)0ОН?, -586, -5(-0)Н88, -5(-О)М(Н)АЯ, -5(-О) М(НЯ)АеБ, -5(-0)285, -5-0)2ОН, -5(-0)2М(Н)Не, -(-0)2М(Веа)БеБ, -(-ОХ-МАс )No, -5(-0)2-(3-7-membered heterocycloalkyl); where the specified 3-7-membered heterocycloalkyl or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyls; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5; and

X is 5, (50), 5(-0)2, O, HAS, SvIvbade, C-C1Vbade,

In another preferred embodiment, the invention relates to a compound of formula 5

IN

And not 2 МН and d- M 3 /

In M

AND

And where:

And means

A, сн, where " indicates the place of attachment of the indicated groups to the molecule; 2 means -С(-О)М(Н)В:2 or -С(-5)М(Н)В;

IN? means C:-C3-alkyl- or C3-C6-cycloalkyl-; where the indicated C:i-C3-alkyl- or C3-C6-cycloalkyl- is optionally substituted, identically or differently, by 1, 2 or C groups selected from: halogen, -OH, -CM, -C1-Cv -alkyl, -C1-Cv-Alkoxy;

BZ means a group selected from the following: phenyl-X, quinolinyl-X-, pyridyl-x-, thienyl-X-, pyrazinyl-x-, imidazyl-x-, triazyl-x-, pyrazyl-x- and

C, where the specified group is optionally substituted, identically or differently, by 1, 2, 3, 4, 5, 5 KK" groups;

BZ means a hydrogen atom, or C.: -Cv-alkyl, halo-C1-Cv-alkyl, HO-C1-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl or heteroaryl; specified C:-Cv-alkyl, halo-Ci-Cv-alkyl, HO-C:-Cv-alkyl, , C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, heteroaryl is optionally substituted, identically or differently , 1, 2, Z or 4 BB groups;

Ve, Vba, dDBB, Des mean, independently of each other, a hydrogen atom, or Ci-Cv-alkyl, HO-C-

C1-alkyl, C3-C8-cycloalkyl, Co-C8-alkenyl, 3-7-ene heterocycloalkyl, aryl, heteroaryl, aryl-C:-C8-alkyl- or heteroaryl-C:-C8-alkyl-;

B' means a halogen atom, or HO-, -CM, C:i-Cv-alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, HO-Ci-Cv-alkyl, H2M-Ci-Cv- alkyl, C1-C1-alkenyl, 3-7-ene heterocycloalkyl, -С(-О)М(Н)Веа, -М(Вба)Веј, -Х(Н)С(-О)В? or -585; where the indicated C-C-Alkoxy- or 3-7-membered heterocycloalkyl is optionally substituted, identically or differently, 1, 2 or C C-C-Alkyl, C-C-Alkoxy-, halo-C1-Cv- alkoxy-, -C(-0)0-86 or -OH groups; or when 2 K" groups are present in the ortho position to each other on an aryl or heteroaryl ring, the indicated 2 K" groups together form a bridge: "bnu"CHnhemMn"U, "sna HnHM(va)CHngya "C(H)-C( Н)-С(-0)-М(НУ, where 7" means the place of attachment to the indicated aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, -OH, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, Bea(Bev)M-Ci-Cv-Alkyl, HO-C. :-C1-alkyl, C1-C1-Alkoxy-C1-C1-Alkyl, halo-C1-C1-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-О)НЕ, -ФШ(-ОМ(Н)АЯа, -С(-О)М( Vta)Ve, -C(-0)0-86, -M(Vba)Ve", -MO", -M(H)C(-O)H8e, -M(Neg)C(-O)8e, -МН)С(-О)М(На)Ве, "(Не С(-О)М(Ата)Ве, -М(Н)С(-О)ОВе, -М(Не)С(-ООНВе, -МЩ(Н)(-ОНе, -М(Нег)5(-0)НЯ, -М(Н)Б(-О)285, -М(Нбг)5(-0)285, -М-5( -О)(Н)ВАй -ОВ8б, 0 -О(0-О)8е, -О(С-О)М(Нба)неЯ» -О(С0-0)ОНе, -52я58, -5(-0 )H5, -5(-0)M(H)H5, -5(-0)M(Nba)He, -5(-0)2H56, --02OH, -(-0)2M(H)He, -(-0)2М(Аба)Бе, -(-О3-Мас)Не, -5(-0)2-(3-7-membered heterocycloalkyl); where the indicated 3-7-membered heterocycloalkyl- or heteroaryl is neoob necessarily substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyl; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5; and

X is 5, 5(50), 5(50)2, O, HAS, Sveade, C-sveade,

In another preferred embodiment, the invention relates to a compound of the formula in?

And not 2 Mn / Fe - MM

And from where:

A means and 4 сн, where " indicates the place of attachment of the specified groups to the molecule; 2 means -С(-О)М(Н)А: or -С(-55М(Н) 2;

IN? means C:-C3-alkyl- or C3-C6-cycloalkyl-; where the indicated C:i-C3-alkyl- or C3-C6-cycloalkyl- is optionally substituted, identically or differently, by 1, 2 or C groups selected from: halogen, -OH, -CM, -C1-Cv -alkyl, -C1-Cv-Alkoxy;

BZ means a group selected from the following: phenyl-X, quinolinyl-X-, pyridyl-x-, thienyl-X-, pyrazinyl-x-, imidazyl-x-, triazyl-x-, pyrazyl-x- and

C where the specified group is optionally substituted, identically or differently, by 1, 2, 3, 4 or 5 VK" groups;

BZ means a hydrogen atom, or C.: -Cv-alkyl, halo-C1-Cv-alkyl, HO-C1-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl or heteroaryl; specified C:-Cv-alkyl, halo-Ci-Cv-alkyl, HO-C:-Cv-alkyl, , C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, heteroaryl is optionally substituted, identically or differently , 1, 2, Z or 4 VZ groups;

Whoa, whoa, where. Ddbs mean, independently of each other, a hydrogen atom, or Ci-Cv-alkyl-;

B' means a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl,

HO-C.-Cv-alkyl, H2M-C1-Cv-alkyl, Co-Cv-alkenyl, 3-7-ene heterocycloalkyl, -C(-O)M(H)Vea, 15. -M(Hba) Vev, -ШХН)С(-О)АЭ or -585; where the indicated C-Cv- alkoxy- or 3-7-membered heterocycloalkyl is optionally substituted, identically or differently, 1, 2 or C C-Cv-alkyl, C-Cv-alkyl-, halo-C1- Sv-Alkoxy-, -C(-0)0-86 or -OH groups; or when 2 K" groups are present in the ortho position to each other on an aryl or heteroaryl ring, the indicated 2 B" groups together form a bridge: "bnaСНгзагмн"У, "СнгсНнМм(Бе)СНе", "С(Н)-С(Н )-C(-O)-M(H), where 7" means the point of attachment to the specified aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, -OH, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, Kea(Nev)M-C1-Cv-Alkyl, HO-C: 1-Cv-alkyl, Ci-Cv-Alkoxy-C1-Cv-Alkyl, Halo-C1-Cv-Alkoxy-C1-

C1-alkyl, Co-C1-alkenyl, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С(-О)НЭ, -Ф(-О)М(Н)Нба, -С(-О) M(Nea)Be", -0(-0)0-H85, -M(Nba)Be, -MO", -M(H)C(-O)He, -M(Nbe)C(-O) Ne, -МН)С(-О)М(На)Нев, -М(Нес)С(-О)М(Аба)Нев, -М(Н)С(-О0)ОНе, -М(Не)С (-0)ОНе, -М(Н)Б(-О)Не, -М(Нбс)5(-0)Н5, -М(Н)Б(-0)285, -М(Нес)Б(- 0)2Нb, -М-5(-О)(Нба)НЕВ -0Нб 0 -О(0-0)Н, 0 -О(С0-О)М(Неа)Бе» -О(0-0)0Н ?, -5НЯ, -5(-0)Н88, -5(-0О)М(Н)АЯ, -5(-О)М(НЯ)АеБ, -5(-0)285, --02ОН, - 5(-0)2MSH(H) He, -(-0)2M(Bea)BeB, -(-OX-MAs)He, -5(-0)2-(3-7-membered heterocycloalkyl); where the specified 3-7-membered heterocycloalkyl or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyls; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5; and

X is 5, (50), 5(-0)2, O, HAS, SvIvbade, C-C1Vbade,

MO 2011/013729 JSC describes that the compounds of the formula C1, above, where KZ? means cyclopropyl, are preferred because they tend to be more active in Mp5-1 inhibition than compounds of formula SI, where KZ? does not mean cyclopropyl.

The inventors of this invention unexpectedly found that compounds of formula C1, in which B8 represents a noncyclic group, rather than compounds with cycloalkyl, exhibit high metabolic stability. The inventors of this invention unexpectedly found that compounds of formula C1 exhibit particularly high inhibitory activity against Mp5-1 kinase, if K5 is aryl-X or heteroaryl-xX-, where X is as defined for the compound of formula Y, above.

Thus, the combination when KZ means a non-cyclic group with B means aryl-X or heteroaryl-x- leads to improvement of the inhibitory and metabolic properties of the compounds.

Therefore, in another preferred embodiment, the invention relates to a compound of the formula in? not 2 Mn /Fe x MY

AND

Eat where:

A means in'; , what? in 7 to where 7 means the point of attachment of the specified group to the molecule; 2 means -С(-О)М(Н)А: or -С(-55М(Н) 2;

B2 means a hydrogen atom, or C.:-Cv-alkyl-; where the indicated C:i-Cv-alkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 groups selected from: halogen, -OH, -CM, C1-Cv-alkyl-, C- -Cv-Alkoxy;

BZ means aryl-X or heteroaryl-X, where the specified aryl-X or heteroaryl-X is optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 EC" groups; da, DV, des, DYA mean, independently of each other, hydrogen or a halogen atom, or -CM,

Ci-Cv-alkyl, Ci-Cv-Alkoxy-, halo-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-, Nea(Bev)M-C1-Cv-Alkyl, HO-C:-

C1-alkyl, MSO-C1-C1-alkyl, C1-C1-Alkoxy-C1-C1-Alkyl, halo-C1-C1-Alkoxy-C:1-C1-Alkyl-;

IN? means a hydrogen atom, or Ci-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CH2g)t-C3-Cv-cycloalkyl, -(CHg )t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Ve)M-C1-Cv-alkyl, HO-C.:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C--Cv-cycloalkenyl-, aryl- or heteroaryl; specified C-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-ene heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Nea(de»)M-C1-Cv-alkyl, HO-C .1-Cv-alkyl, -C1-Cv-alkyl-CM, Ci-Cv-Alkoxy-C:-Cv-alkyl, halo-C1-

C1-Alkoxy-C1-C8-alkyl, C3-C8-cycloalkyl, 3-7-membered heterocycloalkyl, C4-C8-cycloalkenyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2 , 3, 4 or 5 K8 groups;

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C--

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kea(Nev)M-C1-Cv-alkyl, HO- C:1-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, C2-C8-alkenyl-, C2-C8-alkynyl-, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -b(-0)H6, -C(-O)M(H) Nba, -С(-О3)М(Нба)ВНе, -С(-03)0-Нб, -М(Нба)Бе», -МО», -М(Н)С(-О)Не, -М (Nbs)C(-0)H88, -MSH(H)C(-O)M(Aba)Aev, -M(Abg)C(-O)M(Nvba)ne», -M(H)IS( -О)ОНе, -М(Нес)С(-OO No,

З5 -М(Н)Б(-О)НА, -М(НЕ)5(-0)НА, -М(Н)Б(-О)2НА, -М(Не)5(-0)286, - М-5(-0)(Н52)ВЯ?, --ОВе, -0(0-0)88, -О(С0-О)М(Неа)Ве» -0(0-0)0Н8?, - 5НЯ, -5(-0)88, -5(-0О)М(Н)Н, -5(-0)М(Нг)Ве», -(-О2)Н5, -5(-0)2М( H) Ne, -55-0)2M(Neg)Ve, -5(-0(-M As); where the indicated aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2 or with C- C-alkyl-; or when 2 K" groups are present in the ortho position to each other on an aryl or heteroaryl ring, the indicated 2 K" groups together form a bridge: "О(Снгаг5о "О(СнНаУО), "МН(С(-ОУМН ", where " means the place of attachment of the specified aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, vea(He)M-C1-Cv-Alkyl, HO-C.i-Cv -alkyl, C1-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, C1-Cv-alkenyl-, C2-Cv-alkynyl-, C-7/--len heterocycloalkyl, aryl-, heteroaryl-, -6(-0)H5, -С(-О)М(Н)НА, -С(-О)М(Нба)Бе -0(-0)0-Н5, - М(Вба)Ве», -MO», -ЖЩ(НС(-О)Ве, -М(Нбс)С(-0)Н88, -МЩ(Н)С(-О)М(Аба)Aev, - М(Абг)С(-О)М(Нвба)не", -М(Н)ИС(-О)ОНе, -М(Нес)С(-ОО Не, -М(Н)Б(-0)Н5 . . -O)M(H)H, -5(-0O)M(Bba)BeB, -5(-O2)8H5, -5(-0)2M(H)A5, -5(-0)2M(Nba )ve", -5(-0)(-МНАб)НЯ or /-5(-0)2-(3-7-membered heterocycloalkyl); where 3-7-membered heterocycloalkyl- or heteroaryl is indicated, is optionally substituted, identically or differently, with 1, 2, C or 4 C-Cv-alkyl; t is an integer of 0, 1, 2, 3, 4, 5 or 6; n is an integer of 0, 1, 2, 3, 4 or 5; and

X is chosen from: 5, 5(-0), 5(-0)2, O, MAYE, Svbardvej; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof.

In another preferred embodiment, the invention relates to a compound of the general formula I:

AND

Neon

Fe x M

Fe;

AND

Eat where:

What does d mean? where at 7 4s

And where " indicates the place of attachment of the indicated groups to the molecule; 2 means -С(-О)М(Н)В: or -С(-5М(Н) 2); where " indicates the place of attachment of the indicated groups to the molecule;

B2 means a hydrogen atom, or C.:-Cv-alkyl-; where the specified C:i-Cv-alkyl- is optionally substituted, identically or differently, by 1, 2, C or 4 groups selected from: halogen, OH, -CM, Ci-Cv-alkyl, Ci-Cv- Alkoxy;

BZ means aryl-X or heteroaryl-x-, where the indicated aryl-X or heteroaryl-X is optionally substituted, identically or differently, by 1, 2, 3, 4 or 5 K" groups;

Ba, B, d's, DYA are chosen, independently of each other, from the following: hydrogen, halogen, -CM,

C:-C1-alkyl, C1-C1-alkoxy-, halo-C1-C1-alkyl, halo-C1-C1-alkoxy;

IN? means a hydrogen atom, or Ci-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CnHg )t-(3-7-membered heterocycloalkyl), aryl-Ci-Ci-alkyl, heteroaryl-Ci-Ci-alkyl, halo-Ci-Ci-alkyl, Bba(Beb)M-Ci-Ci-alkyl, HO- S.:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C--Cv-cycloalkenyl-, aryl- or heteroaryl; specified C-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-ene heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kba(Nev)M-C1-Cv-alkyl, HO-C1- C1-Alkyl, -C1-C1-Alkyl-CM, C1-C1-Alkoxy-C1-C1-Alkyl, halo-C1-

C1-Alkoxy-C1-C8-alkyl, C3-C8-cycloalkyl, 3-7-membered heterocycloalkyl, C4-C8-cycloalkenyl-,

aryl- or heteroaryl is optionally substituted, identically or differently, by 1, 2, 3, 4 or 5 KV groups;

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C--

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B' means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bea(Bev)M-Ci-Cv-alkyl, HO- S.: -Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, C2-C8-alkenyl-, C2-C8-alkynyl-, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -b(-0)H6, -C(-O)M(H) Nba, -С(-О3)М(Нба)ВНе, -С(-03)0-Нб, -М(Нба)Бе», -МО», -М(Н)С(-О)Не, -М (Nbs)C(-0)H88, -MSH(H)C(-O)M(Aba)Aev, -M(Abg)C(-O)M(Nvba)ne», -M(H)IS( -О)ОНе, -М(Нес)С(-ООНе, -М(Н)Б(-0)Н5, -М(Нбе)5(-0)НА, -М(Н)Б(-О) 2НЕ, -М(Нег)В(-0)2Нб, -М-5(-0)(Нба)Нб», --ОН, -0(0-0)не, -О(С0-О)М( Hba)Bne, -O(C0-0)OH8, -5285, -5(-0)Hb, -5(-O)M(H)H, -5(-0O)M(Bba)BeB, -5 (-О2)Н8, -5(-0)2М(Н)Не, -5(-0)2М(Нба)Бе», -5(-0)(-МАбе)Бе; where aryl- or heteroaryl is indicated is optionally substituted, identically or differently, by 1, 2 or 3 C-C-alkyl; or when 2 E" groups are present in the ortho position to each other on an aryl or heteroaryl ring, the specified 2 B" groups together form a bridge : "О(Снгаг5о "О(СнНаУО), "МН(С(-ОУМН)", where " means the point of attachment of the indicated aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl,

Vba(de)M-Si-Cv-alkyl, HO-C:-Cv-alkyl, Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, Co-Cv -alkenyl-, С2-Св-alkynyl-, С3-7/--ene heterocycloalkyl, aryl-, heteroaryl-, -б(-0)Н6, -С(-О)М(Н)Нба, -С(- О3)М(Нба)ВНе, -С(-03)0-Нб, -М(Нба)Бе», -МО», -М(Н)С(-О)Не, -М(Нбс)С(- 0)Н88, -МЩ(Н)С(-О)М(Аба)Аев, -М(Абг)С(-О)М(Нвба)не», -М(Н)ИС(-О)ОНе, - M(Nes)C(-OO Ne, -M(H)B(-O)NYA, -M(Nb)5(-0)NYA, -M(H)B(-O)2AYA, -M(Neg )5(-0)286, -М-5(-0)(Н52)ВЯ?, --ОВе, -0(0-0)8e, -Ф(С-О)М(Нба)ВНе, -0 (С0-0)ОН8, -5855, -5(-0)Н88, - 5(-О)М(Н)БЯ, -5(-0)М(Нг)Бе», -(-0)2Н5, -5(-0)2M(H)He, -(-0)2M(Na) Be», -(-OX-M As), -5(-0)2-(3-7-membered heterocycloalkyl ); where the specified 3-7-ene heterocycloalkyl- or heteroaryl is optionally substituted, identically or differently, with 1, 2, C or 4 C-Cv-alkyl-; t means an integer 0, 1, 2, 3, 4, 5, or 6; n is an integer of 0, 1, 2, 3, 4, or 5; and

X is 5, 5(50), 5(50)2, O, MAE or Svbadb,

In another preferred embodiment, the invention relates to a compound of the general formula I:

AND

But. dn /Fe xx M fe;

AND

And where:

What does d mean? where in 7 4c and where " indicates the place of attachment of the specified groups to the molecule; 2 means -С(-О)М(Н)А: or -С(-55М(Н) 2;

Bg means C1-C6-alkyl;

where the indicated C-C-alkyl is optionally substituted, identically or differently, by 1 or 2 groups selected from: halogen, -OH, -CM, C1-C3-alkyl, C-C-- alkoxy;

BZ means aryl-X or heteroaryl-xX-, where the indicated aryl-X or heteroaryl-X is optionally substituted, identically or differently, by 1, 2, 3, 4 or 5 KE" groups;

Ba, B, d's, DYA are chosen, independently of each other, from the following: hydrogen, halogen, -CM,

C:-C1-alkyl, C1-C1-alkoxy-, halo-C1-C1-alkyl, halo-C1-C1-alkoxy;

IN? means a hydrogen atom, or Ci-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CnHg )t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bei)M-C1-Cv-alkyl, HO- S.:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C--Cv-cycloalkenyl-, aryl- or heteroaryl; specified C-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-ene heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kba(Nev)M-C1-Cv-alkyl, HO-C1- C1-Alkyl, -C1-C1-Alkyl-CM, C1-C1-Alkoxy-C1-C1-Alkyl, halo-C1-

C1-Alkoxy-C1-C8-alkyl, C3-C8-cycloalkyl, 3-7-membered heterocycloalkyl, C4-C8-cycloalkenyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2 , Z, 4 or 5 K8 groups;

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C--

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:i-C6-alkyl- or heteroaryl-C:-C6- alkyl-;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kea(Nev)M-C1-Cv-alkyl, HO- C:1-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, C2-C8-alkenyl-, C2-C8-alkynyl-, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -b(-0)H6, -C(-O)M(H) Nba, -С(-О3)М(Нба)ВНе, -С(-03)0-Нб, -М(Нба)Бе», -МО», -М(Н)С(-О)Не, -М (Nbs)C(-0)H88, -MSH(H)C(-O)M(Aba)Aev, -M(Abg)C(-O)M(Nvba)ne», -M(H)IS( -О)ОНе, -М(Нес)С(-ООНе, -М(Н)Б(-О)НА, -М(Нб)5(-0)НА, -М(Н)Б(-О0) 2НЯ, -М(Нег)5(-0)286, -М-5(-0)(Н52)ВЯ?, -ОВе, -0(0-0)88, -О(С0-О)М(Неа )Be" -0(0-0)0Н8?, -5НЯ, -5(-0)88, -5(-0О)М(Н)Н, -5(-0)М(Нг)Бе", - (-O2)H5, -5(-0)2M(H) He, -55-0)2M(Neg)Beh, -5(-0(-M As); where the indicated aryl- or heteroaryl is optional substituted, identically or differently, by m/y 1, 2 or C Ci-Cv alkyls; or when 2 K" groups are present in the ortho position to each other on an aryl or heteroaryl ring, the indicated 2 K" groups together form a bridge: " О(Снг)2»6О" "О(СНгІХ), "МН(С(-О))МН", where 7" means the point of attachment of the specified aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl,

Vba(de)M-Si-Cv-alkyl, HO-C:-Cv-alkyl, Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, Co-Cv -alkenyl-, C2-C1-alkynyl-, C-7/--ene heterocycloalkyl, aryl-, heteroaryl-, -6(-0)Н5, -С(-О)М(Н)НЯ, -С(- О)М(Нба)Бе -0(-0)0-Н5, -М(Вба)Бе», -МО», -ЖШЧ(НС(-О)Бе, -М(Neg)0(-0)8e ,. -Ш(Н)ИС(-ОМ(Ва)ве, -М(Нег)С(-О)М(На)Ве», -Ш(Н)С(-О)ОВе, -М(Не) С(-О)ОВ8, -М(Н)Б(-О)НА, -М(Нб)5(-0)НА, -М(Н)Б(-О0)2НА, -М(Neg)5( -0)286, -М-5(-0)(Н52)ВЯ?, -ОВе, -0(0-0)8е, -Ф(С-О)М(Нба)ВНе, -0(С0-0 )ОН8, -5855, -5(-0)Н88, - 5(-О)М(Н)ВЯ, -5(-0)М(Нг)Ве», -5(-0)285, -5( -0)2М(Н)А5, -5(-0)2М(Нба)ве», -5(-0)(-МНАб)НЯ or /-5(-0)2-(3-7-h- lene heterocycloalkyl); where the specified 3-7--lene heterocycloalkyl- or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyl; t means an integer 0, 1, 2 , 3, 4, 5, or 6; n represents an integer of 0, 1, 2, 3, 4, or 5; and

X is 5, 5(50), 5(50)2, O, MAE or Svbarde»,

In another preferred embodiment, the invention relates to a compound of general formula I:

in?

Neon /Fe x MY

F;

AND

Eat where:

What does d mean? where in 7 d' where " indicates the place of attachment of the specified groups to the molecule; 2 means -С(-О)М(Н)А: or -С(-55М(Н) 2;

Bg2 means a methyl or ethyl; where the specified methyl or ethyl is optionally substituted, identically or differently, by 1 or 2 groups selected from: halogen, -OH, -CM, Ci-C3-Alkoxy;

BZ means aryl-X or heteroaryl-X, where the indicated aryl-X or heteroaryl-X is optionally substituted, identically or differently, by 1, 2, 3, 4 or 5 EC" groups;

Вl, В, дес, ДЯ are selected, independently of each other, from the following: hydrogen, halogen, -СМ, Schi-

C1-alkyl, C1-C1-alkyl, halo-C1-C1-alkyl, halo-C1-C1-alkyl;

IN? means a hydrogen atom, or Ci-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CnHg )t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bei)M-C1-Cv-alkyl, HO- S.:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C--Cv-cycloalkenyl-, aryl- or heteroaryl; specified C-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-ene heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(de»)M-C1-Cv-alkyl, HO-C .1-Cv-alkyl, -C1-Cv-alkyl-CM, Ci-Cv-Alkoxy-C:-Cv-alkyl, halo-C1-

C1-Alkoxy-C1-C8-alkyl, C3-C8-cycloalkyl, 3-7-membered heterocycloalkyl, C4-C8-cycloalkenyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2 , 3, 4 or 5 in K8 groups;

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C--

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kea(Nev)M-C1-Cv-alkyl, HO- C:1-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, C2-C8-alkenyl-, C2-C8-alkynyl-, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -b(-0)H6, -C(-O)M(H) Nba, -С(-О3)М(Нба)ВНе, -С(-03)0-Нб, -М(Нба)Бе», -МО», -М(Н)С(-О)Не, -М (Nbs)C(-0)H88, -MSH(H)C(-O)M(Aba)Aev, -M(Abg)C(-O)M(Nvba)ne», -M(H)IS( -О)ОНе, -М(Нес)С(-ООНе, -М(Н)Б(-О)НА, -М(Нб)5(-0)НА, -М(Н)Б(-О0) 2НЯ, -М(Нег)5(-0)286, -М-5(-0)(Н52)ВЯ?, -ОВе, z5 -0(0-0)88, -О(С-О)М( He)Be, -0(0-0)085, -5НЯ, -5(-0)88, -5(-0О)М(Н)Н, -5(-0)М(Нг)Бе", - (-O2)H5, -5(-0)2M(H) He, -55-0)2M(Neg)Beh, -5(-0(-M As); where the indicated aryl- or heteroaryl is optional substituted, identically or differently, by 1, 2 or C Ci-Cv alkyls; or when 2 EC" groups are present in the ortho position to each other on an aryl or heteroaryl ring, the indicated 2 K" groups together form a bridge: "O(Sngag5o "О(СнНаУО", "МН(С(-ОУМН)", where " means the point of attachment of the specified aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl,

Vba(de)M-Si-Cv-alkyl, HO-C:-Cv-alkyl, Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, Co-Cv -alkenyl-, C2-C1-alkynyl-, C-7/--ene heterocycloalkyl, aryl-, heteroaryl-, -6(-0)Н5, -С(-О)М(Н)НЯ, -С(- О)М(Нба)Бе -0(-0)0-Н5, -М(Вба)Бе», -МО», -ЖШЧ(НС(-О)Бе, -М(Neg)0(-0)8e ,. -Ш(Н)ИС(-ОМ(Ва)ве, -М(Нег)С(-О)М(На)Ве», -Ш(Н)С(-О)ОВе, -М(Не) С(-О)ОВ8, -М(Н)Б(-О)НА, -М(Нб)5(-0)НА, -М(Н)Б(-О0)2НА, -М(Neg)5( -0)286, -М-5(-0)(Н52)ВЯ?, -ОВе, -0(0-0)8е, -Ф(С-О)М(Нба)ВНе, -0(С0-0 )ОН8, -5855, -5(-0)Н88, - 5(-О)М(Н)ВЯ, -5(-0)М(Нг)Ве», -(-0)2Н5, -5(- 0)2M(H)He, -(-0)2M(Na) Be", -(-OX-M As), -5(-0)2-(3-7-membered heterocycloalkyl); where indicated 3-7-ene heterocycloalkyl- or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 C-Cv-alkyl; t means an integer 0, 1, 2, 3, 4, 5 or 6; n is an integer of 0, 1, 2, 3, 4 or 5; and

X is 5, 5(50), 5(50)2, O, MAE or Svbadb,

In another preferred embodiment, the invention relates to a compound of the general formula I:

AND

NN

/Fe

CHIH,

F,

AND

Eat where:

What does d mean? where in 7 4c and where " indicates the place of attachment of the specified groups to the molecule; 2 means -С(-О)М(Н)В: or -С(-5М(Н) 2;

B2 means C:-Ca-alkyl; where the specified Ci-C.a-alkyl- is optionally substituted, identically or differently, by 1 or 2 groups selected from: halogen, OH, -CM, C1-C3-alkyl, C--C4- alkoxy;

BZ means aryl-X or heteroaryl-X; where the indicated aryl-X or heteroaryl-X is optionally substituted, identically or differently, by 1 or 2 B" groups;

Ва, ВД, Де, ДЯ are selected, independently of each other, from the following: hydrogen, halogen, -СМ, С1-

C1-alkyl, C1-C1-alkyl, halo-C1-C1-alkyl, halo-C1-C1-alkyl;

AV? means a hydrogen atom, or Ci-Cv-alkyl, -(CHn)n-C2-Cn-alkenyl, -(CHn)p-C2-Cn-alkynyl, -(CHn)t-C3-Cn-cycloalkyl, -(CnHg )t-(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(Bei)M-C1-Cv-alkyl, HO- S.:-Cv-alkyl, -C1-Cv-alkyl-CM,

Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-Ci-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl, C--Cv-cycloalkenyl-, aryl- or heteroaryl; specified C-Cv-alkyl, -(CHg)p-C2-Cv-alkenyl, -(CHg)p-C2-Cv-alkynyl, -(CHg)t-C3-Cv-cycloalkyl, -(CHg)t- (3-7-ene heterocycloalkyl), aryl-C1-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bba(de»)M-C1-Cv-alkyl, HO-C .1-Cv-alkyl, -C1-Cv-alkyl-CM, Ci-Cv-Alkoxy-C:-Cv-alkyl, halo-C1-

C1-Alkoxy-C1-C8-alkyl, C3-C8-cycloalkyl, 3-7-membered heterocycloalkyl, C4-C8-cycloalkenyl-, aryl- or heteroaryl is optionally substituted, identically or differently, 1, 2 , 3, 4 or 5 KV groups;

Ve, Vba, dDBB, Des mean, independently of each other, a hydrogen atom, or Ci-Cv-alkyl, HO-C-

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kea(Nev)M-C1-Cv-alkyl, HO- C:1-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, C2-C8-alkenyl-, C2-C8-alkynyl-, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -6(-0)Н5, -С(-О)М(Н) НА, -С(-О)М(Нба)Бе -0(-0)0-Н5, -М(Вба)Бе», -МО», -ЖХЧ(НС(-О)Бе, -М(Neg) 0(-0)8e,. -Ш(Н)ИС(-ОМ(Ва)ве, -М(Нег)С(-О)М(На)Ве», -Ш(Н)С(-О)ОВе , -М(Не)С(-О)ОВ8, -М(Н)Б(-О)НА, -М(Нб)5(-0)НА, -М(Н)Б(-О0)2НА, - М(Neg)5(-0)286, -М-5(-0)(Н52)ВЯ?, -ОВе, -0(0-0)88, -О(С0-О)М(Неа)Ве» -0(0-0)0Н8?, -5НЯ, -5(-0)88, -5(-0О)М(Н)Н, -5(-0)М(Нг)Ве», -(-О2 )H5, -5(-0)2M(H) He, -55-0)2M(Neg)Bei, -5(-0(-M As); where the indicated aryl- or heteroaryl is optionally substituted, identical or differently, 1, 2 or C C-Cv alkyls; or when 2 K" groups are present in the ortho position to each other on an aryl or heteroaryl ring, the specified 2 K" groups together form a bridge: "O(Sngag5o "O( СнНаУО", "МН(С(-ОУМН)", where " means the point of attachment of the indicated aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-Alkoxy-, Ci-Cv-Alkyl, halo-C1-Cv-Alkyl, vea(He)M-C1-Cv-Alkyl, HO-C.i-Cv -alkyl, C1-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, C1-Cv-alkenyl-, C2-Cv-alkynyl-, C-7/--len heterocycloalkyl, aryl-, heteroaryl-, -6(-0)H5, -С(-О)М(Н)НА, -С(-О)М(Нба)Бе -0(-0)0-Н5, - М(Вба)Ве», -МО», -ЖХ(НС(-О)Ве, -М(Нег)0(-0)8е, -Х(Н)ИС(-ОМ(Ва)ве, -М (Neg)С(-О)М(На)Ве», -Ш(Н)С(-О)ОВе, -М(Не)С(-О)ОВ8, -М(Н)Б(-0)Н5 . , --ОН, -0(0-0)не, -О(С-О)М(Нба)Бе», -0(С0-0)ОНе, -586, -5(-0)Н8, - 5 (-OM(H)He, -5(-0O)M(Vba) Be», -5(-0)2H, -(-0)2M(H)He, -5(-0)2M(Nea) Ве", -(-О3Х-МАс), -5(-0)2-(3-7-membered heterocycloalkyl); where the specified 3-7-membered heterocycloalkyl- or heteroaryl is optionally substituted, identical or different, 1, 2, C or 4 C-Cv-alkyl-; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5; and

X is 5, 5(50), 5(50)2, O, MAE or Svbarde»,

In another preferred embodiment, the invention relates to a compound of the general formula I:

AND

Neon

Fe x M

J

AND

And where:

What does d mean? where in 7 4c and where " indicates the place of attachment of the indicated groups to the molecule; 2 means -С(-О)М(Н)В:2 or -С(-5)М(Н)В;

B2 means a C.-Ca-alkyl-; where the indicated Ci-C.a-alkyl- is optionally substituted, identically or differently, by 1 or 2 groups selected from: halogen, -OH, -CM, C1-C3-alkyl, Ci-C-- alkoxy;

BZ is selected from the following: aryl-X or heteroaryl-X; where the specified aryl-X or heteroaryl-X is optionally substituted, identically or differently, by 1 or 2 KE" groups;

Ba, BA, de, ДЯ are chosen, independently of each other, from the following: hydrogen, halogen, -СМ,

C:-C1-alkyl, C1-C1-alkoxy-, halo-C1-C1-alkyl- or halo-C1-C1-alkoxy;

AV? means a hydrogen atom, C1-C6-alkyl, -(CNeg)t-(3-7-ene heterocycloalkyl), aryl- or heteroaryl; where the indicated C1-C8-alkyl, -(CH8)t-(3-7-membered heterocycloalkyl), aryl- or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 8 groups;

VU, ba, where. des mean, independently of each other, a hydrogen atom, or C1-Cv-alkyl, HO-C--

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Kea(Nev)M-C1-Cv-alkyl, HO- C:1-Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, C2-C8-alkenyl-, C2-C8-alkynyl-, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -b(-0)H6, -C(-O)M(H) Nba, -С(-О3)М(Нба)ВНе, -С(-03)0-Нб, -М(Нба)Бе», -МО», -М(Н)С(-О)Не, -М (Nbs)C(-0)H88, -MSH(H)C(-O)M(Aba)Aev, -M(Abg)C(-O)M(Nvba)ne», -M(H)IS( -О)ОНе, -М(Нес)С(-ООНе, -М(Н)Б(-0)Н5, -М(Нбе)5(-0)НА, -М(Н)Б(-О) 2НЕ, -М(Нег)Б(-0)2Нб, -М-5(-0)(Нба)Нб», --ОН, -0(0-0)88, -О(С0-О)М( Nea)Be» -0(0-0)0Н8?, -5НЯ, -5(-0)88, -5(-0О)М(Н)Н, -5(-0)М(Нг)Бе» -(-O2)H5, -5(-0)2M(H) He, -55-0)2M(Neg)Beh, -5(-0(-M As); where the indicated aryl- or heteroaryl is optional necessarily substituted, identically or differently, by 1, 2 or C Ci-Cv alkyls; or when 2 K" groups are present in the ortho position to each other on an aryl or heteroaryl ring, the specified 2 K" groups together form a bridge: "O( Снгаг5о "О(СнНаУО", "МН(С(-ОУМН)", where " means the point of attachment of the specified aryl or heteroaryl ring;

IN? means hydrogen or a halogen atom, or -CM, C1-Cv-alkyl, C1-Cv-alkyl, halo-C1-Cv-alkyl,

Vba(de)M-Si-Cv-alkyl, HO-C:-Cv-alkyl, Ci-Cv-Alkoxy-Ci-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-Cv-Alkyl, Co-Cv -alkenyl-, C2-C1-alkynyl-, C-7/--ene heterocycloalkyl, aryl-, heteroaryl-, -6(-0)Н5, -С(-О)М(Н)НЯ, -С(- О)М(Нба)Бе -0(-0)0-Н5, -М(Вба)Бе», -МО», -ЖШЧ(НС(-О)Бе, -М(Neg)0(-0)8e ,. -Ш(Н)ИС(-ОМ(Ва)ве, -М(Нег)С(-О)М(На)Ве», -Ш(Н)С(-О)ОВе, -М(Не) С(-О)ОВ8, -М(Н)Б(-О)НА, -М(Нб)5(-0)НА, -М(Н)Б(-О0)2НА, -М(Neg)5( -0)286, -М-5(-0)(Н52)ВЯ?, -ОВе, 0) -0(0-0)8e, -Ф(С-О)М(Нба)ВНе, -0(С0 -0)ОН8, -5855, -5(-0)Н88, - 5(-О)М(Н)ВЯ, -5(-0)М(Нг)Ве», -(-0)2Н5, -5 (-0)2M(H)He, -(-0)2M(Na) Be», -(-OX-M As), -5(-0)2-(3-7-membered heterocycloalkyl); where the specified 3-7-membered heterocycloalkyl- or heteroaryl is optionally substituted, identically or differently, with 1, 2, C or 4 C-Cv-alkyl-; t means an integer 0, 1, 2, 3, 4, 5 or 6; n represents an integer of 0, 1, 2, 3, 4, or 5; and

X is 5, 5(50), 5(50)2, O, MAE or Svbadb,

In another preferred embodiment, the invention relates to a compound of the general formula I:

AND

On N /Fe x M fe;

AND

And where:

What does d mean? where in 7 d' where " indicates the place of attachment of the indicated groups to the molecule; because

2 means -С(-О)М(Н)А: or -С(-55М(Н) 2;

Bg means a C:-C1-alkyl-; where the indicated C-C.a-alkyl- is optionally substituted, identically or differently, by 1 or 2 groups selected from: halogen, OH, -CM, C1-C3-alkyl, C-C4- alkoxy;

BZ means aryl-X or heteroaryl-X; where the indicated aryl-X or heteroaryl-X is optionally substituted, identically or differently, by 1 or 2 B" groups;

Ba, B, d's, DYA are chosen, independently of each other, from the following: hydrogen, halogen, -CM,

C:-C1-alkyl, C1-C1-alkoxy-, halo-C1-C1-alkyl, halo-C1-C1-alkoxy;

AV? means a hydrogen atom, C:1-C6-alkyl, -(CNeg)t-(3-7-ene heterocycloalkyl), aryl- or heteroaryl; where the indicated C1-C8-alkyl, -(CH8)t-(3-7-membered heterocycloalkyl), aryl- or heteroaryl is optionally substituted, identically or differently, by 1, 2, C or 4 8 groups;

Ve, Vba, dDBB, Des mean, independently of each other, a hydrogen atom, or Ci-Cv-alkyl, HO-C-

C1-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl-, 3-7-membered heterocycloalkyl, aryl-, heteroaryl-, aryl-C:-C6-alkyl- or heteroaryl-C:-C6-alkyl -;

B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halo-C1-Cv-alkyl, Bea(Bev)M-Ci-Cv-alkyl, HO- S.: -Cv-alkyl, C1-Cv-Alkoxy-C1-Cv-Alkyl, halo-C1-Cv-Alkoxy-C1-

C1-alkyl, C2-C8-alkenyl-, C2-C8-alkynyl-, 3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -6(-0)Н5, -С(-О)М(Н) НЯ, -С(-О)М(Нба)Ве, -0(-0)0-Н8, -М(Вба)Ве», -МО», -ЖХХ(Н)С(-О)Ве, -М (Nbs)C(-0)H88, -MSH(H)C(-O)M(Aba)Aev, -M(Abg)C(-O)M(Nvba)ne», -M(H)IS( -О)ОНе, -М(Нес)С(-ООНе, -М(Н)Б(-0)Н5, -М(Нбе)5(-0)НА, -М(Н)Б(-О) 2НЕ, -М(Нег)В(-0)2Нб, -М-5(-0)(Нба)Нб», --ОН, -0(0-0)не, -О(С0-О)М( Hba)Bne, -O(C0-0)OH8, -5285, -5(-0)Hb, -5(-O)M(H)H, -5(-0O)M(Bba)BeB, -5 (-O2)He, -5(-0)2M(H)He, -55-0)2M(Nea)He, -5(-0-M Ac)He; where the indicated aryl- or heteroaryl is optionally substituted, identically or differently, by 1, 2 or C C-Cv alkyls; or when 2 E" groups are present in the ortho position to each other on an aryl or heteroaryl ring, the indicated 2 B" groups together form a bridge: зо "О(Снгаг5о "О(СнНаУО), "МН(С(-ОУМН)", where " means the point of attachment of the indicated aryl or heteroaryl ring;

BB means a halogen atom, and -СМ, -М(Нба)Бе» or -ОНеЕ; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5; and

X is 5, 5(-0), 5(-0)2, O, MAE or Stbardv,

It is to be understood that the present invention relates to any sub-combination of any embodiment or aspect of the present invention of the compound of general formula II, above.

More particularly, the present invention includes compounds of general formula !, described in the experimental section of this specification, below.

The compounds of the present invention may have one or more asymmetric centers, depending on the location and nature of the various desired substituents. Asymmetric carbon atoms can be present in the (K) or (5) configuration, resulting in a racemic mixture, in the case of one asymmetric center, and a diastereomeric mixture, in the case of several asymmetric centers. In a certain case, asymmetry may occur due to limited rotation about a certain bond, for example, a central bond connecting two substituted aromatic rings of the above compounds.

Ring substituents can also be in cis or trans form. All such configurations (including enantiomers and diastereomers) are included within the scope of this invention.

Compounds exhibiting the most desirable biological activity are preferred. Isolated, pure or partially purified isomers and stereoisomers or racemic or diastereomeric mixtures of the compounds of the present invention are also included in the scope of this invention. Cleaning and selection of such materials is carried out according to standard technologies known in the industry.

Optical isomers are obtained by redissolving the racemic mixture according to standard techniques, for example, by forming diastereoisomeric salts using an optically active acid or base, or by forming covalent diastereomers. Examples of suitable acids include: tartaric, diacetyltartaric, ditoluenetartaric and camphorsulfonic acid. Mixtures of diastereomers can be separated into individual diastereomers based on their physical and/or chemical differences by methods known in the art, such as chromatography or fractional crystallization. Optically active bases or (610) acids are then released from the individual diastereomeric salts. Another way to separate optical isomers involves the use of chiral chromatography (eg, chiral HPLC columns), with or without standard derivatization, optimally selected for maximum separation of enantiomers. Suitable chiral HPLC columns are, among others, manufactured by Oiaceae, for example, SpigaseI OO and Spigasei! 03), all are selected in working order. Enzymatic resolution, with or without derivatization, is also suitable. Optically active compounds of the present invention can also be obtained by chiral synthesis using optically active starting materials.

In order to separate different types of isomers from each other, use the rules of ISHRAS section E (Riege Arri Spet 45, 11-30, 1976).

The present invention includes all possible stereoisomers of the compounds of the present invention as individual stereoisomers or as any mixture of specified stereoisomers, in any ratio.

Isolation of a single stereoisomer, for example, a single enantiomer or a single diastereomer, of the compounds of this invention is carried out by any method known in the field, such as chromatography, especially chiral chromatography.

Also, the compounds of this invention may exist as tautomers. For example, any compound of the present invention that contains a pyrazole residue as a heteroaryl, for example, can exist as a 1H tautomer or a 2H tautomer, or even a mixture of any number of two tautomers, or a triazole residue, for example, can exist as a 1H tautomer, a 2H tautomer , or the 4H tautomer or even a mixture of any number of the specified 1H, 2H and 4H tautomers, in particular:

H nm w- -5 "nn -y h

I ! in her

N

ZN-tautomer 2H-tautomer ZN-tautomer

The present invention includes all possible tautomers of the compounds of the present invention as individual tautomers or as any mixture of said tautomers, in any ratio.

Also, the compounds of this invention can exist as M-oxides, which are characterized by the fact that at least one nitrogen of the compounds of this invention is oxidized. The present invention includes all such possible M-oxides.

Moreover, the present invention includes all possible crystalline forms or polymorphs of the compounds of the present invention, as individual polymorphs or as a mixture of more than one polymorph, in any ratio.

The compounds of this invention can exist as a hydrate or solvate, where the compounds of this invention contain polar solvents, in particular water, methanol or ethanol, for example, as a structural element of the crystal lattice of the compounds. The amount of polar solvents, in particular water, can be in a stoichiometric or non-stoichiometric ratio. In the case of stoichiometric solvates, possible are, for example, hydrates, hemi-, (semi-), mono-, hemi-, di-, tri-, tetra-, penta-, etc. solvates or hydrates, respectively. The present invention includes all such hydrates or solvates.

In an embodiment of the above aspects, the invention relates to a compound of formula I, according to any of the above embodiments, in the form of a stereoisomer, tautomer, M-oxide, hydrate, solvate, or its salt, or a mixture thereof.

The compounds of this invention have unexpectedly shown the ability to inhibit Mr5-1 kinase and therefore can be used to treat or prevent diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses or inappropriate cellular inflammatory responses or diseases mediated by uncontrolled cell growth, proliferation and/or survival. or survival, inappropriate cellular immune responses, or inappropriate cellular inflammatory responses, particularly where uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, or inappropriate cellular inflammatory responses are mediated by Mp5-1 kinase, such as, for example, hematologic tumors, solid tumors and/or their metastases, for example, leukemia and myelodysplastic syndrome, malignant lymphomas, head and neck tumors, including brain tumors and brain metastases, thoracic tumors, including non-small cell and small cell lung cancer, gastrointestinal tumors, endocrine tumors, breast tumors and other gynecological tumors, urological tumors, including kidney, bladder and prostate tumors, skin tumors and sarcomas, and/or their metastases.

Therefore, compounds of formula I, above, are valuable as therapeutic agents.

Accordingly, in another embodiment, the present invention relates to a compound of general formula I, above, or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or its salt, in particular, its pharmaceutically acceptable salt, or a mixture thereof, for use in treatment or disease prevention.

In another embodiment, the present invention relates to a method of treating disorders associated with accelerated uncontrolled cell proliferative processes in a patient in need thereof, which comprises administering to the patient an effective amount of a compound of formula I.

The term "treatment" as used herein is used generically, for example, the care or treatment of a patient for the purpose of combating, alleviating, reducing, attenuating, ameliorating a disease or disorder such as carcinoma.

The terms "subject" or "patient" include organisms suffering from a cell proliferative disorder or who may otherwise benefit from administration of a compound of the invention, such as humans and non-human animals. Preferred individuals include human patients suffering from or prone to suffering from a disorder of cell proliferation or related conditions as described herein. The term "non-human animals" includes vertebrates such as mammals such as non-human primates, sheep, cows, dogs, cats and rodents such as mice and non-mammalians such as chickens, amphibians, reptiles, etc.

The terms "disorder of cell proliferation" or "disorder associated with accelerated uncontrolled cell proliferative processes" include disorders mediated by unwanted or uncontrolled cell proliferation. The compounds of this invention are used to prevent, inhibit, block, reduce, reduce, control, etc., cell proliferation and/or cell division, and/or induce apoptosis.

This method includes administering to a subject in need thereof, including a mammal, including a human, an amount of a compound of the present invention, or a pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate, or solvate thereof, that is effective in treating or preventing a disorder.

In another embodiment, the present invention relates to a compound of the general formula I, or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or its salt, in particular, its pharmaceutically acceptable salt, or a mixture thereof, for use in the treatment or prevention of a disease, where the specified disease means a disease of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune response or inappropriate cellular inflammatory response, in particular, where uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune response or inappropriate cellular inflammatory response are mediated by myogen- activated protein kinase (MEK-ECK) pathway, more particularly where a disease of uncontrolled cell growth, proliferation and/or survival, an inappropriate cellular immune response or an inappropriate cellular inflammatory response means hematological tumor, solid tumor and/or their metastases, for example leukemia and myelodysplastic syndrome, malignant and lymphomas, head and neck tumors, including brain tumors and brain metastases, thoracic tumors, including non-small cell and small cell lung cancer, gastrointestinal tumors, endocrine tumors, breast tumors and other gynecological tumors, urological tumors, including kidney tumors , bladder and prostate, skin tumors and sarcomas, and/or their metastases.

The present invention also relates to suitable forms of the compound of the invention as described herein, such as metabolites, hydrates, solvates, prodrugs, salts, in particular pharmaceutically acceptable salts, capable of hydrolyzing ip mimo esters and co-precipitation.

The term "pharmaceutically acceptable salt" refers to a relatively non-toxic, inorganic or organic acid addition salt of a compound of this invention. For example, see 5. M. Vegde, ей а). "Rpagtaseshisa! Zanv, 7" U. Rpagt. 5 1977, 66, 1-19.

Suitable pharmaceutically acceptable salts of compounds of this invention may include, for example, acid addition salts of compounds of this invention containing a chain or ring nitrogen atom, for example, which are sufficiently basic, such as acid addition salts of inorganic acids such as, for example, hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric, bisulfuric, phosphoric or nitric acid, or organic acids such as formic, acetic, acetoacetic, pyruvic, trifluoroacetic, propionic, oleic, hexanoic, heptanoic, undecanoic, lauric, benzoic, salicylic, 2 -(4-hydroxybenzoyl)-benzoic, camphoric, cinnamic, cyclopentanepropionic, digluconic, 3-hydroxy-2-naphthoic, nicotinic, pamoic, pectinic, persulphuric, 3-phenylpropionic, picric, pivalic, 2-hydroxyethanesulfonate, itaconic, sulfamic, trifluoromethanesulfonic , dodecylsulfonic, ethanesulfonic, benzenesulfonic, para-toluenesulfonic, methanesulfonic, 2-naphthalenesulfonic, (610) naphthalenedylsulfonic, camphorsul phonic acid, citric acid, tartaric acid, stearic acid, lactic acid,

oxalic, malonic, amber, malic, adipic, alginic, maleic, fumaric,

UO-gluconic, mandelic, ascorbic, glucoheptanoic, glycerophosphoric, aspartic, sulfosalicylic, hemisulfuric or thiocyanic acid.

Also, other suitable pharmaceutically acceptable salts of the compounds of the present invention which are essentially acidic are alkali metal salts, for example sodium or potassium salts, alkaline earth metal salts, for example calcium or magnesium salts, ammonium salts, or organic base salts which will carry a physiologically acceptable cation, for example, a salt of M-methyl-glucamine, dimethyl-glucamine, ethyl-glucamine, lysine, dicyclohexylamine, 1,6-hexadiamine, ethanolamine, glucosamine, sarcosine, serinol, tris-hydroxy-methyl-aminomethane, aminopropanediol, sovak base, 1-amino-2,3,4-butanetriol. In addition, basic nitrogen-containing groups can be quaternized by agents such as lower alkyl halides such as methyl, ethyl, propyl and butyl chlorides, bromides and iodides; dialkyl sulfates such as dimethyl, diethyl, and dibutyl sulfate; and diamyl sulfates, long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides, aralkyl halides such as benzyl and phenethyl bromides, and the like.

Those skilled in the art will appreciate that acid addition salts of the claimed compounds can be prepared by reacting the compound with an appropriate inorganic or organic acid, by any of the known methods. Alternatively, the alkali and alkaline earth metal salts of the acid compounds of the invention were prepared by reacting the compounds of the invention with a suitable base by any of the known methods.

The present invention includes all possible salts of the compounds of the present invention as individual salts or as any mixture of these salts, in any ratio.

As used herein, the term "ip mimo hydrolyzable ester" means an i p mimo hydrolyzable ester of a compound of the present invention that contains a carboxy or hydroxy group, e.g., a pharmaceutically acceptable ester that hydrolyzes in the human or animal body to the parent acid or alcohol. Suitable pharmaceutically acceptable esters for the carboxy group include, for example, alkyl, cycloalkyl, and optionally substituted phenylalkyl, in particular, benzyl esters, C:1-C6-alkoxymethyl esters, for example, methoxymethyl, C1-C6-alkanoyloxymethyl esters, for example, pivaloyloxymethyl, phthalidyl esters, C3-C8-cycloalkyloxy-carbonyloxy-C1-C8-alkyl esters, for example, 1-cyclohexylcarbonyloxyethyl; 1,3-dioxolen-2-onyl methyl esters, e.g.

B-methyl-1,3-dioxolen-2-onylmethyl; and C 1 -C 2 -Alkoxycarbonyloxyethyl esters, for example, 1-methoxycarbonyloxyethyl, and can be formed with any carboxy group of the compound of the present invention.

Hydrolyzable ip mimo esters of compounds of the present invention that contain a hydroxy group include inorganic esters such as phosphate esters and (alpha)-acyloxyalkyl ethers and related compounds which, upon hydrolysis of the ip mimo ester, decompose to yield the parent hydroxy group. Examples (alpha|-Azuioxyalkyl ethers include acetoxymethoxy and 2,2-dimethylpropionyloxymethoxy. Choice of ester-forming groups hydrolyzable and immo for hydroxy include alkanoyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl, alkoxycarbonyl (yielding alkyl carbonate esters), dialkylcarbamoyl and

M-(dialkylaminoethyl)-M-alkylcarbamoyl (yielding carbamates), dialkylaminoacetyl and carboxyacetyl. The present invention includes all such esters.

Compounds of formula I may be administered as a single pharmaceutical agent or in combination with one or more additional pharmaceutical agents where the combination does not cause unacceptable side effects. Such combination therapy includes administration of a separate pharmaceutical dosage form containing a compound of formula I and one or more additional therapeutic agents, and administration of a compound of formula I and each additional therapeutic agent in its own separate pharmaceutical dosage form. For example, a compound of formula I and a therapeutic agent may be administered to a patient together in a single oral dosage form, such as a tablet or capsule, or each agent may be administered in a separate dosage form.

When using separate dosage forms, the compound of formula I and one or more additional therapeutic agents can be administered substantially simultaneously (eg, in parallel) or separately in a stepwise manner (eg, sequentially).

In another aspect, the invention relates to a pharmaceutical composition comprising a compound of general formula I, or a stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, in particular, a pharmaceutically acceptable salt thereof, or a mixture thereof, and a pharmaceutically acceptable solvent or carrier .

Preferably, the pharmaceutical combination contains:

- one or more compounds of the general formula I, or a stereoisomer, tautomer, M-oxide, hydrate, solvate, or its salt, in particular, its pharmaceutically acceptable salt, or their mixture; and - one or more agents selected from the following: a taxane such as Docetaxel, Paclitaxel or Taxol; an epothilone such as Ixabepilon, Patupilon or Sagopilon; Mitoxantrone;

Prednisolone; Dexamethasone; Estramustine; Vinblastine; Vincristine; Doxorubicin; Adriamycin;

Idarubicin; Daunorubicin; Bleomycin; Etoposide; Cyclophosphamide; Ifosfamide; Procarbazine;

Melphalan; 5-Fluorouracil; Capecitabine; Fludarabine; Cytarabine; Aha-S; 2-Chlor-2-deoxyadenosine; Thioguanine; an anti-androgen such as Flutamide, Cyproterone Acetate or

Bicalutamide; Bortezomib; a platinum derivative such as Cisplatin or Carboplatin; Chlorambucil; Methotrexate; and Rituximab.

In another aspect, the invention relates to a method of preparing a pharmaceutical composition. The method includes the stage of mixing at least one compound of formula I, defined above, with at least one pharmaceutically acceptable carrier, and forming the resulting combination into a suitable form for administration.

In another aspect, the invention relates to the use of a compound of formula Y as defined above for the preparation of a pharmaceutical composition for the treatment or prevention of cell proliferation disorders. In certain embodiments, the cell proliferation disorder is cancer.

The active component of formula I can act systemically and/or locally. For this purpose, it can be administered in a suitable manner, for example orally, parenterally, pulmonaryly, nasally, sublingually, lingually, buccally, rectally, transdermally, conjunctivally, in the ear or as an implant or stent.

When the compounds of the present invention are administered as medicaments to humans and animals, they may be administered as such or as a pharmaceutical composition containing, for example, 0.1-99.5 95 (more preferably, 0.5-90 95) of the active ingredient in combinations with a pharmaceutically acceptable carrier.

Regardless of the chosen route of administration, the compounds of the invention, which are used in a suitable hydrated form, and/or the pharmaceutical compositions of this invention, are formed into pharmaceutically suitable dosage forms by methods known to those skilled in the art.

The actual dosages and timing of administration of the active ingredients of the pharmaceutical compositions of the invention may vary, to obtain an amount of the active ingredient effective to achieve the desired therapeutic response for a particular patient, a composition and a route of administration that are not toxic to the patient.

According to another aspect, the present invention includes methods of preparing a compound of the present invention.

According to the first embodiment, the present invention relates to a method of obtaining a compound of the general formula I, above, where the indicated method includes the stage of interaction of an intermediate compound of the general formula IM: in?

AND

N t i

Z LF in M

AND

IM where A and KE? are as defined for the general formula I above and KZ means a leaving group; with a compound of the general formula Ma:

VZ-U

IMa where EZ is as defined for the general formula I above and Y represents a substituent substituted in the condensation reaction, such as a hydrogen atom, or boronic acid, or boronic ester, for example; thus obtaining a compound of the general formula I:

you

And not 2 Mn /Fe x M in M -f

AND

And where A, EKZ and KE: are as defined for the general formula Y, above.

According to the second embodiment, the present invention also relates to the method of obtaining 5 of the compound of the general formula I, above, where the specified method includes the stage of interaction of the intermediate compound of the general formula Ia: 5

AND

And not 2 MN

Fe xx y

WITH

In M

AND

Ia where EZ and KE are as defined for the general formula Y, above; and A" means d. in"? in" 7 d' de" means the point of attachment of the specified group to the molecule; la, Db, Die and QA are as defined for the general formula I, above and 2" means a group selected from: -F(-О0OH, -С(-5)0OH, -С(-0)0-(С1 -Cv-alkyl) or -C(-5)0O-(C1-Cv-alkyl); with a compound of the general formula IB:

NM

And where is V? is as defined for the general formula I, above, thus obtaining, upon optional deprotection, a compound of the general formula I: 5 in

And not 2 MN /Fe x M in M -f

A where KZ, B" and A are as defined for the general formula Y, above.

According to the second, third embodiment, the present invention also relates to a method for preparing a compound of the general formula I, above, where the specified method includes the stage of interaction of an intermediate compound of the general formula II:

MN se - J

With ra , in M 2 at 5 I! where ECZ and EE are as defined for general formula I above and 02 represents a leaving group, preferably 02 represents a halogen atom; with a compound of the general formula Pa:

A-U

Pa where A is as indicated for the general formula Y above and Y represents a substituent substituted in the condensation reaction, such as boronic acid or a boronic acid ester, for example, thereby obtaining, upon optional deprotection, a compound of the general formula I: 5 c

Neon /Ffe x MY

WITH

In M -f

AND

Where is RU, V? and A are as defined for general formula I, above.

According to the fourth version of the embodiment, it also refers to the method of obtaining the compound of the general formula I, above, where the specified method includes the stage of interaction of the intermediate compound of the general formula MI: 1 o y -M ra Y v M

AND

MI where EZ and A are as defined for the general formula I above and 0! means a leaving group, for example a halogen atom, with a compound of the general formula Ma:

V8ZASNo-MN»g

MPa, where is E? is as indicated for the general formula Y, above, thus obtaining, upon optional deprotection, a compound of the general formula I:

in

Neon /Fe x M

WITH

In M -f

AND

Y where KZ, B" and A are as defined for the general formula Y, above.

According to the fifth version of the embodiment, it also refers to the method of obtaining the compound of the general formula I, above, where the indicated method includes the stage of interaction of the intermediate compound of the general formula MII: 1 o se ho OM Y

From r

In M -f

AND

MI where KZ and A are as defined for the general formula I above and 0 means an optionally protected MNe group with a compound of the general formula MIV:

Oo-SnNA"

Me) where is E? is as indicated for the general formula Y, above, thus obtaining, upon optional deprotection, the compound of the general formula I: 5 v m /fya I x Y

WITH

In M -f

AND

Y where KZ, B" and A are as defined for the general formula Y, above.

According to a further aspect, the present invention includes intermediate compounds suitable for the preparation of compounds of the present invention of general formula I, in particular, in the method described herein.

In particular, this invention includes intermediate compounds of the general formula Ia:

AND

And not 2 MN dk - M prah lf

And M

AND

Ia where EZ and KE are as defined for the general formula Y, above; and A" means d. in"? vya 7 4c 5 v where " means the point of attachment of the specified group to the molecule; la, Db, Die and QA are as defined for the general formula I, above and 2" means a group selected from: -Ф(-О0ОН, - C(-5)0OH, -C(-0)0-(C1-Cv-alkyl) or -C(-5)0O-(C1-Cv-alkyl).

According to another aspect, the present invention includes the use of intermediate compounds of the general formula Ia: 5

AND

And not 2 MN dk -k

ZA boif in M

AND

Ia where EZ and KE are as defined for the general formula Y, above; and A" means d. in"? vya 7 4c where 7" means the point of attachment of the specified group to the molecule; Ka, B", Die and KYA are as defined for the general formula I, above and 2" means a group selected from: -Ф(-ОООН, -C(-5)0OH, -C(-0)0-(C1-Cv-alkyl) or -C(-5)0O-(C1-Cv-alkyl) to obtain a compound of the general formula I as defined above.

According to another aspect, the present invention includes the use of intermediate compounds of the general formula II:

in

MN and - in M 2 o

AND! where ECZ and EE are as defined for general formula I above and 02 represents a leaving group, preferably 02 represents a halogen atom. 5 According to another aspect, the present invention includes the use of intermediate compounds of the general formula II: 5 in

МН and -М with мф in М 2 o

AND! where ECZ and EE are as defined for general formula I above and 02 represents a leaving group, preferably 02 represents a halogen atom; to obtain a compound of general formula I as defined above.

According to another aspect, the present invention includes intermediate compounds of the general formula IM: 5 vi ! not - 7 tMn and d- M "Ai in M

AND

IM where A and KE? are as defined for the general formula I above and KZ means a leaving group.

According to another aspect, the present invention includes the use of intermediate compounds of the general formula IM:

in

And not 2 MN paradise d- M

And M in M

AND

IM where A and K? are as defined for general formula I above and KU represents a leaving group to give a compound of general formula I as defined above. 5 According to a further aspect, the present invention includes intermediate compounds of the general formula

MI: 1 o rai -- M ra Y v M

AND

MI where A and KZ are as defined for the general formula I above and 0 means an optionally protected MNe group or leaving group.

According to another aspect, the present invention includes the use of intermediate compounds of the general formula MI: 1 o y -M ra Y v M

AND

MI where A and KZ are as defined for the general formula I above and 0 means an optionally protected MNe group or leaving group; to obtain a compound of general formula I as defined above.

Experimental section

The following Table provides a list of abbreviations used in this paragraph and in the examples section.

Abbreviation 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide

POIREA M, M-diisopropylethylamine

M, M-dimethylformamide pM5o dimethylsulfoxide

Ra(arry)Si2 dichloro(1,1"-bisidiphenylphosphino)ferrocenipalladium!)

NMR 00 |Nuclear Magnetic Resonance Spectroscopy

Room temperature

Potassium peroxymonosulfate

ORI C High performance liquid chromatography

Synthesis of compounds of general formula I of this invention

Compounds of the general formula I are synthesized as indicated in the Scheme, with

A, VU, B? having the values given for the general formula I, above;

VZ, 02 mean the outgoing group; and

Oh! means an optionally protected MNe group or a leaving group. examples of a typical leaving group include, but are not limited to, a halogen atom, such as a chlorine, bromine, or iodine atom, or a C(O)rg group (where p is 0, 1, or 2 and

Ve is as specified for general formula I, above) as methylsulfonyl-, or triflate or nonaflate. oh oh oh oh! syu -x25--05 KO v' - v hi-f v - v shchy x IH o UP A MI A v? | in | in still shchi shchi se se se -- zh - - - 62 zm. і і ЧО в щі 2

MI M o IM A v | in? | in? day day sun day

II II o I A

Scheme

The scheme shows the ways that allow variations of BEZ, VU, Vb, 0, 02 and A during the synthesis.

Functional residues in KZ, VU, B", C, 02 and A can be converted at any suitable stage of synthesis.

However, other ways are also used to synthesize the desired compounds.

Compounds of formula X may be commercially available or may be synthesized by methods known to those skilled in the art, for example using methods described in

MO2007/38314A2.

The leaving group 27 can be introduced into compounds of general formula X, MI or PP by methods known to specialists in the field to obtain compounds of general formula IX, M or II. As an example, halogens can be introduced using halogenation reagents such as

M-iodosuccinimide (MI5), M-bromosuccinimide (MB5) or M-chlorosuccinimide (MC5), in an inert solvent such as, for example, M,M-dimethylformamide or 1-methylpyrrolidin-2-one, for example at a temperature range from room temperature to the boiling point of the solvent.

Compounds of the general formula I, IM or MI are obtained from compounds of the general formula II, M or IX by means of a condensation reaction between a reagent of the formula U-A, where A is as defined above, and U represents a suitable functional group by means of which the group A can be transferred on the OO group containing the carbon atom of the compound of formula II, M or IX. Examples of suitable functional groups for U in A-X include boronic acids A-B(OH)2 or boronic acid esters A-B(OC:1-C-alkyl)g5. These condensation reactions are carried out in the presence of suitable catalysts, such as, for example, palladium-based catalysts, for example, palladium (I) acetate, tetrakis(triphenylphosphine)palladium (0), bis(triphenylphosphine)-palladium (I) chloride or (1y1, -bisidiphenylphosphino)ferrocene)-dichloropalladium(II), and optionally suitable additives such as, for example, phosphines, such as P(oToi)z or triphenylphosphine, and optionally suitable bases, such as, for example, potassium carbonate, sodium 2-methylpropan-2-olate, tetrabutylammonium fluoride or tribasic potassium phosphate in a suitable solvent such as, for example, tetrahydrofuran.

Examples of such condensation reactions can be found in the Meia!I-Saiauea manual

Sto55-Soiriipd Keasiyop5", Agtip de Meige (Eadiog), Egapsoi5 Oivedetisn (Ediug) berietbreg 2004,

Mew Ipiegbsiepse IZVM: 978-3-527-30518-6.

Compounds of the general formula I, II, I or MI are prepared from a compound of the general formula IM, M, MI or MI by means of a condensation reaction using a reagent of the formula U-NH, where KZ is as defined above and U represents a suitable functional group by which Ez can be transferred to KU containing a carbon atom of a compound of the formula IM, M, MI or MI. Examples of suitable functional groups B for use in condensation reactions are given above for obtaining a compound of the general formula I, IM or MI from a compound of the general formula YII, M or IX.

Condensation reactions include metal-mediated condensation reactions such as Sonogashira condensation reactions with alkynes to introduce an alkyne, Heck condensation reactions with alkenes to introduce an alkene, Hartwig-Buchwald condensation reactions with amines to introduce an amine.

In X-BZ can also mean hydroxyl, which can be removed by suitable bases, for example, sodium hydride, in a suitable solvent, such as OM 5 O or tetrahydrofuran in the temperature range from room temperature to boiling temperature. The resulting nucleophiles, such as, for example, primary or secondary amines, alkoxides, thiolates or groups containing a carbon anion, are used to replace KK" in a compound of the general formula IM, M, MI or MI! to add secondary or tertiary amines, ethers, thioethers or groups attached to carbon atoms to obtain a compound of the general formula I, II, PI or MI.

Compounds of the general formula I, II, IP or MI containing primary or secondary amines, ethers or thioethers can also be prepared by Ullmann-type condensation reactions in the presence of suitable catalysts such as, for example, copper-based catalysts such as copper diacetate (I !) in the presence of a suitable base, for example cesium carbonate, starting with compounds of the general formula IM, M, MI or MI, where KU means a leaving group such as, for example, an iodine, bromine or chlorine atom. Optionally, suitable ligands such as M,M-dimethylglycine or hydrophenyl pyrrolidin-2-ylphosphonate can be added.

In the case when 0! means a leaving group, the introduction of the Co-CNeo group is carried out by nucleophilic substitution of C in a compound of the formula MII, MIP, YX or X, i.e., by reaction with suitable amines KR-СНе-МН" in the presence of a suitable base, such as, for example, OIREA, in a suitable solvent, such as M, M-dimethylformamide or 1-methylpyrrolidin-2-one, in the temperature range from room temperature to the boiling temperature of the solvent to give amines of the general formula I, IM, M or MI.

In the case when C means a leaving group, the introduction of the RB"-СНе group is carried out by a condensation reaction, where 0" in the compound of the formula МИЙ, MI, ХХ or X interacts with suitable amines К»-СНе-МН», optionally in the presence of a suitable catalyst such as Ragdbraz and

VIMAR, for example, and optionally with a suitable base, such as, for example, sodium tert-butylate in a suitable solvent, such as, for example, M,M-dimethylformamide or 1-methylpyrrolidin-2-one, to give amines of general formula I , IM, M or MI.

In the case when 0! means an optionally protected MNeo group, the introduction of the K?-CHe group, after deprotection of the MHe group, is carried out by reductive amination using an aldehyde of the formula O-CHE?, a suitable reducing agent, for example, sodium tris(acetato-kappaS) y(hydrido)borate or sodium cyanoborohydride in a suitable solvent such as, for example, acetic acid, in the temperature range from room temperature to the boiling point of the solvent.

Residues of the compound of formula I, II, PI, IM, M, MI, MI, MIP, IX or X may be optionally modified. For example, thioethers can be oxidized using oxidizing agents such as 3-chlorobenzenecarboperoxyacid, oxone, or dimethyldioxirane in an inert solvent such as dichloromethane or acetone, respectively. Depending on the stoichiometric ratio of the oxidizing agent and the above-mentioned sulfoxides or sulfonates or their mixtures.

Also, the compounds of formula I of the present invention can be converted to any salt as (610) described herein by any method known to those skilled in the art. Similarly,

any salt of the compound of formula I of this invention can be converted to the free compound by any method known to a person skilled in the art.

Compounds and intermediates obtained by the methods of the invention may require purification.

The purification of organic compounds is well known to those skilled in the art and therefore there are several ways to purify the same compound. In some cases, cleaning may not be necessary. In some cases, compounds can be purified by crystallization. In some cases, impurities are removed by stirring using a suitable solvent. In some cases, the compounds can be purified by chromatography, in particular flash chromatography, using, for example, prepackaged silica gel cartridges, for example, produced by Zeragia5, such as silica gel IsoYsheF RiIazp or Ivoiseft BRiazp MN" in combination with a suitable chromatographic system, such as a RiazPpItavbieg I (Beragivie) or Izoiega (Vioiade), and eluents such as, for example, hexane/E(OAc or OSM/methanol gradients. In some cases, compounds can be purified by preparative HPLC using, for example, an automatic Umayeg5 purifier equipped with diode array detector and/or mass spectrometer with on-line electrospray ionization in combination with a suitable prepacked reverse phase column and eluents such as, for example, gradients of water and acetonitrile, which may contain additives such as trifluoroacetic acid, formic acid or aqueous solution of ammonia.

Examples

Analytical UEC-MS (ultra-efficient liquid chromatography - mass spectrometry) was carried out as follows:

Method A: System: Asdiyu UEC (UMageg5) with ROA detector and Umayege 293 mass spectrometer; Column: Asdiyu VEN C18 1.7μm 2.1 x 50mm; Temperature: 60 "C; Solvent A: Water x 0.1 96 formic acid; Solvent B: Acetonitrile; Gradient: 99 Fo A -2 1 Fo A (1.6 min.) 2? 1956 A (0.4 min. ); Flow: 0.8 mL/min; Injection volume: 1.0 µL (0.1 mg - 1 mg/mL sample concentration);

Detection: ROA scanning range 210-400 nm - Ryhei and E5I (w), scanning range 170-800 t/2

General:

All reactions were carried out in an argon atmosphere in a degassed solvent, unless otherwise indicated.

Example 1 1-36-K2E/2)-But-2-en-2-yl|-3-(4-(2-cyclopropyl-1H-imidazol-5-yl)uphenyl imidazo|1,2-b| Ipyridazin-8-ylylamino)-2-methylpropan-2-ol one and one

Fo s si zm Y and zmi ftmn tin o u

A mixture of 47.5 MG (112 μmol) 1-(T6-chloro-3-I4-(2-cyclopropyl-1H-imidazol-5-yl)uphenylimidazo|1,2-b|pyridazin-8-ilyamino)-2 -methylpropan-2-ol, which was prepared according to Intermediate Example Ta, 47.3 mg of (2E/2)-but-2-en-2-ylboronic acid, 1.6 ml of n-propanol, 228 μl of 1-methylpyrrolidine- 2-one, 168 μl of a 2M aqueous solution of potassium carbonate, 1.47 mg of triphenylphosphine, and 7.9 mg of bis(triphenylphosphine)palladium(I) chloride were stirred at 120 °C for 2 hours under microwave irradiation. The solvent was removed and the residue was purified by chromatography with obtaining 20.7 mg (40 95) of the compounds indicated in the title. 1H-NMR (0M50-a6): b- 0.81-0.91 (4H), 1.15 (6H), 1.72 (ZH), 1.93 (1H), 2.05 (ZH), 3.13--3.26 (2H), 4.75-4.77 (1H), 5.73 (1H), 6.16-6, 18 (1H), 6.75 (1H), 7.19-7.45 (1H), 7.65-7.76 (2H), 7.90--7.95 (1H), 8.06- 8.14 (2H), 11.79--12.09 (1H) ppt.

Intermediate Example 1a 1-(16-Chloro-3-(4-(2-cyclopropyl-1H-imidazol-5-yl)phenylimidazo|1,2-b|Ipyridazine-8-ylamino)-2-methylpropane-2- ol

Gee) he doesn't do everything with us! fun lacquer

A mixture containing 700 MG (1.91 mmol) of 1-(b-chloro-3-iodoimidazo|/1,2-b|Ipyridazin-8b-yl)amino|-2-methylpropan-2-ol, which was obtained according to with Intermediate Example 156, 610 mg of (4-(2-cyclopropyl-1H-imidazol-5-iluphenyl)oronic acid, which was obtained according to Intermediate Example 1a, 156 mg of (1,1,-bisidiphenylphosphino)ferrocene)-dichloropalladium (I) , 2.86 ml of a 2M aqueous solution of tribasic potassium phosphate and 8.2 ml of tetrahydrofuran were stirred at 45 "C for 12 hours. Water was added and the mixture was extracted with ethyl acetate and methanol. The organic layer was washed with brine and dried over sodium sulfate. After filtering and removing solvent, the residue was purified by chromatography to obtain 345 mg (43 Fo) of the title compound.

Intermediate Example 16 1-(6-Chloro-3-iodoimidazo|1,2-b|Ipyridazin-8-yl)amino|-2-methylpropan-2-olone

That's all, Fe! with more

AND

895 mg of M, M-dimethylformamide was added to a solution of 1.20 g (3.35 mmol) of 8-bromo-b-chloro-3-iodoimidazo|1,2-b|Ipyridazine, which was obtained according to Intermediate Example 1c in 24 ml of M, M-dimethylformamide 1-amino-2-methylpropan-2-ol, and the mixture was stirred at 40 "C overnight. Water was added and the mixture was extracted with dichloromethane and methanol. The organic phase was washed with water and dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography with obtaining 798 mg (65 90) of the title compound.

Intermediate Example 1c 8-bromo-6-chloro-3-iodoimidazo|!1,2-b|Ipyridazine

Vg Ve prisoner ' Fe; si and sim

A mixture containing 100 g (430 mmol) of 8-bromo-b-chloroimidazo|(1,2-5|Ipyridazine, which was obtained according to the procedure described in О052007/78136 (М/МО2007/38314), 145 g of M-iodosuccinimide , 5 wt. of 95 conc. hydrochloric acid and 1 L of trichloromethane were refluxed for b hours. 20 g of M-iodosuccinimide was added and heating was continued for an additional 3 hours. The precipitate was removed and the filtrate was washed with 1 M sodium hydroxide solution, brine and dried over sodium sulfate. After filtration and removal of the solvent, isopropyl ether was added, and the residue was stirred at 23 "C overnight.

The precipitate was filtered off and dried to give 66.6 g (43 95) of the title compound.

Intermediate Example 14 2-Cyclopropyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)uphenyl/|-1H-imidazole

Vg from o-v - niya dtMn in YtMn still

A mixture containing 42.1 g (160 mmol) of 5-(4-bromophenyl)-2-cyclopropyl-1H-imidazole, which was obtained according to Kk! Intermediate Example 1e, 60.9 g of 4,4,A445,5,5,5'-octamethyl-2,27-6i-,3,2-dioxaborolane, 3.05 g of dicyclohexyl (24,6-triisopropylbiphenyl-2- ilophosphine, 1.46 g of tris-(dibenzylideneacetone)-dipalladium(0), 23.5 g of potassium acetate and 267 ml of 1,4-dioxane were stirred at 110 C for 4 hours. After cooling to 23 "C, ethyl acetate and 1 M hydrogen chloride acid was added and the pH was adjusted to 8.0 by adding sodium hydroxide solution 595. The mixture was extracted with ethyl acetate.

The organic layer was washed with brine and dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by crystallization to give 33.5 g (67 95) of the title compound.

Intermediate Example 1e 5-(4-Bromophenyl)-2-cyclopropyl-1H-imidazole

Ve

Ve --

Y7TMn o Vg u

To a solution of 89.0 g (320 mmol) of 2-bromo-1-(4-bromophenylethanone in 2.0 L of M,

To M-dimethylformamide was added cyclopropanecarboxymidamide hydrochloride, 132.8 g of potassium carbonate, and the mixture was stirred at 23 "C overnight. After removal of the solvent, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. After filtration and removal solvent, the residue was purified by crystallization to obtain 42.1 g (50 Fo) of the title compound.

Example 2 1-33-(4-(2-Cyclopropyl-1H-imidazol-5-iluphenyl|-6-K1 E/2)-prop-1-en-1-yl imidazo|1,2-b|Ipyridazine -8-ylylamino)-2-methylpropan-2-ol one one

47.5 MG (112 μMOL) 1-(T6-chloro-3-I4-(2-cyclopropyl-1H-imidazol-5-yl) )uphenylimidazo|1,2-b|pyridazin-8-ylamino)-2-methylpropan-2-ol, which was obtained according to Intermediate Example a, was converted analogously to Example 1, using (1E/2)-prop-1-ene- 1-ylboronic acid, obtaining after processing and purification 34.1 mg (71 95) of the title compounds. 1H-NMR (0M50-a6): b- 0.81-0.93 (4H), 1.16 (6H), 1.83-1.98 (4H), 3:13--3.26 (2H ), 4.76 (1H), 6.34-6.46 (2H), 6.59-6.78 (2H), 7.19-4-7.45 (1H), 7.66-7, 76 (2H), 7.85--7.91 (IN), 8.08-8.15 (2H), 11.79--12.11 (1H) ppt.

Example C 3-I(4-(2-Cyclopropyl-1H-imidazol-5-iluphenyl|-M-isobutyl-b-(pyridin-4-yl)imidazo|1,2-b|Ipyridazin-8-amine

Fola) satiety 7 ot» zim 7 ---sh-» M rochn ftmn in vk 50 MG (123 МКМОЛ) b-chloro-3-I4-(2-cyclopropyl-1 H-imidazol-5-iluphenyl|- M-isobutylimidazo|1,2-b|Ipyridazine-8-amine, which was obtained according to Intermediate Example 3, was converted analogously to Example 1 using pyridine-4-ylboronic acid, obtaining after treatment and purification 10.9 mg (20 Fo ) of the title compound. 1H-NMR (OM5O-ab): 0- 0.82-0.91 (4H), 0.94 (6H), 1.94 (1H), 2.04 (1H), 3 ,26 (2H), 6.74 (1H), 7.49 (1H), 7.68 (1H), 7.82 (2H), 7.98 (1H), 8.05 (2H), 8, 16 (2H), 8.72 (2H), 11.82--12.13 (1H) ppt.

Intermediate Example According to b-Chloro-3-(4-(2-cyclopropyl-1H-imidazol-5-yl)uphenyl|-M-isobutylimidazo|1,2-b|Ipyridazin-8-amine

And Iye Fe

200 mg (570 μmol) of 6b-chloro-3-iodo-M-isobutylimidazo|1,2-5|pyridazine-8-amine, which was obtained according to Intermediate Example ZB, was converted similarly to Intermediate

Example And with obtaining after processing and purification 114 mg (49 95) of the title compound.

Intermediate Example ZB b-Chloro-3-iodo-M-isobutylimidazo|1,2-5|Ipyridazine-8-amine

Ver r y zh -f se sim y y ! sieve 200 mg (558 μmol) of 8-bromo-6b-chloro-3-iodoimidazo|1,2-b|pyridazine, which was obtained according to

Intermediate Example 11c was converted analogously to Intermediate Example 16 using 2-methylpropan-1-amine to give, after treatment and purification, 188 mg (96 95) of the title compound.

Example 4 3-I(4-(2-Cyclopropyl-1H-imidazol-5-iluphenyl)-6-(pyridin-4-yl)-M-(25)-tetrahydrofuran-2-ylmethylimidazo|1,2-5 |Ipyridazine-8-amine

S S kn kn

Fo day s zi and t» zi J

Ma ptn schu tMn mu mu mu

50 MG (115 μMOL) b-chloro-3-I(4-(2-cyclopropyl-1H-imidazol-5-iluphenyl|I-M-(25)-tetrahydrofuran-2-ylmethylimidazoi(1, 2-B| Ipyridazine-8-amine, which was prepared according to Intermediate Example 4a, was converted analogously to Example 1 using pyridine-4-ylboronic acid to give, after work-up and purification, 4.4 mg (8 95) of the title compound. 1H-NMR ( SOSIS): b- 1.01-1.12 (4H), 1.73 (1H), 1.95 (2H), 2.09 (2H), 3.44 (1H), 3.53 (1H) , 3.78 (1), 3.92 (1H), 4.21 (1H), 6.50 (1H), 7.21 (1H), 7.70 (2H), 7.74 (1H), 7.85 (2H), 8.07 (2H), 8.17 (1H), 8.63 (2H) ppt.

Intermediate Example 4a b-Chloro-3-(4-(2-cyclopropyl-1H-imidazol-5-iluphenyl|-M-(25)-tetrahydrofuran-2-ylmethylimidase 911,2-5B|Ipyridazin-8-amine

WITH

(f: pl

Mn atm / s ziti ! 232 MG (613 μMOL) of b-chloro-3-iodo-N-(25)-tetrahydrofuran-2-ylmethylimidazo|1,2-5|pyridazine-8-amine, which was obtained according to Intermediate Example 4B, was converted similarly Intermediate

Example And with obtaining after processing and purification 118 mg (44 95) of the title compound.

Intermediate Example 4B b-Chloro-3-iodo-M-(25)-tetrahydrofuran-2-ylmethylimidazo(1,2-b|Ipyridazin-8-amine

Fe, and Mn see Fe! still

AND

500 mg (1.40 mmol) of 8-bromo-b-chloro-3-iodoimidazo|1,2-5|pyridazine, which was obtained according to

Intermediate Example 1c was converted analogously to Intermediate Example 16, using 1-(25)-tetrahydrofuran-2-yl|methanamine, obtaining after treatment and purification 497 mg (94 9b5) of the title compound.

Example 5 3-(4-(2-Cyclopropyl-1H-imidazol-5-iluphenyl)-6-(pyridin-4-yl)-M-(2A)-tetrahydrofuran-2-ylmethylimidazo|1,2-5| Ipyridazine-8-amine i i

MN MN

Fo dna si zm Y s zm Y

50 MG (115 μMOL) b-chloro-3-I(4-(2-cyclopropyl-1H-imidazol-5-yl)uphenyl|-M-(2A)-tetrahydrofuran-2- ylmethylimidazo|1, 2-B|Ipyridazine-8-amine, which was obtained according to Intermediate Example 5a, was converted similarly to Example 1, using pyridine-4-ylboronic acid, obtaining after treatment and purification 6.1 mg (11 95) of the specified in the compound header.

1H-NMR (SOSIS): b- 1.01-1.12 (4H), 1.73 (1H), 1.95 (2H), 2.09 (2H), 3.44 (1H), 3, 53 (1H), 3.78 (1), 3.92 (1H), 4.21 (1H), 6.50 (1H), 7.21 (1H), 7.70 (2H), 7.74 (1H), 7.85 (2H), 8.07 (2H), 8.17 (1H), 8.63 (2H) ppt.

Intermediate Example 5a b-Chloro-3-(4-(2-cyclopropyl-1H-imidazol-5-iluphenyl|-M-(2A)-tetrahydrofuran-2-ylmethylimidase 911,2-5B|Ipyridazin-8-amine no

MN still se re sotu sake sizi ! ftMn lac 247 MG (652 μMOL) b-chloro-3-iodo-M-(2HA)-tetrahydrofuran-2-ylmethylimidazo(1,2-b|Ipyridazin-8b-amine, which was obtained according to Intermediate Example 5B, was converted similarly Intermediate

Example And with the receipt after processing and purification of 112 mg (39 95) of the title compound.

Intermediate Example 5B b-Chloro-3-iodo-M-(2A)-tetrahydrofuran-2-ylmethylimidazo|1,2-b|pyridazine-8-amine

Ver re and MN vi i se

SI M s 7! 5 si and ! 500 mg (1.40 mmol) of 8-bromo-b-chloro-3-iodoimidazo|1,2-5|pyridazine, which was obtained according to

Intermediate Example 1c was converted analogously to Intermediate Example 16, using 1-(2B)-tetrahydrofuran-2-ylmethanamine, to obtain after treatment and purification 513 mg (97 95) of the title compound.

Example 6 3-(4-(2-Cyclopropyl-1H-imidazol-5-yl)uphenyl|-6-(4-fluorophenyl)-M-(3,3,3-trifluoropropyl)imidazo|1,2-b |Ipyridazin-8-amine and i

In U

MN MN

Fo dn M sit ki and winter

40 mg (90 μmol) b-chloro-3-(4-(2-cyclopropyl-1H-imidazol-5-yl)phenyl|-M-(3,3,3-trifluoropropyl)imidazo( 1,2-b|Ipyridazine-8-amine, which was obtained according to

Intermediate Example ba was converted similarly to Example 1 using (4-fluorophenyl)boronic acid, with the result after treatment and purification of 3.6 mg (7 95) of the title compound. 1H-NMR (SOSIS): b- 0.97-1.09 (4H), 2.00 (2H), 2.59 (2H), 3.73 (2H), 5.97 (1H), 6, 37 (1Н), 07.14-7.26 (ЗН), 7.75-7.84 (ЗН), 7.96 (2Н), 8.13 (2Н) ppt.

Intermediate Example b-Chloro-3-(4-(2-cyclopropyl-1H-imidazol-5-iluphenyl)|-M-(3,3,3-trifluoropropyl)imidazo|1,2-b|Ipyridazine-8 -amin ve

In in MN with M with more, ! 330 mg (845 μmol) of 6b-chloro-3-iodo-M-(3,3,3-trifluoropropyl)imidazo(|1,2-b|Ipyridazine-8-amine, which was obtained according to Intermediate Example 6p , converted similarly to Intermediate

Example And with the receipt after processing and purification of 220 mg (58 95) of the title compound.

Intermediate Example br b-Chloro-3-iodo-M-(3,3,3-trifluoropropyl)imidazo|1,2-b|Ipyridazin-8-amine

IS

IS

Ve U se MN

FU -f Fo

SI M p 7

And SU si and

AND

1.96 g (5.46 mmol) of 8-bromo-b-chloro-3-iodoimidazo|1,2-b|Ipyridazine, which was obtained according to

Intermediate Example 1c was converted similarly to Intermediate Example 16, using 3,3,3-trifluoropropan-1-amine, to obtain after treatment and purification 1.58 g (74 Fo) of the title compound.

Example 7

M-cyclopropyl-4-(6-(4-fluorophenyl)-8-(2-hydroxy-2-methylpropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamidone Ge)

Fo dn is hearty 4 zim 4

IS

M M

(c) (c) v i b 76 mg (184 μmol) 4-(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)" M-Cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 1 using (4-fluorophenyl)boronic acid to give, after work-up and purification, 25.7 mg (30 95) of the title compound. 1H -NMR (SOSIS/С0О300): b- 0.61 (2Н), 0.86 (2Н), 1.37 (6Н), 2.47 (ЗН), 2.88 (1Н), 3.33 (2Н ), 6.38 (1Н), 7.13 (2Н), 7.39 (1Н), 7.69 (1Н), 7.83-7.91 (ЗН), 7.94 (1Н) ppt.

Intermediate Example 7a 4-i6-Chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl-

M-cyclopropyl-2-methylbenzamidon weight 2-8

МН зи --ь ом с яти

M

(in)

b

700 MG (1.91 mmol) of 1-(b-chloro-3-iodoimidazo|/1,2-b|Ipyridazin-8b-yl)amino|-2-methylpropan-2-ol, which was obtained according to Intermediate Example 16 , was converted analogously to Intermediate Example 1a, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl/benzamide, which was obtained according to Intermediate

Example 706, with treatment and purification yielding 360 mg (46 95) of the title compound.

Intermediate Example 7 years

M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3 2-dioxaborolan-2-yl)benzamide (c) points

O.V 75 c

To a solution of 260 g (1.02 mol) of 4-bromo-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7c, in 2 l of dioxane at 23"С, 390 g of bis-(pinacolato)-diboron was added, 19 .5 g of 2-dicyclohexylphosphino-2",4",6'-triisopropylbiphenyl, 150 g of potassium acetate and 9.37 g of tris-(dibenzylideneacetone)-dipalladium(0), and the mixture was refluxed for 6 hours After cooling to 23 °C, water and ethyl acetate were added, and the mixture was stirred for 15 min. The organic phase was washed with water, dried over sodium sulfate, filtered and evaporated. The residue was purified by chromatography to obtain 308 g (56 95) of the title compound. 1H-NMR (300 MHz, SOSIZ): b - 0.59 (2H), 0.85 (2H), 1.33 (6H), 2.41 (ZH), 2.87 (1H), 5.94 (1H), 7.28 (1H), 7.60 (1H), 7.63 (1H) ppt.

Intermediate Example 7c 4-bromo-N-cyclopropyl-2-methylbenzamide (c) to

Ve

796 g of cyclopropanamine and 320.9 g of EOS were added to a stirred solution of 300 g (1.4 mol) of 4-bromo-2-methylbenzoic acid in 8.4 l of dichloromethane at 23"C. After stirring overnight, the solution was washed with water and aq. phase was extracted with dichloromethane. The combined organic phases were dried over sodium sulfate, filtered and evaporated. The residual solid was triturated with isopropyl ether, filtered, washed and dried in vacuo to give 260 g (73 95) of the title compound.

Example 8 1-(13-(4-(2-Cyclopropyl-1H-imidazol-5-yl)phenyl|-6-(4-fluorophenyl)imidazo

P,2-B|Ipyridazin-8-ilyamino)-2-methylpropan-2-ol one one

Fo dna

SI m" m"

E ftMn ftMn in mu 70 MG (166 μMOL) 1-((6b-chloro-3-(4-(2-cyclopropyl-1H-imidazol-5-yl)phenyl imidazo|1,2-b|Ipyridazine-8 -ilamino)-2-methylpropan-2-ol, which was obtained according to Intermediate

Example 1 was converted analogously to Example 1, using (4-fluorophenyl)boronic acid, to obtain after treatment and purification 4.9 mg (6 95) of the title compound. 1H-NMR (0M5O-ab): 0- 0.80-0.94 (4H), 1.18 (6H), 1.93 (1H), 3.39 (2H), 4.79 (1H), 6.77 (1H), 6.86 (1H), 7.21--7.48 (1H), 7.85 (2H), 7.70--7.81 (2H), 7.94-- 7.99 (1H), 8.06-8.24 (4H), 11.81-12.12 (IN) ppt.

Example 9 1-(13-(4-(2-Cyclopropyl-1H-imidazol-5-iluphenyl|-6-(pyridin-4-yl)imidazo|1,2-bB|pyridazine-8-ylamino)-2 -methylpropan-2-ol on on

Fo dna si mi / ; with zy J

M du tMn ptn u mu mu 47.5 mg o (112 μmol) 1-(/6-chloro-3-(4-(-2-cyclopropyl-1H-imidazol-5-yl)uphenyl|imidazo

P,2-VIpyridazin-8-ylamino)-2-methylpropan-2-ol, which was obtained according to Intermediate

Example 1 was converted analogously to Example 1, using pyridine-4-ylboronic acid, to obtain after treatment and purification 12.5 mg (23 95) of the title compound. 1H-NMR (0M5O-ab): 6- 0.82-0.92 (4H), 1.19 (6H), 1.93 (1H), 3.42 (2H), 4.79 (1H), 6.89 (1H), 7.01 (IN), 7.22--7.49 (1H), 7.72--7.83 (2H), 7.97-8.08 (ZH), 8 ,15--8.23 (2H), 8.73 (2H), 7.82-41213 (1H) ppt.

Example 10

M-cyclopropyl-2-methyl-4-(6-(1-methyl-1H-pyrazol-5-yl)-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b |pyridazin-3-yl)ibenzamid

E sa vi

IS

MN

МН уФ о з МИ их см -- з, 2nd и: M о. them, oh-K?

M on 40 mg (91 μmol) 4-(6b-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo/1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2- methylbenzamide, which was obtained according to Intermediate Example 1ba, was converted similarly to Example 1, using 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole , after processing and purification, 7.2 mg (16 Fo) of the title compound was obtained. 2.58 (2H), 2.93 (1H), 3.72 (2H), 4.20 (ZH), 5.95 (1H), 6.01 (1H), 6.28 (1H), 6 .66 (1H), 7.42 (1H), 7.55 (1H), 7.79 (1H), 7.85 (1H), 7.89 (1H) ppt.

Intermediate Example 1ba 4-(6-Chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)y-

M-cyclopropyl-2-methylbenzamide ve

In the heart of Mn

RU Fo

МН ХТ se ---« s M s zt o.

M another 500 mg (1.28 mmol) of b-chloro-3-iodo-M-(3,3,3-trifluoropropyl)imidazo|/1,2-b|Ipyridazine-8-amine, which was obtained according to the Intermediate Example 6B, converted similarly to Intermediate

Example 1a, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, obtaining after treatment and purification 139 mg (25 Fo ) of the title compound.

Example 11 3-(3-Amino-1H-indazol-b-yl)-M-isobutyl-b6-phenylimidazo|1,2-5|pyridazine-8-amine

S chn - 2 i M

Sh ) -- and. we and SM M Mn,

To a solution of 46 mg (119 μmol) of 2-fluoro-4-I(I8-(isobutylamino)-6-phenylimidazo|1,2-pyridazin-3-yl|!bsenzonitrile, which was obtained according to Intermediate Example 11a in 2 .5 ml of n-butanol, 232 μl of hydrazine hydrate was added, and the mixture was heated at 120 °C overnight.

The precipitate was filtered, washed with 2-propanol and dried to give 26.5 mg (53 Obov) of the title compound. 1H-NMR (0M50-ab): 0- 0.94 (6H), 2.04 (1H), 3.26 (2H), 5.33 (2H), 6.63 (1H), 7.46- 7.58 (5H), 7.74 (1H), 8.00 (1H), 8.07 (2H), 8.38 (1H), 11.53 (1H) ppt.

Intermediate Example 11a 2-fluoro-4-I8-(isobutylamino)-6-phenylimidazo(1,2-b|Ipyridazin-3-yl|Irenzonitrile se dn M

SI zm ) zm )

100 mg (291 μmol) of 4-(b-chloro-8-(isobutylamino)imidazo|1,2-BI pyridazin-3-yl|-2-fluorobenzonitrile, which was obtained according to Intermediate Example 116, was converted similarly Example 1, using phenylboronic acid, to obtain after processing and purification 49 mg (44 95) of the title compound.

Intermediate Example 116 4-(b-Chloro-8-(isobutylamino)imidazo|!1,2-b|Ipyridazin-3-yl|-2-fluorobenzonitrile to Si

MN Fo

Fo 65620 SI zm / s it

AND

There are 500 mg (1.43 mmol) of 6-Chloro-3-iodo-N-isobutylimidazo|1,2-b|Ipyridazine-8-amine, which was obtained according to Intermediate Example ZB, converted similarly to Intermediate

Example 1a using (4-cyano-3-fluorophenyl)boronic acid, yielding after treatment and purification 217 mg (44 95) of the title compound.

Example 12

M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-phenylimidazo|1,2-b|pyridazin-3-yl)y-2-methylbenzamidone one

Fo day sim" ; 0-0 zm ; oi oi 250 mg (604 μmol) 4-(6-Chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|!1,2-b|pyridazine-3 -yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 1 using phenylboronic acid, obtaining after treatment and purification 48 mg (17 95) of the title compound.

1H-NMR (0M5O-ab): b- 0.51 (2H), 0.66 (2H), 1.18 (6H), 2.39 (ZH), 2.81 (1H), 3.39 ( 2H), 4.78 (1), 6.80 (1H), 6.90 (1H), 7.40 (1H), 7.46-7.55 (ZH), 8.00-8.07 ( 4H), 8.13 (1H), 8.30 (IN) ppt.

Example 13

M-cyclopropyl-4-(8-(isobutylamino)-6-(pyridin-4-yl)imidazo|(1,2-5|Ipyridazin-3-yl|renzolcarbotiomide and dn; c zym Y - c" ; c zim J

Mo Mag

In vy

A mixture of 40 MG pov μmol) 4-(8-(isobutylamino)-6-(pyridin-4-yl)imidazo

P,2-5-Ipyridazin-3-yl|rsSenaldehyde, which was obtained according to Intermediate Example 13a, 3.45 mg of sulfur, 37 μl of cyclopropanamine and 250 μl of dimethylsulfoxide were heated at 100 "C under microwave irradiation for 4 hours. The mixture was stirred at 90 " C overnight, the solvent was evaporated and the residue was purified by chromatography to give 4.8 mg (10 95 ) of the title compound. 1H-NMR (SOSIS/CO300): b- 0.80 (2H), 1.03 (2H), 1.08 (6H), 2.08 (1H), 3.21 (2H), 3.40 ( 1H), 6.40 (1H), 7.78-7.89 (5H), 8.12 (2H), 8.69 (2H) ppt.

Intermediate Example 1Za 4-I(8-(Isobutylamino)-6-(pyridin-4-yl)imidazo|(1,2-b|pyridazin-3-yl|rensaldehyde o C 4 F r

There is chh zm - in; with zm /

Ma : M. same c) :

To a solution of 63 mg (152 μmol) 3-I4-(1,3-dioxolan-2-yl)uphenyl|-M-isobutyl-6b-(pyridin-4-yl)imidazo|1,2-b|Ipyridazin-8 -amine, which was obtained according to Intermediate Example 136, in 2.8 ml of acetone, 190 μl of 4M hydrochloric acid was added, and the mixture was stirred at 23" for 2 hours. Saturated bicarbonate solution was added, and the mixture was extracted with dichloromethane. The organic phase was dried over sulfate After filtration and removal of the solvent, the residue was purified by chromatography to give 41 mg (73 95) of the title compound.

Intermediate Example 13p 3-I4-(1,3-Dioxolan-2-yl)uphenyl|-M-isobutyl-6-(pyridin-4-yl)imidazo(1,2-b|Ipyridazin-8-amine /Fo AX m sim" / --yu u zm /

Ma ef ef 105 MG (282 μmol) b-chloro-3-I4-(1,3-dioxolan-2-iluphenyl|-M-isobutylimidazo

P,2-B|Ipyridazine-8-amine, which was obtained according to Intermediate Example 13c, was converted analogously to Example 1 using pyridine-4-ylboronic acid, obtaining after treatment and purification 64 mg (55 95) of the title compound.

Intermediate Example 13c b6-Chloro-3-I4-(1,3-dioxolan-2-iluphenyl|-M-isobutylimidazo|1,2-b|Ipyridazin-8-amine is that ac

MN from M

Fo --e sm with dad

AND

07 500 mg o (1.43 mmol) 6-Chloro-3-iodo-N-isobutylimidazo|1,2-b|Ipyridazine-8-amine, which was obtained according to Intermediate Example ZB, was converted similarly to Intermediate

Example 1a, using 2-I4-(1,3-dioxolan-2-yl)phenyl|)|-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, obtaining after treatment and purification 314 mg (47 95) of the title compound.

Example 14

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-phenylimidazo|1,2-b|pyridazin-3-yl)benzamidon on se nie s zm / - --- zm /

M M

(c) (c) (o b h 176 mg (440 μmol) 4-(6b-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl )"M-cyclopropylbenzamide, obtained according to Intermediate Example 14a, was converted analogously to Example 1, using phenylboronic acid, yielding after treatment and purification 42 mg (21 95) of the title compound. 1H-NMR (0M5O-46): 6- 0.56 (2H), 0.67 (2H), 1.19 (6H), 2.85 (1H), 3.40 (2H), 4.78 (1H), 6.82 (1), 6 .93 (1H), 7.46-7.55 (ZH), 7.93 (2H), 8.05 (2H), 8.09 (1H), 8.33 (2H), 8.45 (1H ) ppm

Intermediate Example 14a 4-(6-Chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)"M-cyclopropylbenzamidone

HE and M

MH with MAY --- cm si zy (in g h b 976 MG (2.66 mmol) 1-(b-chloro-3-iodoimidazo|/1,2-b|Ipyridazin-8b-yl)amino|-2- methylpropan-2-ol, which was obtained according to Intermediate Example 16, was converted analogously to Intermediate Example Ta using (|4-(cyclopropylcarbamoyl)uphenyl|boronic acid) to give, after treatment and purification, 602 mg (57 95) of the title compound.

Example 15

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(methylsulfanyl)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamidone y/ Fo/Fo with zm Y z zm Y

M M more shchi

To a solution of 83 mg (201 μmol) of 4-/(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

In Example 7a, 70 mg of sodium methanethiolate was added to 1.0 ml of dimethyl sulfoxide, and the mixture was heated under microwave irradiation at 70 "С for an hour. The mixture was poured into water and extracted with dichloromethane and methanol. The organic layer was washed with brine and dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by recrystallization to give 46.7 mg (55 95) of the title compound.

Example 16 3-(4-(2-Cyclopropyl-1H-imidazol-5-iluphenyl|-6-K1E)-prop-1-en-1-yl|-

M-(3,3,3-trifluoropropyl)imidazo|1,2-b|Ipyridazin-8-amine

She in

In U

MN MN

Pho is not

35 MG (78 µmol) b-chloro-3-(4-(2-cyclopropyl-1H-imidazol-5-yl)phenyl|-M-( 3,3,3-trifluoropropyl)imidazo(1,2-b|Ipyridazin-8-amine, which was obtained according to

Intermediate Example ba was converted similarly to Example 1, using (1E)-prop-1-en-1-ylboronic acid, obtaining after processing and purification 3.6 mg (10 95) of the title compound. 1H-NMR (SOSIS): b- 0.95-1.04 (4H), 1.95 (ZH), 2.00 (1H), 2.55 (2H), 3.62 (2H), 6, 10 (1H), 6.46 (1H), 6.61 (1H), 7.16 (1H), 7.67 (1H), 7.70 (2H), 8.05 (2H) ppt.

Example 17

M-cyclopropyl-4-18-((2-methoxy-2-methylpropyl)amino|-6-(pyridin-4-yl)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide 07 07 se l) s zm Y est zm Y

Shield

М M pure 60 mg (140 μmol) 4-(6-Chloro-8-(2-methoxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 17a, was converted analogously to Example 1, using pyridine-4-ylboronic acid, 3 to give, after work-up and purification, 18.7 mg (28 95) of the title compound. b- 0.64 (2Н), 0.90 (2Н), 1.33 (6Н), 2.54 (ЗН), 2.93 (1Н), 3.28 (ЗН), 3.38 (2Н) , 6.11 (1H), 6.18 (1H), 6.42 (1H), 7.44 (1H), 7.80-7.85 (ZH), 7.92 (1H), 8.00 (1H ), 8.71 (2H) ppt.

Intermediate Example 17a

4-6-Chloro-8-(2-methoxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)"N-cyclopropyl-2-methylbenzamide

And -tk om / si zani

M more 145 MG (380 μMOL) b-chloro-3-iodo-N-(2-methoxy-2-methylpropyl)imidazo|1,2-b|Ipyridazin-8-amine, which was obtained according to Intermediate Example 17p, was converted analogously to Intermediate Example 1a, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, yielding after work-up and purification 131 mg ( 81 Fo) of the compound indicated in the title.

Intermediate Example 17b-Chloro-3-iodo-M-(2-methoxy-2-methylpropyl)imidazo|1,2-b|pyridazin-8-amine o

Vg ve sbsyu Fo

I x si -f

AND

250 mg (698 μmol) of 8-bromo-6b-chloro-3-iodoimidazo|1,2-b|pyridazine, which was obtained according to

Intermediate Example 1c was converted similarly to Intermediate Example 16, using 2-methoxy-2-methylpropan-1-amine, to obtain after treatment and purification 260 mg (98 95) of the title compound.

Example 18

M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-(methylsulfonyl)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamidone one

Fe Fe i o, U vm / RV m / (c)

M M

(c) (c) h b b

To a solution of 38.7 mg (91 μmol) of M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino|-6-(methylsulfanyl)imidazo|1,2-b|Ipyridazin-3-yl- 2-methylbenzamide, which was obtained according to Intermediate Example 15 in 1.2 ml of M,M-dimethylformamide, 168 mg of oxone was added, and the mixture was stirred at 23 C for 2.5 days. Water was added and the mixture was extracted with dichloromethane. The organic phase was washed with water and dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to give 18.5 mg (39,905) of the title compound. 1H-NMR (0M50O-ab): b- 0.50 (2H), 0.65 (2H), 1.15 (6H), 2.37 (ЗН), 2.680 (1Н), 3.34 (2Н), 3.38 (ЗН), 4.79 (1Н), 6.76 (1Н) , 7.40 (1H), 7.71 (1H), 7.95 (1H), 7.99 (1H), 8.16 (1H), 8.32 (1H) ppt.

Example 19

M-cyclopropyl-4-(6-(4-fluorophenyl)-8-(2-hydroxy-2-methylpropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)benzamidone one

Fo day M satiy i zim 4

IS

M M only 200 mg (500 μmol) of 4-(6b-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)"M-cyclopropylbenzamide, which was obtained according to Intermediate Example 14a, was converted analogously to Example 1 using (4-fluorophenyl)boronic acid to give after work-up and purification 136 mg (59 95) of the title compound. 1H-NMR (0M5O-46): b- 0.56 (2H), 0.68 (2H), 1.18 (6H), 2.85 (1H), 3.39 (2H), 4.79 (1H), 6.81 (1H), 6 .94 (1H), 7.35 (2H), 7.93 (2H), 8.09 (1H), 8.11 (2H), 8.91 (2H), 8.46 (1H) ppt.

Example 20

M-cyclopropyl-4-/6-(2-(hydroxymethyl)phenyl)|-8-(3,3,3-trifluoropropyl)amino imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide and and

In U

MN MN se la) s zm / --kf zm / on

M M chykh Chek 172 mg (393 μmol) 4-16-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)y"M-cyclopropyl -2-methylbenzamide, which was obtained according to Intermediate Example 1ba, was converted analogously to Example 1 using (|2-(hydroxymethyl)phenyl|boronic acid, obtaining after work-up and purification 29.1 mg (14 95) of the title compound. 1H-NMR (SOSIS): b- 0.58 (2H), 0.85 (2H), 2.48 (3H), 2.58 (2H), 2.88 (1H), 3.72 (2H) , 3.96 (1H), 4.41 (2H), 6.16 (1H), 6.19 (1H), 6.24 (1H), 7.38 (1H), 7.45-7.52 (ZH), 7.60 (1H), 7.61 (1H), 7.70 (1H), 7.72 (1H) ppt.

Example 21

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(1-methyl-1 H-pyrazol-5-yl)imidazo|1,2-

B|Ipyridazin-3-yl-g-methylbenzamidon Ge) se sake with zm / -- "(7 zm /

MM

M M only 100 mg (242 μmol) 4-(6b-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo/1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 7a, was converted similarly to Example 1, using 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole , obtaining after treatment and purification 35.9 mg (31 95) of the title compound. ), 2.35 (ЗН), 2.80 (1Н), 3.35 (2Н), 413 (ЗН), 4.76 (1Н), 6.62 (1Н), 6.89 (1Н), 7 .00 (1H), 7.37 (1H), 7.51 (1H), 7.93 (1H), 7.97 (1H), 7.98 (1H), 8.30 (1H) ppt.

Example 22 3-(4-(2-Cyclopropyl-1H-imidazol-5-yl)uphenyl|-6-ethenyl-M-(3,3,3-

trifluoropropyl)imidazo|1,2-b|Ipyridazine-8-amine

HER

In U

MN MN

Fo She

SI zm / --» per zm / day tn in a pack of 55 MG (123 μMOL) b-chloro-3-(4-(2-cyclopropyl-1H-imidazol-5-yl)phenyl|-M-(3, 3,3-trifluoropropyl)imidazo(1,2-b|Ipyridazine-8-amine, which was obtained according to

Intermediate Example ba was converted analogously to Example 1 using 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane, to obtain after treatment and purification 3.2 mg (6 95) of the title compound . 1H-NMR (SOSIS): b- 0.95-1.03 (4H), 1.99 (1H), 2.56 (2H), 3.64 (2H), 5.58 (1H), 6, 07 (1Н), 6.18 (1Н), 6.76 (1Н), 7.16 (1Н), 7.68-7.74 (ЗН), 8.05 (2Н) ppt.

Example 23

M-cyclopropyl-2-methyl-4-16-(1E/2)-prop-1-en-1-ylI|-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- b|pyridazin-3-yl)ibenzamid and i

In U

MN MN

SI zm / y: zm /

М M pure 75 mg (171 μmol) 4-(6-Chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was obtained according to Intermediate Example 1ba, was converted analogously to Example 1 using (1E)-prop-1-en-1-ylboronic acid to give, after work-up and purification, 3.0 mg (4 95) of the title compound compounds. 1H-NMR (SOSIS): b- 0.63 (2H), 0.90 (2H), 1.98 (3H), 2.47-2.65 (2H), 2.54 (3H), 2.92 (1H), 3.67 (2H), 5.91 (1H), 5.98 (1H), 6.46 (1H), 6.60-6.66 (1H), 7.25 ( 1H), 7.43 (1H), 7.73 (1H), 7.90 (1H), 7.96 (IN) ppt.

Example 24

M-cyclopropyl-4-[8-(2-hydroxy-2-methylpropyl)amino|-6-(1E/2)-prop-1-en-1-ylimidazo|(1,2-b|pyridazine-3 -yl)u.2-methylbenzamidon on uFores s zm / -- -» zy zm /

M M

Chek si 75 mg (181 μmol) 4-(6-Chloro-8-((2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b|pyridazin-3-yl)"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 1 using (1E)-prop-1-en-1-ylboronic acid to give, after work-up and purification, 22 mg (29 95) of the title compound. 1H - NMR (SOSIS): 6- 0.63 (2H), 0.89 (2H), 1.43 (6H), 1.95--2.16 (ZN), 2.51 (ZN), 2, 92 (1H), 3.32 zo (2H), 4.33 (1H), 5.99 (1H), 6.07--6.14 (1H), 6.37 (1H), 6.41 ( 1H), 6.57--6.63 (1H), 7.39 (1H), 7.66--7.70 (1H), 7.84--7.87 (1H), 7.94 ( 1H) ppt.

Example 25

A-16-(2E)-But-2-en-2-yl|-8-K2-hydroxy-2-methylpropyl)aminoimidazo|1,2-BI pyridazin-3-yl)u-N-cyclopropyl-2- methylbenzamide on on

Fo day from Fri / -- -» winter /

M M

(c) M (c) M 75 mg (181 μmol) 4-16-Chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)"M -cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 1, obtaining after treatment and purification 7.0 mg (8 95) of the title compound. 1H-NMR (SOSIS): b- 0, 62 (2H), 0.88 (2H), 1.45 (6H), 1.79 (ZH), 2.11 (ZH), 2.50 (ZH), 2.91 (1H), 103.32 (2H), 5.02 (1H), 5.77 (1H), 5.97 (1H), 6.00 (1H), 6.50 (1H), 7.38 (1H), 7.70 ( 1H), 7.89 (1H), 7.91 (1H) ppt.

Example 26 3-(4-(2-Cyclopropyl-1H-imidazol-5-iluphenyl)-6-(pyridin-4-yl)-M-(3,3,3-trifluoropropyl)imidazo|1,2-b Ipyridazin-8-amine EI

In U

MN MN se ne sim" / --- te zm /

Mag ftMn tn pk mu 70 MG (157 μmol) 6-Chloro-3-(4-(2-cyclopropyl-1H-imidazol-5-yl)phenyl|-M-(3,3,3-trifluoropropyl)imidazo( 1,2-b|Ipyridazine-8-amine, which was obtained according to

Intermediate Example ba was converted analogously to Example 1, using pyridine-4-ylboronic acid, obtaining after treatment and purification 3.2 mg (4 95) of the title compound. 1H-NMR (SOSIS): b- 0.92-0.98 (4H), 1.98 (1H), 2.58 (2H), 3.32 (2H), 3.69 (2H), 6, 42 (1H), 7.15 (1), 7.72 (2H), 7.75 (1H), 7.687 (2H), 8.04 (2H), 8.65 (2H) ppm.

Example 27 6-K2E)-But-2-en-2-yl|-3-(4-(2-cyclopropyl-1H-imidazol-5-iluphenyl|-M-(3,3,3-trifluoropropyl)imidazo |1,2-b|Ipyridazin-8-amine and EI

In U

MN MN

50 MG (112 μmol) b-Chloro-3-(4-(2-cyclopropyl-1H-imidazol-5-yl)uphenyl|-M-(3) ,3,3-trifluoropropyl)imidazo|1,2-b|pyridase of yn-8-amine, which was obtained according to Intermediate Example b, was converted similarly

of Example 1, after processing and purification, 3.0 mg (5 95) of the title compound was obtained.

1H-NMR (SOSIS): b- 0.95-1.02 (4H), 1.78 (ЗН), 1.99 (1Н), 2.12 (ЗН), 2.46-2.63 (2Н ), 3.62 (2H), 5.78 (1H), 5.96 (1H), 7.16 (1H), 7.69 (2H), 7.73 (1H), 8.05 (2H) ppt

Example 28

M-cyclopropyl-4-/6-(4-fluorophenyl)-8-((3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazin-3-yl)y-2-methylbenzamide and I

In U

MN MN se dn

SI zm / -- zm /

IS

Add 50 mg (114 μmol) of 4-(6b-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was prepared according to Intermediate Example 10a, was converted analogously to Example 1 using (4-fluorophenyl)boronic acid to give, after work-up and purification, 5.4 mg (9 95) of the title compound. 1H-NMR (SOCIZ /СО300): b- 0.59 (2Н), 0.86 (2Н), 2.48 (ЗН), 2.58 (2Н), 2.86 (1Н), 3.68 (2Н), 6, 36 (1H), 7.16 (2H), 7.41 (1H), 7.74 (1H), 7.85-8.03 (4H) ppt.

Example 29 (85) 3-I(4-(2-Cyclopropyl-1H-imidazol-5-iluphenyl)-6-(pyridin-4-yl)-M-(tetrahydro-2H-pyran-2-ylmethyl)imidazo |1,2-5|Ipyridazin-8-amine in c,

MN MN se a si zm / - ii zm /

We ft Mn in 53 MG (118 μmol) (K5)-6-Chloro-3-I4-(2-cyclopropyl-1H-imidazol-4-yl)phenyl|-M-(tetrahydro-2H-pyran-2 -ylmethyl)imidazo|1,2-b|Ipyridazine-8-amine, which was obtained according to Intermediate Example 29a, was converted analogously to Example 1, using pyridine-4-ylboronic acid, obtaining after treatment and purification 6.2 mg (10 95) of the compound indicated in the title. 1H-NMR (SOSIS): b- 0.99-1.09 (4H), 1.45-2.07 (7H), 3.34-3.55 (ZH), 3.67 (1H), 4 .06 (1H), 6.26 (1H), 6.44 (1H), 7.24 (1H), 7.79 (2H), 7.83 (1H), 7.88 (2H), 8, 13 (2H), 8.74 (2H) ppt.

Intermediate Example 29a (85)-6-Chloro-3-(4-(2-cyclopropyl-1H-imidazol-4-yl)uphenyl|-M-(tetrahydro-2H-pyran-2-ylmethyl)imi dazo|1 ,2-b|Ipyridazine-v-amine and

МН about and 2

МН вый -- with M y 2

I / m u

N

105 MG (267 μmol) (K5)-6-chloro-3-iodo-M-(tetrahydro-2H-pyran-2-ylmethyl)imidazo

P,2-B|Ipyridazine-8-amine, which was obtained according to Intermediate Example 290, was converted analogously to Intermediate Example Ta to obtain, after treatment and purification, 61 mg (51 95) of the title compound.

Intermediate Example 296 (85)-6-Chloro-3-iodo-M-(tetrahydro-2H-pyran-2-ylmethyl)imidazo|1,2-5|Ipyridazin-8-amine

Ve v. uFo MN

Ffodnn sim se si i,

AND

530 mg (1.48 mmol) of 8-bromo-b-chloro-3-iodoimidazo|1,2-5|pyridazine, which was obtained according to

Intermediate Example 1c was converted analogously to Intermediate Example 16, using 1-(2A5)-tetrahydro-2H-pyran-2-yl|methanamine, obtaining after treatment and purification 214 mg (37 95) of the title compound.

Example 30 (85)-M-cyclopropyl-2-methyl-4-18-((2-methyltetrahydrofuran-2-yl)methyl)amino)-6-(pyridin-4-yl)imidazo(1,2-b| Ipyridazin-3-yl|Irenzamide no no

MN MN of the day

SI zm / ---- Y i zm /

Shield

M M another 50 mg (114 μmol) (K5)-4-(6-Chloro-8-((2-methyltetrahydrofuran-2-yl)methyl amino)imidazo(1,2-b|Ipyridazin-3-yl) y-M-cyclopropyl-2-methylbenzamide, which was obtained according to

Intermediate Example Zba was converted analogously to Example 1, using pyridine-4-ylboronic acid, to obtain after treatment and purification 12.5 mg (22 95) of the title compound. 1H-NMR (SOSIS): b- 0.64 (2H), 0.89 (2H), 1.35 (ЗН), 1.81 (1Н), 1.91-2.10 (ЗН), 2, 54 (ZH), 2.93 (IN), 3.45 (2H), 3.93 (2H), 6.10 (1H), 6.20 (1H), 6.50 (1H), 7.44 (1H), 7.79-7.84 (HN), 7.92 (1H), 7.99 (1H), 8.71 (2H) ppt.

Intermediate Example Zba (85)-4-(6-Chloro-8-(2-methyltetrahydrofuran-2-yl)methyliamino)imidazo(|1,2-b)pyridazin-3-yl)-N-cyclopropyl-2-methylbenzamide but oh MN sia sie,

M

(in)

b

150 mg (382 μmol) (K5)-6-chloro-3-iodo-M-|((2-methyltetrahydrofuran-2-yl)methylimidazo

P,2-B|Ipyridazine-8-amine, which was obtained according to Intermediate Example 300, was converted analogously to Intermediate Example la, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl)benzamide, yielding after treatment and purification 110 mg (65 Fo) of the title compound.

Intermediate Example 306 (85) 6-Chloro-3-iodo-N-(2-methyltetrahydrofuran-2-yl)methylimidazo|1,2-b|pyridazin-8-amine c

Ve yar MN

Fe; - to be

SI M p

And x si t

AND

250 mg (698 μmol) of 8-bromo-6b-chloro-3-iodoimidazo|1,2-b|pyridazine, which was obtained according to

Intermediate Example 1c was converted analogously to Intermediate Example 16, using 1-(285)-2-methyltetrahydrofuran-2-yl|methanamine, obtaining after treatment and purification 262 mg (96 95) of the title compound.

Example 31

M-cyclopropyl-2-methyl-4-|6-(pyridin-4-yl)-8-((25)-tetrahydrofuran-2-ylmethyliamino)imidazoi 1,2-vb|Ipyridazin-3-yl|benzamide o: So mn mn se dna si zm /Y ; with zm /i

We

M M total 49 mg (115 μmol) 4-(6-Chloro-8-((25)-tetrahydrofuran-2-ylmethyliamino)imidazo|1,2-B pyridazin-3-yl)-M-cyclopropyl-2- of methylbenzamide, which was obtained according to Intermediate

Example C1a was converted similarly to Example 1, using pyridine-4-ylboronic acid, with obtaining after treatment and purification 3.6 mg (6 95) of the title compound. 1H-NMR (SOSIS): 6- 0.64 (2H), 0.90 (2H), 1.75 (1H), 1.98 (2H), 2.11 (1H), 2.55 (ZH) , 2.93 (1H), 15. 3.46 (1H), 3.60 (1H), 3.82 (1H), 3.96 (1H), 4.24 (1H), 6.01 (1H ), 6.23 (1H), 6.50 (1H), 7.45 (1H), 7.83 (1H), 7.84 (2H), 7.93 (1H), 8.00 (1H ), 8.74 (2H) ppt.

Intermediate Example C1a 4-(6-Chloro-8-(25)-tetrahydrofuran-2-ylmethyliamino)imidazo|1,2-b|pyridazine-

3-yl)-M-cyclopropyl-2-methylbenzamide

With this many -

Te --e aty / s yati

M

(c) 232 MG (613 μMOL) of b-chloro-3-iodo-N-(25)-tetrahydrofuran-2-ylmethylimidazo|1,2-5|pyridazin-8-amine, which was obtained according to Intermediate Example 4B , were transformed similarly

Intermediate Example 1a, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)/ibenzamide, yielding after treatment and purification 98 mg ( 38 Fo) of the compound indicated in the title.

Example 32

M-cyclopropyl-4-(6-(4-fluorophenyl)-8-(2-hydroxy-2-methylpropyl)amino)imidazo|1,2-b|Ipyridazin-3-ylbenzenecarbothioamidon

МН M z, M zm / --йфпЕ M

IS

IS

M u u 33 mg (82 μmol) / 4-6-(4-fluorophenyl)-8-(2-hydroxy-2-methylpropyl)amino|imidazo

P,2-Shipyridazin-3-yl)/benzaldehyde, which was obtained according to Intermediate Example 32a, was converted similarly to Example 13 to obtain after treatment and purification 3.3 mg (8 95) 5 of the title compound. 1H-NMR (0M5O-ab): 6- 0.75-0.88 (4H), 1.18 (6H), 3.40 (2H), 3.47 (1H), 4.78 (1H), 6.81 (1H), 6.95 (1H), 7.35 (2H), 7.84 (2H), 8.07 (1H), 8.11 (2H), 8.26 (2H), 10 ,16 (1H) ppt.

Intermediate Example 32a 4-(6-(4-Fluorophenyl)-8-K2-hydroxy-2-methylpropyl)aminoimidazol|1,2-b|pyridazin-3-yl)benzaldehyde

OH on ks days zm 7 --g zm Y and E c) Y 48 MG (107 μmol) 1-(13-I4-(1,3-dioxolan-2-yl)phenyl|-6-(4-fluorophenyl) imidazo

P,2-VIpyridazin-8-ylamino)-2-methylpropan-2-ol, which was obtained according to Intermediate

Example 3206 was converted analogously to Intermediate Example 13a, obtaining after treatment and purification 34.6 mg (76 95) of the title compound.

Intermediate Example 326 1-(13-I4-(1,3-Dioxolan-2-iluphenyl|-6-(4-fluorophenyl)imidazo|1,2-b|pyridazin-8-yl)amino)-2-methylpropan- 2-ol on on

Fo la

SI zm / --x zm /

IS

9 ef 100 mg (257 μmol) 1-((b-chloro-3-I(4-(1,3-dioxolan-2-yl/uphenylimidazo/1,2-b|Ipyridazin-8- ilyamino)-2- methylpropan-2-ol, which was obtained according to Intermediate Example 32c, was converted analogously to Example 1 using (4-fluorophenyl)boronic acid, obtaining after treatment and purification 50.0 mg (43 95) of the title compound.

Intermediate Example 32c 1-(13-I4-(1,3-Dioxolan-2-iluphenyl|-6-(4-fluorophenyl)imidazo|1,2-b|pyridazin-8-yl)amino)-2-methylpropan- 2-ol he and: more

MN se sim / sys s zani

AND

09 2.65 g (7.2 mmol) of 1-((b-chloro-3-iodoimidazo|1,2-b|pyridazin-8-yl)amino|-2-methylpropan-2-ol, which was obtained according to Intermediate Example 10, converted similarly to Intermediate

Example 1a, using 2-I4-(1,3-dioxolan-2-yl)phenyl|)|-4,4,5,5-tetramethyl-1,3,2-dioxaborolane with the yield after treatment and purification of 1.36 g (48 95) of the compound specified in the title.

Example 33

M-cyclopropyl-2H-methyl-4-(6-(1-methyl-1H-pyrazol-5-yl)-8-(2H)-tetrahydrofuran-2-ylmethyliamino)imidazo|1,2-b|pyridazine -3-yl|benzamide I do not

MN MN

Fo la

SI zm / » y: zm /

H

MM

M M

(c) (c) (o b b 63 mg (148 μmol) 4-(6-chloro-8-(2A)-tetrahydrofuran-2-ylmethyliamino)imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 33 was converted similarly to Example 1, using 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, with the result that after treatment and purification 10 .6 mg (14 Fo) of the title compound. 1H-NMR (SOSIS): 6- 0.64 (2H), 0.89 (2H), 1.72 (1H), 1.97 (2H), 2.09 (1H), 2.50 (ZH) , 2.92 (1H), 3.40 (1H), 3.53 (1H), 3.81 (1H), 3.95 (1H), 4.17 (ЗН), 4.21 (1H), 6.05 (1H), 6.17 (1H), 6.30 (1H), 6.63 (1H), 7.39 (1H), 7.52 (1H), 7.76 (1H), 7.83 (1H), 7.88 (1H) ppt.

Intermediate Example ZZa 4-(6-Chloro-8-((2НА)-tetrahydrofuran-2-ylmethylamino)imidazo|1,2-b|pyridazin-3-y|)-M-cyclopropyl-2-methylbenzamide not about MH

MN sons and father

M also 247 mg (652 μmol) b-chloro-3-iodo-M-(2HA)-tetrahydrofuran-2-ylmethylimidazo

P,2-VIpyridazine-8-amine, which was obtained according to Intermediate Example 506, was converted analogously to Intermediate Example la, using N-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl)/ibenzamide to give, after treatment and purification, 127 mg (46 Fo) of the title compound.

Example 34

M-cyclopropyl-2-methyl-4-(6-(1-methyl-1H-pyrazol-5-yl)-8-((25)-tetrahydrofuran-2-ylmethyliamino)imidazo|1,2-b|pyridazine -3-yl|benzamide

S S kn kn

Photo 2

SI zm / » y: zm /

H

MM

49 MG (115 μmol) 4-(6-chloro-8-((25)-tetrahydrofuran-2-ylmethyl|amino)imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 31a was converted similarly to Example 1, using 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, with the result that after treatment and purification 8.5 mg (15 Fo) of the title compound. 1H-NMR (SOSIS): 6- 0.64 (2H), 0.89 (2H), 1.72 (1H), 1.97 (2H), 2.09 (1H), 2.50 (ZH) , 2.92 (1H), 3.40 (1H), 3.53 (1H), 3.81 (1H), 3.95 (1H), 4.17 (ЗН), 4.21 (1H), 6.05 (1H), 6.17 (1H), 6.30 (1H), 6.63 (1H), 7.39 (1H), 7.52 (1H), 7.76 (1H), 7.83 (1H), 7.88 (1H) ppt.

Example 35

M-cyclopropyl-2-methyl-4-I6-(pyridin-4-yl)-8-((2A)-tetrahydrofuran-2-ylmethyliamino)imidazoi 1,2-bb|Ipyridazin-3-yl|benzamide I

MN MN

Fo dn si zm / -- i yo: zm /

Magician

M M

Chek also 63 mg (148 μmol) 4-(6-chloro-8--(2A)-tetrahydrofuran-2-ylmethyliamino)imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 33Za was converted analogously to Example 1, using pyridine-4-ylboronic acid, obtaining after treatment and purification 4.2 mg (6 95) of the title compound. 1H-NMR (SOSIS): 6- 0.64 (2H), 0.90 (2H), 1.75 (1H), 1.98 (2H), 2.11 (1H), 2.55 (ZH) , 2.93 (1H), 3.46 (1H), 3.59 (1H), 3.82 (1H), 3.96 (1H), 4.24 (1H), 6.02 (1H), 6.20 (1H), 6.49 (1H), 7.45 (1H), 7.83 (1H), 7.84 (2H), 7.93 (1H), 8.01 (1H), 8.73 (2H) ppt.

Example 36 (85)-M-cyclopropyl-4-8-((1,4-dioxan-2-ylmethyl)amino|-6-(pyridin-4-yl)imidazo

P,2-Shipyridazin-3-yl)y-2-methylbenzamide o o

MN MN

Fo Dn sim" / ku zm /

We

M M si 88 mg (199 μmol) (K5)-4-(6b-chloro-8-|(1,4-dioxan-2-ylmethyl)amino|imidazo|1,2-b|Ipyridazin-3-yl )"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example Zba, was converted analogously to Example 1 using pyridine-4-ylboronic acid, 3 obtaining after treatment and purification 2.9 mg (C 95) of the title compound. 1H-NMR (SOSIS): b- 0.62 (2H), 0.88 (2H), 2.52 (3H), 2.90 (1H), 3.36-4.01 (9H), 6, 06 (1H), 6.23 (1H), 6.46 (1H), 7.44 (1H), 7.80 (1H), 7.84 (2H), 7.90 (1H), 7.98 (1H), 8.70 (2H) ppt.

Intermediate Example Zba

(85)-4-6-Chloro-8-(1,4-dioxan-2-ylmethyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide ( in the village of MN

Fo

MN seni 4 si i

A total of 200 mg (507 μmol) of (K5)-6-chloro-N-(1,4-dioxan-2-ylmethyl)-3-iodoimidazoi|1,2-B) pyridazine-8-amine, which was obtained according to Intermediate Example 36p was converted analogously to Intermediate Example 1a using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, to obtain after treatment and purification of 93.6 mg (42 Fo) of the title compound.

Intermediate Example 36B (85)-6-Chloro-M-(1,4-dioxan-2-ylmethyl)-3-iodoimidazo(1,2-b|Ipyridazin-8-amine o

Ve v

Fo - z" MN

FU. i-f cm uFo

First, 500 mg (1.40 mmol) of 8-bromo-b-chloro-3-iodoimidazo|1,2-5|pyridazine, which was obtained according to

Intermediate Example 1c was converted analogously to Intermediate Example 16, using 1-(2А85)-1,4-dioxan-2-yl|methanamine, obtaining after treatment and purification 520 mg (94 Fo) of the title compound.

Example 37. -3-yl)ubenzamid in c

MN MN

Fo day sim" / pi: zm /

Magician

N N

Shh Shh 63 MG (1433 μmol) (85)-4-(6-chloro-8-Ktetrahydro-2H-pyran-2-ylmethyl)amino|imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 37a was converted analogously to Example 1, using pyridine-4-ylboronic acid, obtaining after treatment and purification 4.0 mg (5 95) of the title compound. 1H-NMR (SOSIS): b- 0.63 (2H), 0.688 (2H), 1.40-2.03 (6H), 2.53 (ZH), 2.91 (1H), 3.33- 3.55 (ZH), 3.66(1H), 4.05(1H), 6.18 (1H), 6.43 (1H), 6.47 (1H), 7.44 (1H), 7.680 (1H), 7.83 (2H), 7.91 (1H), 7.98 (1H), 8.70 (2H) ppt.

Intermediate Example 37a (85)-4-6-Chloro-8-((tetrahydro-2H-pyran-2-ylmethyl)amino|imidazo|1,2-p)pyridazin-3-yl)y"-M-cyclopropyl- 2-methylbenzamide in the city of MN

Fo

MN sy 4 s with

b

100 mg o (255 μmol) 6b-chloro-3-iodo-M-(tetrahydro-2H-pyran-2-ylmethyl)imidazo|1,2-B) pyridazine-8-amine, which was obtained according to Intermediate Example 29p, was converted analogously to Intermediate Example 1a, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)/ibenzamide, to give after work-up and purification 68 mg (61 Fo) of the title compound.

Example 38

M-cyclopropyl-4-[6-(2-(hydroxymethyl)phenyl|-8-K2-methoxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamide o7 07

Fo not M

SI zm / -- 4ja- zm / on

M M

(c) (c) (o b b 62 mg (145 μmol) 4-[6-chloro-8-(2-methoxy-2-methylpropyl)amino|imidazo|(1,2-p|Ipyridazin-3-yl )"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 17a, was converted analogously to Example 1, using (2-(hydroxymethyl)phenyl|boronic acid, obtaining after treatment and purification 24.8 mg (33 95) of the specified in the title of the compound. 1H-NMR (SOSIS): 6- 0.58 (2H), 0.84 (2H), 1.31 (6H), 2.47 (3H), 2.87 (1H), 3, 28 (ZH), 3.34 (2H), 4.13 (1H), 4.38 (2H), 6.19 (1H), 6.21 (1H), 6.25 (1H), 7.36 (1H), 7.42-7.49 (H), 7.59 (1H), 7.61 (1H), 7.70 (1H), 7.72 (1H) mp.

Example 39

M-cyclopropyl-4-18-((2-methoxy-2-methylpropyl)amino1|-6-(1-methyl-1H-pyrazol-5-yl)imidazo|1,2-b|Ipyridazin-3-yl )y.2-methylbenzamide o7 07 se la s zm / --- zy /

XX

MM

M M pure 70 mg (164 μmol) 4-(6b-chloro-8-(2-methoxy-2-methylpropyl)amino|midazol(1,2-b|pyridazin-3-yl)"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 17a, was converted analogously to Example 1, using 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole , after treatment and purification, 30 mg (37 Fo) of the title compound was obtained. 50 (ZN), 2.91 (1H), 3.27 (ZN), 3.32 (2H), 4.16 (ZN), 6.10 (1H), 6.17 (1H), 6.25 (1H), 6.62 (1H), 7.38 (1H), 7.51 (1H), 7.76 (1H), 7.83 (1H), 7.87 (1H) ppt.

Example 40

M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-vinylimidazo|1,2-B pyridazin-3-yl)y-2-methylbenzamidon se a) si zm Y zm Y

M M another 100 mg (242 μmol) of 4-16-Chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2- methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 1, using 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane, obtaining after treatment and purification 13 mg (12 95) of the title compound. 1H-NMR (SOSIS): 6- 0.63 (2H), 0.89 (2H), 1.43 (6H), 2.52 (3H), 2.92 (1H), 3 .35 (2H), 5.56 (1H), 5.97 (1H), 6.07 (1H), 6.22 (1H), 6.37 (1H), 6.73 (1H), 7, 40 (1H), 7.71 (1H), 7.50 (1H), 7.94 (1H) ppt.

Example 41

M-cyclopropyl-2-methyl-4-18-(3,3,3-trifluoropropyl)amino)|-6-vinylimidazo

P,2-Shipyridazine-3-ilubenzamide

E E

E E

In U

MN MN

Fo Fe sim 7 ka a 4

M M another 100 mg (228 μmol) 4-(6-Chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was obtained according to Intermediate Example 10a, was converted analogously to Example 1 using 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane, yielding after work-up and purification 11.4 mg (10 vol) of the title compound. 1H-NMR (SOSIS): 6- 0.62 (2H), 0.89 (2H), 2.52 (3H), 2.56 (2H), 2.92 ( 1H), 3.69 (2H), 5.60 (1H), 5.92 (1H), 5.95 (1H), 6.09 (1H), 6.20 (1H), 6.77 (1H ), 7.42 (1H), 7.75 (1H), 7.91 (1H), 7.95 (1H) ppt.

Example 42

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(1,2,3,6-tetrahydropyridin-4-yl)imidazo|1,2-b|pyridazine-3 -il)u.2-methylbenzamidon on se dn satyny 7 zy 7 ny

M M only 50 mg (121 μmol) 4-(6-Chloro-8-|((2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b|pyridazin-3-yl-N-cyclopropyl -2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 1, using 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3 ,6-tetrahydropyridine, after treatment and purification yielded 10.5 mg (18 95) of the title compound. ,16 (6H), 2.37 (ZH), 2.61 (2H), 2.80 (1H), 3.05 (2H), 3.91 (2H), 3.56 (1H), 6, 54 (1H), 6.66-6.74 (2H), 7.35 (1H), 7.97 (1H), 8.03 (1H), 8.04 (1H), 8.26 (IN) , 8.28 (1H) ppt.

Example 43 4-(6-"Cyclohex-1-en-1-yl)-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(|1,2-BI pyridazin-3-yl)"- M-cyclopropylbenzenecarbothioamidon it is not chn

MN M z. M z, -- - M

M

7 in U 20, mg (53 μmol) 4-16-(cyclohex-1-en-1-yl)-8-(2-hydroxy-2-methylpropyl)amino|imidazo

P,2-S-Pyridazin-3-yl/benzaldehyde, which was obtained according to Intermediate Example 43a, was converted similarly to Example 13 to obtain, after treatment and purification, 3.2 mg (13 O) of the title compound. 1H-NMR (0M5O-avb): 0- 0.75-0.85 (4H), 1.15 (6H), 1.61 (2H), 1.71 (2H), 2.22 (2H), 2.52 (2H), 103.13 (2H), 3.49 (1H), 4.77 (1H), 6.51 (1H), 6.63 (1H), 6.68 (1H), 7 .83 (2H), 8.01 (1H), 8.21 (2H), 10.12 (1H) ppt.

Intermediate Example 4Za 4-(6-"Cyclohex-1-en-1-yl)-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(|1,2-BI pyridazine-3-ylbenzaldehyde and one

From ss with / -- zm 58 o 97 mg (223 μmol) 1-(16-(cyclohex-1-en-1-yl)-3-I(4-(1,3-dioxolan-2-yl)phenyl) imidazo

P,2-VIpyridazin-8-ylamino)-2-methylpropan-2-ol, which was obtained according to Intermediate

Example 430 was converted analogously to Intermediate Example 13a, obtaining after treatment and purification 24 mg (25 95) of the title compound.

Intermediate Example 43p 1-(16-"Cyclohex-1-en-1-yl)-3-(4-(1,3-dioxolan-2-yl)phenylimidazo|1,2-BI pyridazine-8-ylylamino) -2-methylpropan-2-ol on Ge)

Fo dn M

SI zm ) --x zm ) o ef 100 mg (257 μmol) 1-((b-chloro-3-I(4-(1,3-dioxolan-2-yl)uphenylimidazo(1,2-b|Ipyridazine -8-yl)amino)-2-methylpropan-2-ol, which was obtained according to Intermediate Example 32c, was converted analogously to Example 1, using cyclohex-1-en-1-ylboronic acid, obtaining after treatment and purification 97 mg ( 87 95) of the compound specified in the title.

Example 44

M-cyclopropyl-4-/6-(2-(hydroxymethyl)phenyl)|-8-(3,3,3-trifluoropropyl)amino imidazo|1,2-b|Ipyridazin-3-ylbenzenecarbothioamide

E sa a

IS

MN

MN M sot A gu. / » change

M

) he in U 72.3 mg (164 μmol) 4-(6-(2-(hydroxymethyl)phenyl|-8-(3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazin-3-yl)/benzaldehyde, which was obtained according to Intermediate Example 44a, was converted similarly to Example 13, obtaining after treatment and purification 6.6 mg (7 9) of the title compound. 1H-NMR (SOSIS): b- 0.76 (2H), 1.00 (2H), 2.58 (2H), 3.37 (1H), 3.72 (2H), 3.96 (1H) , 4.40 (2H), 6.16 (1H), 6.25 (1H), 7.46-7.51 (ZH), 7.59 (1H), 7.76 (1H), 7.77 (2H), 7.84 (2H), 7.89 (1H) ppt.

Intermediate Example 44a 4-(6-(2-(Hydroxymethyl)phenyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-B)pyridazine-3-ylbenzaldehyde

IS

Well

E U

MN MN sai - a 28 zim 4 --- ; r on on b s 52 mg (107 μmol) /(2-13-I4-(1,3-dioxolan-2-yl/uphenyl|-8-KZ3,3,3-trifluoropropyl)amino)imidazo|1,2 -b|Ipyridazine-b-iluphenyl)umethanol, which was obtained according to Intermediate Example 44p, was converted similarly to Intermediate Example 13a, obtaining after treatment and purification 72.3 mg (76 95) of the title compound.

Intermediate Example 44p (2-13-I4-(1,3-Dioxolan-2-yl)phenyl|-8-KZ,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazine-b-iluphenyl)methanol

E E

E E

In the RU

MN MN

Fola sim" / TU-k zm / on ef b 100 mg (242 μmol) b-chloro-3-(4-(1,3-dioxolan-2-yl)uphenyl|-M-(3,3,3 -trifluoropropyl)imidazo

P,2-B|Ipyridazine-8-amine, which was obtained according to Intermediate Example 44c, was converted analogously to Example 1, using (|2-(hydroxymethyl)uphenyl|boronic acid), to obtain after treatment and purification 52 mg (44 95) of the title compound.

Intermediate Example 44c b-Chloro-3-I4-(1,3-dioxolan-2-iluphenyl|-M-(3,3,3-trifluoropropyl)imidazoi|1,2-B)pyridazin-8-amine; and

R MN

And that's it

MN se Ch-x sim" / sashe sya s shchi,

I ef 800 mg (2.05 mmol) b-chloro-3-iodo-M-(3,3,3-trifluoropropyl)imidazo|1,2-b|Ipyridazin-8-amine, which was obtained according to Intermediate Example 6p , converted similarly to Intermediate

Example 1a, using 2-I4-(1,3-dioxolan-2-yl)phenyl|)|-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, with obtaining after treatment and purification 332 mg (35 95) of the title compound.

Example 45

M-cyclopropyl-4-(6-(1-methyl-1H-pyrazol-5-yl)-8-((3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3- ilybenzenecarbothioamide

E and sa

IS

MN

MN M

In the afternoon and F

CHI, - whales and M Um

M

5 (o) o b 27 mg (65 μmol) 4-(6-(1-methyl-1H-pyrazol-5-yl)-8-(3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazin-3-yl)/benzaldehyde, which was obtained according to Intermediate Example 45a, was converted similarly to Example 13, obtaining after treatment and purification 1.8 mg (5 95) of the title compound. 1H-NMR (SOSIS): b- 0.82 (2H), 1.07 (2H), 2.59 (2H), 3.42 (1H), 3.73 (2H), 4.19 (3H) , 6.08 (1H), 6.29 (1H), 6.66 (1H), 7.56 (1H), 7.64 (1H), 7.84 (2H), 7.85 (1H), 8.07 (2H) ppt.

Intermediate Example 45a 4-(6-(1-Methyl-1H-pyrazol-5-yl)-8-((3,3,3-trifluoropropyl)amino|imidazoi|1,2-B pyridazine-3-ylbenzaldehyde)

IS

Well

And a

MN MN and ex) - 2-2 M

Kz z / » /e zm Y

MM M

(6) p (c) - about 73 MG (159 μMOL) 3-I(4-(1,3-dioxolan-2-yl)phenyl|-6-(1-methyl-1H-pyrazol-5-yl) )-M-(3,3,3-trifluoropropyl)imidazoi|1,2-BI pyridazine-8-amine, which was obtained according to Intermediate Example 4506, was converted analogously to Intermediate Example 13a to obtain after treatment and purification 27 mg (41 965 ) of the title compound.

Intermediate Example 4565 3-I(4-(1,3-Dioxolan-2-yl)uphenyl/|-6-(1-methyl-1 H-pyrazol-5-yl)-M-(3,3,3- trifluoropropyl)imidazo|1,2-b|pyridazin-8-amine

And I

RU U

MN MN se dn M sim u im u

H

MM b b 100 mg o (242 μmol) 6b-chloro-3-I4-(1,3-dioxolan-2-yl)phenyl|-M-(3,3,3-trifluoropropyl)imidazo|(1,2- b|Ipyridazine-8-amine, which was obtained according to Intermediate Example 44c, was converted analogously to Example 1, using 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl )-1H-pyrazole, with treatment and purification yielding 73 mg (66 95) of the title compound.

Example 46

M-cyclopropyl-4-(6-3-(hydroxymethyl)phenyl)|-8-(3,3,3-trifluoropropyl)amino imidazo|1,2-b|Ipyridazin-3-ylbenzenecarbothioamide

Eh sa sa

IS

MN

MN M

Afternoon with F

CHI -- change

391 mg (89 μmol) /-4-16-(3-(hydroxymethyl)phenyl)-8-((3,3,3-trifluoropropyl)amino)imidazo|1, 2-b|Ipyridazin-3-yl)ubenzaldehyde, which was obtained according to Intermediate Example 46ba, was converted analogously to Example 13 to obtain, after work-up and purification, 2.0 mg (4 o) of the title compound. 1H-NMR (SOSIS): b- 0.83 (2H), 1.07 (2H), 2.56 (2H), 3.43 (1H), 3.68 (2H), 4.82 (2H), 6.00 (1H) , 6.40 (1H), 7.50 (2H), 7.71 (1H), 7.79-7.90 (5H), 8.15 (2H) ppt.

Intermediate Example 4ba 4-(6-3-Hydroxymethyl)phenyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-B) pyridazine-3-ylbenzaldehyde pi v. be U chn MN a sa what ----- what r new in) no R

A about 167 mg (μmol) (3-73-I4-(1,3-dioxolan-2-iluphenyl)|-8-((3,3,3-trifluoropropyl)amino|imidazo

P,2-VIpyridazine-6-iluphenyl)methanol, which was obtained according to Intermediate Example 466, was converted similarly to Intermediate Example 13Za, obtaining after treatment and purification 39.1 mg (37 95) of the title compound.

Intermediate Example 46p (3-13-I4-(1,3-Dioxolan-2-yl)phenyl|-8-KZ,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazine-b-iluphenyl)methanol

And I

In U

MH MH se a) sieves / TCH-x change 07 59 100 mg (242 μmol) b-chloro-3-(4-(1,3-dioxolan-2-iluphenyl|-M-(3,3,3- trifluoropropyl)imidazo

β,2-bipyridazine-8-amine, which was obtained according to Intermediate Example 44c, was converted analogously to Example 1 using (|3-(hydroxymethyluphenyl)|Iboronic acid, obtaining after treatment and purification 83.5 mg (71 95) specified in the title of the compound.

Example 47

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-4-yl)imidazo

P,2-Shipyridazin-3-yl benzenecarbothioamid on ve ne chi

MN M afternoon ss with.

M. Ma

M

Moshe 48 mg (124 μmol) 4-18-K2-hydroxy-2-methylpropyl)amino |-6-(pyridin-4-yl)imidazo

P,2-S-Pyridazin-3-yl/benzaldehyde, which was obtained according to Intermediate Example 47a, was converted similarly to Example 13 to obtain, after treatment and purification, 4.7 mg (6 O) of the title compound. 1H-NMR (0M50-46): b- 0.76-0.88 (4H), 1.18 (6H), 3.38-3.52 (ZH), 4.79 (1H), 6.93 (1H), 7.09 (1H), 7.86 (2H), 8.04 (2H), 8.12 (1H), 8.27 (2H), 8.73 (2H), 10.16 ( 1H) ppt.

Intermediate Example 47a 4-i8-K2-Hydroxy-2-methylpropyl)amino|-6-(pyridin-4-yl)imidazo|(1,2-b|pyridazine-

Z-ilybenzaldehyde in Hesa F - 2 g" What - - what

Ma M. same ef o 69 MG (160 μMOL) 1-(13-I4-(1,3-dioxolan-2-yl)phenyl|-6-(pyridin-4-yl)imidazo|1,2-b| Ipyridazin-8-ylamino)-2-methylpropan-2-ol, which was obtained according to Intermediate Example 476, was converted analogously to Intermediate Example 13Za to obtain after treatment and purification 51.5 mg (83 95) of the title compound.

Intermediate Example 47p 1-(13-I4-(1,3-Dioxolan-2-yl)phenyl)|-6-(pyridin-4-yl)imidazo|1,2-b|pyridazin-8-yl)amino) -2-methylpropan-2-ol

Ge) he se la)

SI zm / -- 6 I i zm /

Ma of, of 200 mg (514 μmol) 1-((b-chloro-3-(4-(1,3-dioxolan-2-yl)phenylimidazo|(1,2-b|Ipyridazin-8- ilyamino)- 2-methylpropan-2-ol, which was obtained according to Intermediate Example 32c, was converted analogously to Example 1 using pyridine-4-ylboronic acid, 3 yielding after treatment and purification 51.5 mg (23 95) of the title compound.

Example 48

M-cyclopropyl-4-(6-cyclopropyl-8-((3,3,3-trifluoropropyl)amino|imidazoi|1,2-B pyridazin-3-yl)-2-methylbenzamide

Y I be U

МН МН ее дн

Ua 4 » winter i

M M

Cheeks

A solution of 31 mg (72 μmol) of M-cyclopropyl-2-methyl-4-(8-(3,3,3-trifluoropropyl)amino|-b-vinylimidazo|(1,2-b|pyridazine-3-ylibenzamide), which obtained according to Example 41 in 3.5 ml of tetrahydrofuran, cooled to 3 "C, 5 ml of a solution of diazomethane in diethyl ether was added after 0.81 mg of palladium(I!) diacetate, and the mixture was stirred for an hour.

The solvents were removed and the residue was purified by chromatography to give 5.8 mg (18 95) of the title compound. 1H-NMR (SOSIS): b- 0.63 (2H), 0.89 (2H), 1.00-1.11 (4H), 2.00 (1H), 2.53 (ZH), 2, 47-2.61 (2H), 2.92 (1H), 3.65 (2H), 5.78 (1H), 5.91 (1H), 5.93 (1H), 7.41 (1H) , 7.73 (1H), 7.91 (1H), 7.92 (1H) ppt.

Example 49

M-cyclopropyl-4-(6-(4-fluorophenyl)-8-(2-hydroxy-2-methylpropyl)amino)imidazo|(1,2-b|Ipyridazin-3-yl-3-methoxybenzamidone)

Fo a) si zm J o-- z J o--

IS

M M

Chek Chek 75 mg (174 μmol) 4-(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b|pyridazin-3-yl)"UM-cyclopropyl-3- methoxybenzamide, which was prepared according to Intermediate Example 485a, was converted analogously to Example 1 using (4-fluorophenyl)boronic acid to give, after work-up and purification, 18.5 mg (22 95) of the title compound. 1H-NMR (0M50O-ab ): b- 0.57 (2Н), 0.69 (2Н), 1.19 (6Н), 2.85 (1Н), 3.39 (2Н), 3.89 (ЗН), 4.78 ( 1), 6.77 (1H), 6.87 (1H), 7.31 (2H), 7.54 (1H), 7.56 (1H), 7.687 (1H), 8.03 (2H), 8.25 (1H), 8.51 (1H) ppt.

Example 49a 4-i6-Chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo/1,2-b|Ipyridazin-3-yl-

M-cyclopropyl-3-methoxybenzamide on

Ge) and everything

MN with 2nd ---k cm o-. with more

I n (c) in 1.0 g (2.73 mmol) of 1-(6-Chloro-3-iodoimidazo|1,2-b|pyridazin-8-yl)amino|-2-methylpropan-2-ol, which was obtained according to Intermediate Example 10, was converted similarly to Intermediate

of Example 1a, using |4-(cyclopropylcarbamoyl)-2-methoxyphenyl|boronic acid, which was obtained according to Intermediate Example 496, to obtain after treatment and purification 741 mg (60 Fo) of the title compound.

Example 496

І4-«(Cyclopropylcarbamoyl)-2-methoxyphenyl|boronic acid (c) (c) he i --k nov nov on, on,

A suspension of 3.0 g (15.3 mmol) of 4-(dihydroxyboryl)-3-methoxybenzoic acid, 874 mg of cyclopropanamine, and 3.5 g of M-13-(dimethylamino)propyl|-methylcarbodiimide in 93 mL of dichloromethane was stirred overnight at 23 "C.

Water was added and the mixture was extracted with dichloromethane. The organic layer was washed with brine and dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to give 2.60 g (72 Fo) of the title compound.

Example 50

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(1-methyl-1 H-pyrazol-5-yl)imidazo|1,2-

B|Ipyridazin-3-yl-Z-methoxybenzamide on on

Fo la) si zm J o-. uz zy J o-.

MM

M M

(c) (c) h b b 75 mg (174 μmol) 4-(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b|pyridazin-3-yl) "M-cyclopropyl-3-methoxybenzamide, which was obtained according to Intermediate Example 4985a, was converted analogously to Example 1, using 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)-1H-pyrazole, with treatment and purification yielding 14.8 mg (18 Fo) of the title compound. 1H-NMR (0M5O-46): 6- 0.57 (2H), 0.69 (2H) , 1.17 (6Н), 2.83 (IN), 3.35 (2Н), 3.85 (ЗН), 4.01 (ЗН), 4.77 (1Н), 6.59 (1Н), 6.85 (1H), 6.95 (1H), 7.47 (1H), 7.51 (1H), 7.53 (1H), 7.81 (1H), 8.03 (1H), 8 .49 (1H) ppt.

Example 51

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(phenylsulfanyl)imidazo|1,2-b|pyridazin-3-yl/y-3-methoxybenzamide (A) and

M-cyclopropyl-z-hydroxy-4-(8-K2-hydroxy-2-methylpropyl)amino|-6-(phenylsulfanyl)imidazo|1,2-5|pyridazine-3-ilubenzamide (B)

he he he u/Fo oo eo si ---k you N you (in) (in no , ,

M M M sho 47 in M

27.9 mg of sodium hydride (60 95) was added to a solution of 76.9 mg of benzene thiol in 1.0 ml of dimethylsulfoxide, and the mixture was stirred at 23 "С for an hour. Then 50 mg (116

MKMOL) of 4-(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl-3-methoxybenzamide, which was obtained according to Intermediate Example 49a, and the mixture was heated at 120 "C using microwave irradiation for an hour.

Water was added and the mixture was extracted with dichloromethane and methanol. The organic layer was washed with brine and dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to give 8.0 mg (18 95) of the title compound A and 15.3 mg (27 95) of the title compound B. 1H-NMR (0M5O-46) of A: b - 0.56 (2Н), 0.69 (2Н), 1.10 (6Н), 2.82 (1Н), 3.19 (2Н), 3.27 (ЗН), 4.70 (1Н), 6.19 (1H), 6.97 (1H), 7.22 (1H), 7.41-7.47 (4H), 7.53-7.58 (2H), 7.85 (1H), 7.86 (1H), 8.44 (IN) ppt. 1H-NMR (0M5O-46) oi B: 6b- 0.54 (2H), 0.66 (2H), 1.10 (6H), 2.80 (1H), 3.18 (2H), 4, 70 (1H), 6.17 (1H), 6.98 (1H), 7.04 (1H), 7.33 (1H), 7.42-7.48 (ZH), 7.55-7, 61 (2H), 7.87 (1H), 7.95 (1H), 8.33 (1H), 10.13 (1H) ppt.

Example 52

M-cyclopropyl-4-/6-(4-fluorophenyl)-8-((3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazin-3-yl-3-methoxybenzamide and schi

In U

MN MN is not

SI zm / --2 zm / ,9 E ,/

M M

(c) (c) h b b5 mg (143 μmol) 4-(6b-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo/1,2-b|Ipyridazin-3-yl) "M-cyclopropyl-3-methoxybenzamide, which was obtained according to Intermediate Example 52a, was converted analogously to Example 1 using (4-fluorophenyl)boronic acid, obtaining after treatment and purification 14.3 mg (18 95) of the title compound. 1H-NMR (SOSIS): b- 0.66 (2H), 0.91 (2H), 2.59 (2H), 2.95 (1H), 3.75 (2H), 3.97 (3H) , 6.00 (1H), 6.32 (1H), 6.39 (1H), 7.17 (2H), 7.33 (1H), 7.58 (1H), 7.90 (2H), 8.01 (1H), 8.37 (1H) ppt.

Intermediate Example 52a 4-(6-Chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)y-

M-cyclopropyl-3-methoxybenzamide c.

IN

E.I MN be o M

MH CHI,

SI M si zy 7

M

(c) from b

484 mg (1.24 mmol) of b-chloro-33-iodo-M-(3,3,3-trifluoropropyl)imidazo(1,2-b|Ipyridazin-8-amine, which was obtained according to Intermediate Example 6p, was converted similar to Intermediate

of Example 1a, using |4-(cyclopropylcarbamoyl)-2-methoxyphenyl|boronic acid, which was obtained according to Intermediate Example 496, to obtain after treatment and purification 163 mg (29 Fo) of the title compound.

Example 53

M-cyclopropyl-3-methoxy-4-16-(1-methyl-1 H-pyrazol-5-yl)-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b| Pyridazin-3-yl)ibenzamid p I

In the RU

MN MN of the day

SI zm / -- y: zm /

H

/o MM, /o

М M pure 65 mg (143 μmol) 4-6-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl- C-Methoxybenzamide, which was obtained according to Intermediate Example 52a, was converted analogously to Example 1, using 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H -pyrazole, after processing and purification, 3.6 mg (5 o) of the title compound was obtained. ), 2.94 (1H), 3.72 (2H), 3.94 (ЗН), 4.11 (ЗН), 6.04 (1Н), 6.27 (1Н), 6.31 (1Н) , 6.64 (1H), 7.27 (1H), 7.53 (1H), 7.58 (1H), 7.95(1H), 8.13 (1H) ppt.

Example 54

M-cyclopropyl-4-/6-(2-(hydroxymethyl)phenyl)|-8-(3,3,3-trifluoropropyl)amino imidazo|(1,2-b|Ipyridazin-3-yl-3-methoxybenzamide and EY

In U

MN MN

Fo nem sim 0-05 zni o-- on

M M

(c) (c) h b b 50 mg (110 μmol) 4-(6-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl) "M-cyclopropyl-3-methoxybenzamide, which was obtained according to Intermediate Example 52a, was converted analogously to Example 1, using (2-(hydroxymethyl)phenyl|ronic acid), obtaining after treatment and purification 11.8 mg (18 95) specified in of the title compound. 1H-NMR (SOSIS): 6- 0.60 (2H), 0.85 (2H), 2.58 (2H), 2.88 (1H), 3.73 (2H), 3.90 (ЗН), 4.39 (2Н), 512 (1Н), 6.13 (1Н), 6.24 (1Н), 6.34 (1Н), 7.22 (1Н), 7.43-7, 49 (ZH), 7.55 (1H), 7.58 (1H), 7.79 (1H), 7.84 (1H) ppt.

Example 55

M-cyclopropyl-4-16-(2-methoxyphenyl)sulfanyl|)|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2 -methylbenzamide

Yi B

In U

МН МН somewhere I'm fed up /o o o o o o

50 mg (114 μmol) 4-(6b-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 10a, was converted analogously to Example 51 using 2-methoxybenzenethiol to give after work-up and purification 9.2 mg (14 95) of the title compound. 2H), 0.88 (2H), 2.36 (ZH), 2.47 (2H), 2.89 (1H), 3.52 (2H), 3.77 (ZH), 5.88 (1H ), 6.01 (1H), 6.28 (1H), 6.97-7.07 (2H), 7.16 (1H), 7.48 (1H), 7.57-7.65 (ЗН ), 7.67 (1H) ppt.

Example 56 (85)-M-cyclopropyl-2-methyl-4-18-(4-methylmorpholin-2-yl)umethyl|amino)-6-(phenylsulfanyl)imidazo|1,2-5|pyridazin-3-yl |renzamid tm MU in v

MN MN

-- are you full? ? o nn o nn 75 mg (165 μmol) (K5)-4-(b-chloro-8--(4-methylmorpholin-2-yl)umethyl|amino)imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 5ba was converted analogously to Example 51, using benzenethiol, to obtain after processing and purification 21.6 mg (25 95) of the title compound. 1H-NMR (0M50O-ab): b- 0.49 (2H), 0.65 (2H), 1.70 (IN), 1.93 (1H), 2.13 (ZH), 2.20 ( ЗН), 2.53 (IN), 2.64 (1Н), 2.79 (1Н), 3.25-3.34 (2Н), 3.43 (1Н), 3.62 (1Н), 3 .73 (1Н), 6.10 (1Н), 7.10 (1Н), 7.42 (1), 7.45-7.51 (ЗН), 7.59-7.67 (ЗН), 7 .71 (1H), 7.92 (1H), 8.23 (1H) ppt.

Intermediate Example 5ba (85)-4-(6-Chloro-8-C(4-methylmorpholin-2-yl)methylylamino)imidazoi|1,2-B)pyridazin-3-yl)y-N-cyclopropyl-2- methyl benzamide

MU

(in Vah u in MN

MN --- Fe 25.2 M

352 MG (864 μmol) (K5)-6-chloro-3-iodo-M-((4-methylmorpholin-2-yl)methylimidazo)

P,2-B|Ipyridazine-8-amine, which was obtained according to Intermediate Example 56B, was converted analogously to Intermediate Example la, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl)benzamide, yielding after treatment and purification 372 mg (95 Fo) of the title compound.

Intermediate Example 565 (85)-6-Chloro-3-iodo-N-((4-methylmorpholin-2-yl)methylimidazo(1,2-b|Ipyridazin-8-amine tt

Vg in

Photo by MN

With -f

SI M se

And so on

AND

370 mg (1.03 mmol) of 8-bromo-b-chloro-3-iodoimidazo|1,2-5|pyridazine, which was obtained according to

Intermediate Example 1c was converted analogously to Intermediate Example 16, using 1-(285)-4-methylmorpholin-2-yl|methanamine, to obtain after treatment and purification 359 mg (85 95) of the title compound.

Example 57 4-[8-K2-Amino-2-methylpropyl]amino|-6-(4-fluorophenyl)imidazoi|1,2-BI pyridazin-3-yl)yl]-M-cyclopropyl-2-methylbenzamide

MN MN se a)

SI zm / --» zm /

IS

M M another 100 mg (242 μmol) 4-(8-(2-amino-2-methylpropyl)amino|-6-chloroimidazo|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2- methylbenzamide, which was prepared according to Intermediate Example 57a, was converted analogously to Example 1 using (4-fluorophenyl)boronic acid to give, after work-up and purification, 17.9 mg (14 95) of the title compound.1H-NMR (SOSIS): 6- 0.63 (2Н), 0.90 (2Н), 1.25 (2Н), 1.29 (6Н), 2.55 (ЗН), 2.93 (1Н), 3.27 (2Н) , 5.94 (1H), 6.34 (1H), 6.41 (1H), 7.17 (2H), 7.45 (1H), 7.81 (1H), 7.91-7.98 (ZH), 8.04 (1H) ppt.

Intermediate Example 57a 4-8-(2-Amino-2-methylpropyl)amino|-b-chloroimidazo|1,2-b|pyridazin-3-yl)-

M-cyclopropyl-2-methylbenzamide

MN.

MN. o in s -

MN zi Y --- SI M s zi

M another 1.07 g (2.93 mmol) of /M1-(b-chloro-3-iodoimidazo|1,2-b|Ipyridazin-8-yl)-2-methylpropan-1,2-diamine, which was obtained according to with Intermediate Example 570, were converted similarly

Intermediate Example 1a, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, yielding after work-up and purification 809 mg (64 Fo) of the title compound.

Intermediate Example 575

M1-(6b-chloro-3-iodoimidazo|1,2-b|Ipyridazin-8-yl)-2-methylpropane-1,2-diamine

MN.

Ve in si zi Fe! si yati

AND

2.00 g (5.58 mmol) of 8-bromo-6b-chloro-3-iodoimidazo|1,2-b|Ipyridazine, which was obtained according to

Intermediate Example 1c was converted similarly to Intermediate Example 16, using 2-methylpropane-1 2-diamine to obtain after processing and purification 1.08 g (53 95) of the title compound.

Example 58 4-I8-K(2-Amino-2-methylpropyl)amino1|-6-(1-methyl-1H-pyrazol-5-yl)imidazo

N,2-N-pyridazin-3-yl)-N-cyclopropyl-2-methylbenzamide

MN MN.

Fo la) s zm / -- --k zim /

H

MM

M M still here

100 mg (242 μmol) of 4-(8-(2-amino-2-methylpropyl)amino|-6-chloroimidazo|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 57a, was converted analogously to Example 1, using 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, to give after treatment and purification of 27.5 mg (22 Fo) of the title compound. ), 2.52 (ЗН), 2.93 (1Н), 3.23 (2Н), 4.20 (ЗН), 5.97 (1Н), 6.29 (1Н), 6.42 (1Н) , 6.64 (1H), 7.41 (1H), 7.53 (1H), 7.79 (1H), 7.86 (1H), 7.90 (IN) ppt.

Example 59 4--8-(2-Amino-2-methylpropyl)amino1|-6-(2-(hydroxymethyl)phenylimidazo

P,2-VIpyridazin-3-yl-N-cyclopropyl-2-methylbenzamide

MH MH se Dn satyny i zim 4 he is still Chek 100 mg (242 μmol) 4-(8-(2-amino-2-methylpropyl)amino|-6-chloroimidazo|(1,2-b|Ipyridazine-3 - yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 57a, was converted analogously to Example 1, using (|2-(hydroxymethyl)phenyl|roronic acid, obtaining after treatment and purification 30.0 mg (23 95) of the title compound. 1H-NMR (SOSIS): 6- 0.59 (2H), 0.85 (2H), 1.25 (2H), 1.28 (6H), 2.49 (3H) , 2.89 (1H), 3.25 (2H), 4.40 (2H), 5.30 (1H), 6.07 (1H), 6.30 (1H), 6.47 (1H), 7.38 (1H), 7.43-7.50 (ZH), 7.60 (1H), 7.64 (1H), 7.73 (1H), 7.74 (1H) mp.

Example 60

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-((4-hydroxyphenyl)sulfanylimidazo|1,2-5|Ipyridazin-3-yl)y-2-methylbenzamide ( A) and

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-((4-methoxyphenyl)sulfanylimidazo|1,2-5|Ipyridazin-3-yl)y-2-methylbenzamide ( C) he he he do same" sim" / 7" / in vm / (c) (c) - (c)

b (A) b (B) b 75 mg (181 μmol) 4-(6-chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl) "M-Cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 4-methoxybenzenethiol to give, after work-up and purification, 50 mg (43 95) of the title compound A and 8.8 mg ( 5 95) of the title compound B. 1H-NMR (0M5O-46) of A: 6b- 0.49 (2H), 0.65 (2H), 1.11 (6H), 2.21 (3H), 2.79 (1H), 3.19 (2H), 4.72 (1H), 6.12 (1H), 6.82-6.91 (ZH), 7.12 (1H), 7.42 ( 2H), 7.65 (1H), 7.70 (1H), 7.91 (1H), 8.22 (1H), 10.04 (1H) ppm 1H-NMR (SOSIS) and B: b- 0.64 (2H), 0.90 (2H), 1.39 (6H), 2.37 (ZH), 2.92 (1H), 3.24 (2H), 3.88 (ZH), 4 .09 (1H), 5.30 (1H), 5.92 (1H), 5.97 (1H), 6.36 (1H), 6.96 (2H), 7.12 (1H), 7, 50-7.58 (ZH), 7.61 (1H) ppt.

Example 61

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-|(3-hydroxyphenyl) sulfanilyimidazo|1,2-5|Ipyridazin-3-yl)y-2-methylbenzamide ( A) and

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-((3-methoxyphenyl)

sulfanilyimidazo|1,2-5|Ipyridazin-3-yl)u-2-methylbenzamide (B) it is saturated

N on N g N

M M M

(c) (in (c) and (A) and" (B) their 75 mg (181 μmol) 4-(6-chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2 -b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51, using 3-methoxybenzenethiol, obtaining after treatment and purification 26.9 mg (21 95) of the title compound A and 14.9 mg (15 95) of the title compound B. 1H-NMR (0M50-ab) of A: b- 0.49 (2H), 0.65 (2H), 1.11 (6H), 2.22 (ZH), 2.79 (1H), 3.20 (2H), 4.71 (1H), 6.21 (1H), 6.85 (1H), 6.94- 7.02 (ZH), 7.15 (1H), 7.25 (1H), 7.73 (1H), 7.74 (1H), 7.94 (1H), 8.23 (1H), 9 .73 (1H) 1H-NMR (SOSIS) oi B: b- 0.63 (2H), 0.90 (2H), 1.40 (6H), 2.37 (ZH), 2.92 ( 1H), 3.23 (2H), 3.73 (ZH), 5.94 (1H), 6.02 (1H), 6.50 (1H), 6.97 (1H), 7.13-7 .20 (HN), 7.22 (1H), 7.33 (1H), 7.56-7.63 (HN) ppt.

Example 62

M-cyclopropyl-4-76-((3-fluorophenyl)sulfanyl|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-ylI-3-hydroxybenzamide (A) and

M-cyclopropyl-4-76-((3-fluorophenyl)sulfanyl|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl/y-3-methoxybenzamide ( В) he Ге) /Ф where to sati --ь E you ZE tu (v) but (v ' 7

M M M

(c) (c) (c)

M (j) M (c) M 150 mg (349 μmol) 4-(6b-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)" M-Cyclopropyl-3-methoxybenzamide, which was prepared according to Intermediate Example 4985a, was converted analogously to Example 51 using C3-fluorobenzenethiol to give, after work-up and purification, 3.3 mg (2 95) of the title compound A and 2.5 mg (1 95) of the title compound B. 1H-NMR (0M5O-46) of A: 6b- 0.53 (2H), 0.66 (2H), 1.11 (6H), 2.80 (1H) , 3.21 (2H), 4.71 (IN), 6.24 (1H), 7.06 (2H), 7.26 (1H), 7.33-7.52 (4H), 7.86 (1H), 7.94 (1H), 8.33 (1H), 10.18 (1H) Hp 1H-NMR (0M5O-ab) and B: b- 0.55 (2H), 0.69 ( 2H), 1.11 (6H), 2.82 (1H), 3.22 (2H), 3.84 (ZH), 4.70 (1H), 6.26 (1H), 7.04 (1H ), 7.21-7.30 (2Н), 7.36 (1Н), 7.39-7.49 (ЗН), 7.84 (1Н), 7.85 (1Н), 8.44 (IN ) ppm

Example 63

M-cyclopropyl-4-16-((4-hydroxy-3-methylphenyl)sulfanyl/|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)u -2-methylbenzamide on on

Fe Fe sim" / vm /

M a M o M i o U 75 mg (181 μmol) 4-(6-chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)" M-Cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 2-methyl-4-sulfanylphenol to give, after work-up and purification, 27.6 mg (28 95) of the title compound. 1H -NMR (0М5О-46): b- 0.49 (2Н), 0.65 (2Н), 1.11 (6Н), 2.10 (ЗН), 2.20 (ЗН), 2.79 (1Н ), 3.18 (2H), 4.70 (1H), 6.11 (1H), 6.86 (1H), 6.88 (1H), 7.10 (1), 7.25 (1H) , 7.32 (1H), 7.67 (1H), 7.71 (1H), 7.92 (1H), 8.21 (1H), 9.87 (1H) ppt.

Example 64

M-cyclopropyl-4-76-((5-fluoro-2-methylphenyl)sulfanyl|-8-(2-hydroxy-2- methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y- 2-methylbenzamidon on a E is u/Fo /Fo sim" / vm /

Another 75 mg (181 μmol) of 4-(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b|pyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 5-fluoro-2-methylbenzenethiol to give after work-up and purification 47.7 mg (48 95) of the title compound. 1H-NMR (0M5O -46): b- 0.48 (2Н), 0.65 (2Н), 1.12 (6Н), 2.19 (ЗН), 2.31 (ЗН), 2.79 (1Н), 3, 23 (2H), 4.71 (1H), 6.27 (1H), 7.01 (1H), 7.06 (1H), 7.29 (1H), 7.42-7.49 (2H) , 7.57 (1H), 7.67 (1H), 7.94 (IN), 8.23 (1H) ppt.

Example 65

M-cyclopropyl-4-16-((4-fluoro-3-methylphenyl)sulfanyl|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y- 2-methylbenzamid on on sim" / vm /

M M

Buccal 75 mg (181 μmol) 4-(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide , which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 4-fluoro-3-methylbenzenethiol to give, after work-up and purification, 25.9 mg (26 95) of the title compound.1H-NMR (0M5O-46) : b- 0.48 (2Н), 0.65 (2Н), 1.11 (6Н), 2.18 (ЗН), 2.22 (ЗН), 2.79 (1Н), 3.22 (2Н ), 4.71 (1H), 6.22 (1H), 6.97 (1H), 7.08 (1H), 7.25 (1H), 7.48 (1H), 7.59 (2H) , 7.67 (1H), 7.93 (1H), 007.23 (1H) ppt.

Example 66

M-cyclopropyl-4-16-((3-fluoro-4-methylphenyl)sulfanyl|-8-(2-hydroxy-2-

methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y-2-methylbenzamidon on sim" / with vm" /

М M pure 75 mg (181 μmol) 4-(6-chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)y"N-cyclopropyl -2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51, using 3-fluoro-4-methylbenzenethiol, to give after work-up and purification 41.7 mg (42 95) of the title compound. 1H-NMR ( 0М50О-аб): b- 0.48 (2Н), 0.65 (2Н), 1.12 (6Н), 2.19 (ЗН), 2.28 (ЗН), 2.79 (1Н), 3 ,23 (2H), 4.72 (1H), 6.27 (1H), 6.99 (1H), 7.07 (1H), 7.34 (1H), 7.39 (1H), 7, 44 (1H), 7.63 (1H), 7.69 (1H), 7.94 (1H), 8.25 (1H) ppt.

Example 67

M-cyclopropyl-4-76-((3-fluoro-5-methylphenyl)sulfanyl|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y- 2-methylbenzamidon on it E and uF ue0Fo sim" / vm /

M M shchy M 75 mg (181 μmol) 4-(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b|pyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was prepared according to Intermediate Example 7a, was converted analogously to Example 51 using 3-fluoro-5-methylbenzenethiol to give, after work-up and purification, 33 mg (33 95) of the title compound. 1H-NMR (0M5O-46 ): b- 0.49 (2Н), 0.65 (2Н), 1.12 (6Н), 2.21 (ЗН), 2.30 (ЗН), 2.79 (1Н), 3.22 ( 2H), 4.70 (1H), 6.27 (1H), 7.05 (1H), 7.13 (1H), 7.16 (1H), 7.26 (1H), 7.27 (1H ), 7.70 (1H), 7.73 (1H), 207.95 (1H), 8.24 (1H) ppt.

Example 68

M-cyclopropyl-4-16-((3,5-difluorophenyl)sulfanyl)|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y-2- methylbenzamid on on to kdd sim" / E vm" /

М M pure 75 mg (181 μmol) 4-(6-chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was prepared according to Intermediate Example 7a, was converted analogously to Example 51 using 3,5-difluorobenzenethiol to give, after work-up and purification, 5.7 mg (6 95) of the title compound. 1H-NMR (0M5O-46 ): b- 0.49 (2Н), 0.65 (2Н), 1.12 (6Н), 2.22 (ЗН), 2.79 (1Н), 3.24 (2Н), 4.71 ( 1H), 6.34 (1H), 7.12 (1H), 7.16 (1H), 7.35-7.40 (ЗН), 7.71 (1H), 7.74 (1H), 7 .96 (1H), 8.25 (1H) ppt.

Example 69

M-cyclopropyl-4-16-((4-fluoro-2-methylphenyl)sulfanyl|-8-(2-hydroxy-2-

methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y-2-methylbenzamidone sieves -- similar to M, zy

М M pure 75 mg (181 μmol) 4-(6-chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 4-fluoro-3-methylbenzenethiol to give, after work-up and purification, 32.1 mg (32 95) of the title compound. 1H-NMR (0M5O -46): b- 0.48 (2Н), 0.65 (2Н), 1.12 (6Н), 2.18 (ЗН), 2.35 (ЗН), 2.79 (1Н), 3, 22 (2H), 4.72 (1H), 6.23 (1H), 6-95 (1H), 7.05 (1H), 7.15 (1H), 7.34 (1H), 7.53 (1H), 7.63 (1H), 7.65 (1H), 7.92 (1H), 8.23 (1H) ppt.

Example 70

M-cyclopropyl-4-16-(2-fluorophenyl)sulfanyl)|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamide he he sat --kk S, zi

IS

M M only 75 mg (181 μmol) 4-(6-chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl- The 2-methylbenzamide obtained according to Intermediate Example 7a was converted analogously to Example 51 using 2-fluorobenzenethiol to give, after work-up and purification, 36.8 mg (38 95) of the title compound.1H-NMR (0M5O-46): b- 0.49 (2Н), 0.65 (2Н), 1.13 (6Н), 2.18 (ЗН), 2.78 (1Н), 3.24 (2Н), 4.72 (1Н) , 6.31 (1H), 7.00 (1H), 7.03 (1H), 7.32 (1H), 7.40 (1H), 7.53 (1H), 7.61 (1H), 7.64 (1H), 7.69 (1H), 207.93 (IN), 8.22 (1H) ppt.

Example 71

M-cyclopropyl-4-/6-((4-fluorophenyl)sulfanyl|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2- methylbenzamid on on /F of sim" / 7" /

М M pure 75 mg (181 μmol) 4-(6-chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl- The 2-methylbenzamide obtained according to Intermediate Example 7a was converted analogously to Example 51 using 4-fluorobenzenethiol to give, after work-up and purification, 31.6 mg (33 95) of the title compound.1H-NMR (0M5O-46): b- 0.48 (2Н), 0.65 (2Н), 1.12 (6Н), 2.19 (ЗН), 2.79 (1Н), 3.22 (2Н), 4.72 (1Н) , 6.24 (1Н), 6.97 (1Н), 7.08 (1Н), 7.33 (2Н), 7.58 (1Н), 7.64-7.71 (ЗН), 7.92 (1H), 8.23 (1H) ppt.

Example 72

A-16-K2E)-But-2-en-2-yl|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-p)

Pyridazin-3-yl)u"-M-cyclopropyl-3-methoxybenzamidone and ne se la sim / o- --- and zm / o-.

M M

(c) M (c) M 75 mg (174 μmol) 4-(6-chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)" M-cyclopropyl-3-methoxybenzamide, which was obtained according to Intermediate Example 4985a, was converted analogously to Example 1 using (27)-but-2-ene-2-ylboronic acid, yielding after work-up and purification 26.9 mg (33 95 ) of the title compound. 1H-NMR (0M5O-46): 6- 0.57 (2H), 0.68 (2H), 1.16 (6H), 1.81 (ЗН), 1.99 (ЗН ), 2.84 (1H), 3.28 (2H), 3.89 (ZH), 4.75 (1H), 6.40 (1H), 6.48 (1H), 6.58 (1) , 7.51 (1H), 7.53 (1H), 7.85 (1H), 8.32 (1H), 8.47 (1H) ppt.

Example 73

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(2-hydroxyphenyl) sulfanilyimidazo|1,2-5|Ipyridazin-3-yl)y-2-methylbenzamide (A ) and

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(2-methoxyphenyl) sulfanilyimidazo|1,2-5|Ipyridazin-3-yl)y-2-methylbenzamide (B ) he he he si -z Fe zi z Fe zny he Ou

M M M sho (A) sho (c) sho 100 mg (242 μmol) 4-(6b-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|Ipyridazine-3- yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 2-methoxybenzenethiol, obtaining after work-up and purification 43.1 mg (35 95) of the title compound A and 5 .8 mg (4 95) of the title compound B. 1H-NMR (0M5O-46) of A: 6b- 0.49 (2H), 0.65 (2H), 1.11 (6H), 2.20 (ЗН), 2.78 (1Н), 3.19 (2Н), 4.72 (1Н), 6.14 (1Н), 6.82-6.90 (2Н), 6.97 (1Н), 7.07 (1H), 7.33 (1H), 7.44 (1H), 7.66 (1H), 7.71 (1H), 7.91 (1H), 8.22 (1H), 9 .96 (1H) Hg 1H-NMR (SOSIS) oi B: 6- 0.63 (2H), 0.89 (2H), 1.39 (6H), 2.35 (ZH), 2.91 ( 1H), 3.23 (2H), 3.77 (ZH), 4.62 (1H), 5.92 (1H), 5.97 (1H), 6.42 (1H), 6.99 (1H ), 7.03 (1H), 7.13 (1H), 7.47 (1H), 7.56-7.64 (4H) ppt.

Example 74

M-cyclopropyl-3-hydroxy-4-(6-(phenylsulfanyl)-8-(3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)benzamide and EI

In U

MN MN

Fe Ogo sim in (in o) 74

M M shchi M

29.5 mg (67 μmol) 4-/6-chloro-8-I((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl- The 3-methoxybenzamide obtained according to Intermediate Example 52a was converted analogously to Example 51 using benzenethiol to give after work-up and purification 19 mg (52 95) of the title compound. 2H), 0.88 (2H), 2.44 (2H), 2.92 (1H), 3.55 (2H), 5.81 (1H), 6.12 (1H), 6.22 (1H ), 7.22 (1H), 7.33 (1H), 7.41-7.54 (4H), 7.58-7.66 (H), 9.01 (1H) ppt.

Example 75

M-cyclopropyl-4-(6-(3-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl-g-methylbenzamidone one usso sy know the lake

M and M (c) (c) (o and b 50 mg (121 μmol) 4-(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazine-3 - yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 3-fluorophenol, obtaining after treatment and purification 13.9 mg (22 95) of the title compound. 1H -NMR (0М5О-46): 6- 0.47 (2Н), 0.63 (2Н), 1.16 (6Н), 2.14 (ЗН), 2.76 (1Н), 3.27 (2Н ), 4.74 (1H), 6.18 (1H), 7.02 (1H), 7.08-7.14 (2H), 7.16 (1H), 7.24 (1H), 7, 47 (1H), 7.67 (1H), 7.77 (1H), 7.92 (IN), 8.21 (1H) ppt.

Example 76

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-phenoxyimidazo

N,2-Shipyridazin-3-yl)y-2-methylbenzamide

Ge) Ge) du. Who do you know about zm

M o M

Chek Chek 50 mg (121 μmol) 4-(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|midazol(1,2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide , which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using phenol to give after work-up and purification 15.1 mg (25 95) of the title compound. ), 0.86 (2H), 1.38 (6H), 2.26 (ZH), 2.86 (1H), 3.29 (2H), 3.74 (1H), 5.91 (1H) , 6.02 (1H), 6.42 (1H), 7.19 (2H), 7.23 (2H), 7.41 (2H), 7.57 (1H), 7.66 (1H), 7.70 (1H) ppt.

Example 77

M-cyclopropyl-2-methyl-4-yl-16-phenoxy-8-(3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazine-3-ilubenzamide

E E

E E

In U

MN MN se se se What about A ? mg (114 μmol) 4-(6b-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl- 2-methylbenzamide, which was obtained according to Intermediate Example 10a,

was converted similarly to Example 51, using phenol, to obtain after treatment and purification 5.7 mg (9 95) of the title compound. 1H-NMR (SOSIS): 6- 0.60 (2H), 0.87 (2H), 2.29 (ZH), 2.57 (2H), 2.88 (1H), 1.97 (2H) , 5.84 (1H), 5.90 (1H), 5.97 (1H), 7.20-7.30 (4H), 7.44 (2H), 7.60 (1H), 7.73 (1H), 7.74 (1H) ppt.

Example 78 4-8-(2-Amino-2-methylpropyl)amino1|-6-((3-fluorophenyl)sulfanilyimidazo

P,2-VIpyridazin-3-yl-N-cyclopropyl-2-methylbenzamide

MN MN. и E и со оди situ ---- зх ту

250 mg (605 μmol) 4-(8-(2-amino-2-methylpropyl)amino|-6-chloroimidazo|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2- methylbenzamide, which was obtained according to Intermediate Example 57a, was converted analogously to Example 51 using C3-fluorobenzenethiol to give, after work-up and purification, 9.8 mg (C 95) of the title compound. 63 (2H), 0.89 (2H), 1.24 (6H), 1.80 (2H), 2.39 (ZH), 2.91 (1H), 3.14 (2H), 5.91 (1H), 5.97 (1H), 6.34 (1H), 7.12 (1H), 7.22 (1H), 7.32-7.42 (ЗН), 7.62 (1H), 7.64 (1H), 7.69 (1H) ppt.

Example 79

M-cyclopropyl-4-76-((3-fluoro-5-methylphenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u .2-methylbenzamide

Yi I

In U

50 mg (114 μmol) 4-(6b-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-b| pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 10a, was converted analogously to Example 51, using 3-fluoro-5-methylbenzenethiol, obtaining after treatment and purification 6.9 mg (11 95 ) of the title compound. 1H-NMR (SOCI3-CO3O0): b- 0.61 (2H), 0.88 (2H), 2.35 (ЗН), 2.39 (ЗН), 2.48 (2Н ), 2.89 (1H), 3.54 (2H), 5.89 (1H), 6.07 (1H), 6.46 (1H), 6.96 (1H), 7.17 (1H) , 7.21 (1H), 7.23 (1H), 7.63 (1H), 7.66 (1H), 7.68 (1H) ppt.

Example 80

M-cyclopropyl-4-76-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazin-3-yl)y-2-methylbenzamide and i

In R

MN MN

DU - DK siti obi i dv

M M o nn o nn mg (114 μmol) 4-(6b-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl -2-methylbenzamide, which was obtained according to Intermediate Example 10a,

was converted similarly to Example 51, using 3-fluorophenol, obtaining after treatment and purification 9.1 mg (15 95) of the title compound. 1H-NMR (SOSIS): 6- 0.60 (2H), 0.87 (2H), 2.32 (ZH), 2.57 (2H), 2.89 (1H), 3.67 (2H) , 5.87 (1H), 5.89 (1H), 6.12 (1H), 6.94-7.08 (ZH), 7.25 (1H), 7.39 (1H), 7.60 (1H), 7.72 (2H) ppt.

Example 81

M-cyclopropyl-4-76-(2-fluoro-5-methylphenoxy)-8-|((2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y). 2-methylbenzamide on on

Fe Fo sim" / oz /

E o i o i 50 mg (121 μmol) 4-(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was prepared according to Intermediate Example 7a, was converted analogously to Example 51 using 2-fluoro-5-methylphenol to give, after work-up and purification, 5.2 mg (8 95) of the title compound. 1H-NMR (0M50O -ab): b- 0.46 (2Н), 0.63 (2Н), 1.17 (6Н), 2.09 (ЗН), 2.29 (ЗН), 2.76 (1Н), 3, 29 (2H), 4.75 (1H), 6.23 (1H), 7.02 (1H), 7.10-7.16 (2H), 7.23 (1H), 7.27 (1H) , 7.62 (1H), 7.70 (1H), 7.92 (IN), 8.21 (1H) ppt.

Example 82 4-16-(3-Cyanophenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-B pyridazin-3-yl)y-M-cyclopropyl-2-methylbenzamidone He) all of you know about the change

N and N

M M another 50 mg (121 μmol) 4-(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 3-hydroxybenzonitrile to give, after work-up and purification, 5.8 mg (9 95) of the title compound. 1H-NMR (SOCIZ-COZ3O0): b - 0.63 (2Н), 0.86 (2Н), 1.42 (6Н), 2.35 (ЗН), 2.90 (1Н), 3.32 (2Н), 5.88 (1Н), 6.26 (1H), 6.66 (1H), 7.30 (1H), 7.46 (1H), 7.49-7.60 (4H), 7.65 (1H), 7.72 ( 1H) ppt.

Example 83

M-cyclopropyl-4-[6-((3-fluorophenyl)sulfonyl|-8-((3,3,3-trifluoropropyl)amino)imidazo|1,2-b|pyridazin-3-yl/y.2- methylbenzamide (A) and (85)-M-cyclopropyl-4-[6-((3-fluorophenyl)zinipu!|-8-K(3,3,3-trifluoropropyl)amino|imidazo|1,2-b| pyridazin-3-yl)y-2-methylbenzamide (B)

E E E

E E E

In U U

МН МН МН so o so (in) vm" / Oly / I Ovy zy / d U d ; r ri r r

M M M o nn o nn o nn (A) (B)

To a solution of 50 MG (121 μmol) M-cyclopropyl-4-16-|((3-fluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-5|Ipyridazine-3 -yl)-2-methylbenzamide, which was obtained according to Intermediate Example 209, in 1.0 ml of dichloromethane, 0.71 mg of methyl(trioxo)rhenium, 1.77 mg of isonicotinonitrile and 58 μl of an aqueous solution of hydrogen peroxide (30 95) were added. The mixture was stirred for 2 days at 23 "С, poured into a solution of sodium thiosulfate and extracted with dichloromethane. The organic phase was dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to obtain 14.9 mg (53,905) of the title compound A and 4.5 mg (8 9o) of the title compound B. 1H-NMR (SOSISASOSOZOB) and A: 0-0.65 (2H), 0.90 (2H), 2.47 (ZH), 2.59 ( 2H), 2.92 (1H), 3.75 (2H), 6.08 (1H), 6.76 (1H), 6.77 (1H), 7.33 (1H), 7.38 (1H ), 7.53-7.65 (ZH), 7.81 (1H), 7.82 (1H), 7.88 (1H) mp 1H-NMR (SOSIS) oi B: b- 0.65 ( 2H), 0.92 (2H), 2.55 (5H), 2.94 (1H), 3.73 (2H), 5.98 (1H), 6.37 (1H), 6.60 (1H ), 7.17 (1H), 7.46 (1H), 7.50 (1H), 7.56 (1H), 7.60 (1H), 7.74-7.84 (ЗН) ppt.

Example 84

M-cyclopropyl-2-methyl-4-(6-(phenylsulfanyl)-8-((3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-ylbenzenecarbothioamide

E sa r

IS

MN

МН х МИ и сит ---2 хх MM 87 7М и о Я р у и 59.1 mg (130 μmol) 4-(6b-chloro-8-(3,3,3-trifluoropropyl)amino|imidazo|1 ,2-5|pyridazin-3-yl)u"N-cyclopropyl-2-methylbenzenecarbotinamide, which was obtained according to the Intermediate

Example 84a was converted similarly to Example 51, using benzenethiol, to obtain after treatment and purification 7.1 mg (9 95) of the title compound. 1H-NMR (SOSIS): 6- 0.75 (2H), 1.05 (2H), 2.30 (ZH), 2.47 (2H), 3.41 (1H), 3.56 (2H) , 5.87 (2Н), 7.16 (1Н), 7.27 (1Н), 7.41-7.50 (ЗН), 7.57-7.71 (5Н) ppt.

Intermediate Example 84a 4-(6-Chloro-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-b|pyridazin-3-yl)y-

M-cyclopropyl-2-methylbenzenecarbothioamide

What about you?

IS

MN

MN

UF Fo x MI and sit ---2 zh MM

SI M ob- I u

M vn

A mixture containing 100 mg (228 μmol) 4-(6-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)y"-M- cyclopropyl-2-methylbenzamide, which was obtained according to

Intermediate Example 1ba, 25.4 mg of phosphorus pentasulfide and 0.47 ml of pyridine were heated at 115 7C for 4 hours. Water and brine were added, and the mixture was extracted several times with ethyl acetate. The combined organic layers were dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to give 65.7 mg (63,905) of the title compound.

Example 85 4-16-(3-Chlorophenoxy)-8-(2-hydroxy-2-methylpropyl)aminoimidazoli|1,2-B)pyridazin-3-yl)y"-M-cyclopropyl-2-methylbenzamidone sim " / with om /

N. Y. N

M M what more 50 mg (121 μmol) 4-(6-Chloro-8-|((2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b|pyridazin-3-yl)UM- cyclopropyl -2-methylbenzamide, which was prepared according to Intermediate Example 7a, was converted analogously to Example 51 using 3-chlorophenol to give after work-up and purification 9.3 mg (14 95) of the title compound.1H-NMR (0M5O-46) : 6- 0.47 (2Н), 0.63 (2Н), 1.16 (6Н), 2.14 (ЗН), 2.77 (1Н), 3.29 (2Н), 4.74 (1Н ), 6.18 (1H), 7.03 (1H), 7.17 (1H), 7.25 (1H), 7.33 (1H), 7.44 (1H), 7.47 (1H) , 7.67 (1H), 7.74 (1H), 7.93 (1H), 8.22 (1H) ppt.

Example 86

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(4-methoxyphenoxy)imidazo|1,2-b|pyridazin-3-yl)y.2-methylbenzamidone one sim" / with ohm /

M in M (c) M - (c) M 50 mg (121 μmol) 4-16-Chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazine-3- yl)UM-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted similarly to Example 51 using 4-methoxyphenol, obtaining after treatment and purification 22.5 mg (35 95) of the title compound. 1H-NMR (0M50-a6): 6- 0.47 (2H), 0.63 (2H), 1.16 (6H), 2.11 (ZH), 2.77 (1H), 3.27 ( 2H), 3.75 (ZH), 4.75 (1H), 6.13 (1H), 6.91 (1H), 6.98 (2H), 7.15(1H), 7.18 (2H ), 7.65 (1H), 7.77 (1H), 7.91 (1H), 8.21 (1H) ppt.

Example 87

M-cyclopropyl-4-(6-(3-fluoro-5-methylphenoxy)-8-|(2-hydroxy-2-methylpropyl)amino|imidazo

P,2-Shipyridazin-3-yl)u-2-methylbenzamidone one sim" / om / g 9. another 50 mg (121 μmol) 4-(6-Chloro-8-|((2-hydroxy-2 -methylpropyl)amino|imidazo|/1,2-b|pyridazin-3-yl)UM-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted similarly to Example 51, using 3-fluoro-5-methylphenol, with obtaining after processing and purification 12.0 mg (19 95) of the title compound. , 2.15 (ZN), 2.31 (ZN), 2.77 (1H), 3.27 (2H), 4.73 (1H), 6.16 (1H), 6.90-7.06 (4H), 7.17 (1H), 7.69 (1H), 7.78 (1H), 7.92 (1H), 8.22 (1H) ppt.

Example 88

M-cyclopropyl-4-[6-(3-fluoro-5-methylphenoxy)-8-I((3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazin-3-yl)y-2-methylbenzamide and pi

In U

MN MN situ obi dO.

Shh Shh 50 mg (114 μmol) 4-(6b-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 10a, was converted analogously to Example 51 using 3-fluoro-5-methylphenol to give, after work-up and purification, 7.6 mg (12 95) of the title compound. 1H-NMR (0M5O- 46): 6- 0.47 (2H), 0.63 (2H), 2.15 (ЗН), 2.32 (ЗН), 2.67 (2Н), 2.77 (1Н), 3.59 (2H), 6.11 (1H), 6.95 (2H), 7.03 (1H), 7.17 (1H), 7.65-7.75 (2H), 7.78 (1H), 7.93 (1H), 8.22 (1H) ppt.

Example 89

M-cyclopropyl-4-76-((3-fluorophenyl)sulfanyl|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamide he he

Fe Fe sim" / vm" / o 9- sich 300 mg (725 μmol) 4-(6-Chloro-8-|((2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b| pyridazin-3-yl)UM-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51, using 3-fluorobenzenethiol, to obtain after treatment and purification 27.9 mg (7 95) of the title compound . (2H), 4.71 (1), 6.29 (1H), 7.04 (1H), 7.12 (1H), 7.33 (1H), 7.43 (1H), 7.46- 7.53 (2H), 7.66 (1H), 7.71 (1H), 7.94 (IN), 8.23 (1H) ppt.

Example 90 4-(6--4-Chlorophenoxy)-8-(2-hydroxy-2-methylpropyl)aminoimidazoi|1,2-B)pyridazin-3-yl)y"-M-cyclopropyl-2-methylbenzamidone

Fe /Fe sy and --zhk ob

M Z M o U | o M 50 mg (121 μmol) of 4-16-Chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)UM-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 4-chlorophenol to give after treatment and purification 14.5 mg (23 95) of the title compound. 1H-NMR (0M5O-46): 6- 0.47 (2H), 0.64 (2H), 1.16 (6H), 2.13 (ZH), 2.77 (1H), 3.28 ( 2H), 4.74 (1H), 6.18 (1H), 7.00 (1H), 7.17 (1H), 7.30 (2H), 7.50 (2H), 7.64 (1H ), 7.73 (1H), 7.92 (1H), 8.22 (1H) ppt.

Example 91 4-(6-(3-Chloro-4-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo

P,2-Schipyridazin-3-yl)u-N-cyclopropyl-2-methylbenzamidon on sim" / o7tm /

N skh, N

M. E. M

(c) M (c) M 50 mg (121 μmol) 4-16-Chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)UM-cyclopropyl -2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 3-chloro-4-fluorophenol, obtaining after treatment and purification 16.2 mg (24 95) of the title compound. 1H-NMR (0M5O-46): 6- 0.47 (2H), 0.64 (2H), 1.16 (6H), 2.13 (ZH), 2.77 (1H), 3.28 ( 2H), 4.74 (1H), 6.18 (1H), 7.02 (1H), 7.18 (1H), 7.32 (1H), 7.51 (1H), 7.66 (2H ), 7.72 (1H), 7.93 (1H), 8.22 (1H) ppt.

Example 92

M-cyclopropyl-4-16-(-2,3-difluorophenoxy)-8-((2-hydroxy-2-methylpropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide he he sim" / om /

Fe

M and M also Chek 50 mg (121 μmol) 4-(6-Chloro-8-|((2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b|pyridazin-3-yl)UM- of cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 2,3-difluorophenol to give, after work-up and purification, 5.8 mg (9 95) of the title compound. 1H-NMR (SOCIZ -СО3О0): 6- 0.59 (2Н), 0.85 (2Н), 1.38 (6Н), 2.24 (ЗН), 2.86 (1Н), 3.31 (2Н), 5, 98 (1Н), 6.16 (1Н), 6.53 (1Н), 7.02-7.14 (ЗН), 7.17 (1Н), 7.47 (1Н), 7.61 (2Н) , ppt

Example 93

M-cyclopropyl-4-76-(2-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamidon on s st si zi oz Y oi

M M

Cheeks 50 mg (121 μmol) 4-16-Chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)UM-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 2-fluorophenol, obtaining after treatment and purification 4.2 mg (7 95) of the title compound. 1H-NMR (0M5O-46): b- 0.46 (2H), 0.63 (2H), 1.17 (6H), 2.08 (ZH), 2.46 (2H), 2.76 ( 1H), 4.75 (1H), 6.25 (1H), 7.03 (1H), 7.11 (1H), 7.24-7.45 (4H), 7.59 (1H), 7 .67 (1H), 7.92 (1H), 8.21 (1H) ppt.

Example 94

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(3-isopropylphenoxy)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamidone one so c sim" / obu (c) ich (c) M 50 mg (121 μmol) 4-16-Chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazine- 3-yl)UM-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51, using C3-isopropylphenol, to obtain after treatment and purification 9.0 mg (14 95) of the title compound. 1H - NMR (SOS3-СО3О0): 6- 0.58 (2Н), 0.84 (2Н), 1.22 (6Н), 1.36 (6Н), 2.24 (ЗН), 2.33 (1Н ), 2.85 (1H), 2.89 (1H), 3.27 (2H), 5.88 (1H), 6.15 (1H), 6.44 (1H), 7.02 (1H) , 7.03 (1H), 7.10 (1H), 7.17 (1), 7.91 (1H), 7.59 (1H), 7.64 (1H), 7.68 (1H) ppt .

Example 95 4-16-(4-Chloro-3-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo

P,2-VIpyridazin-3-yl-N-cyclopropyl-2-methylbenzamidone sys" / total 50 mg (121 μmol) 4-16-Chloro-8-(2-hydroxy-2-methylpropyl)amino| imidazo|(1,2-b|pyridazin-3-yl)UM-cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate Example 7a, was converted analogously to Example 51, using 4-chloro-3-fluorophenol, to give after working up and purification of 4.0 mg (6 95) of the title compound. 1H-NMR (SOS3-COrzO0): b- 0.60 (2H), 086 (2H), 1.37 (6H), 2.31 (3H) , 2.34 (1H), 2.87 (1H), 3.29 (2H), 5.89 (1H), 6.09 (1H), 6.57 (1H), 6.98 (1H), 7.09 (1H), 7.15 (1H), 7.42 (1H), 7.55 (1H), 7.67 (2H) ppt.

Example 96

M-cyclopropyl-4-[6-(3,5-dimethylphenoxy)-8-|(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2- methylbenzamide on on

Fe / Fo

Ve zmi o zi Y

M M

(c) M (c) M 50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)u /M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 3,5-dimethylphenol to give after work-up and purification 14.6 mg (27 95) of the title compound. NMR (SOSIS): 6- 0.61 (2Н), 0.87 (2Н), 1.45 (6Н), 2.28 (ЗН), 2.33 (6Н), 2.89 (1Н), 3 .31 (2H), 3.683 (1H), 5.86 (1H), 5.92 (1H), 6.59 (1H), 6.83 (2H), 6.87 (1H), 7.21 ( 1H), 7.63 (1H), 7.65 (1H), 7.73

Z0 (IN) ppt.

Intermediate Example 9ba

4-16-bromo-8-K(2-hydroxy-2-methylpropyl)aminoY|imidazo(1,2-5|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamidone on t ve MH

MN /Fe

UF -- - ---» from i) day M Ve M

FU. -f in M

III 809 MG (1.97 mmol) 1-Kb-bromo-

3-iodoimidazo|1,2-b|pyridazin-8-yl)amino|-2-methylpropan-2-ol, which was obtained according to

Intermediate Example 960, was converted analogously to Intermediate Example Ta, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, to give after treatment and purification of 659 mg (73 Fo) of the title compound.

Intermediate Example 96p 1-(6-bromo-3-iodoimidazo|1,2-B|Ipyridazin-8-yl)lamino|-2-methylpropan-2-olone

Ve ve

Ve with / Fe ! In the amount of 1.0 g (2.48 mmol) of 6,8-dibromo-3-iodoimidazo(1,2-b|Ipyridazine, which was obtained according to

Intermediate Example 9bs was converted similarly to Intermediate Example 16, using 1-amino-2-methylpropan-2-ol, to obtain after treatment and purification 915 mg (90 Fo) of the title compound.

Intermediate Example 96bs 6,8-dibromo-3-iodoimidazo|1,2-b|Ipyridazine

Wee Wee from WE

Ve zn V

A mixture containing 3.64 g (10.5 mmol) of 6,8-dibromoimidazo|1,2-b|Ipyridazine, which was prepared according to Intermediate Example 964, 2.8 g of M-iodosuccinimide, 72.6 ml of M, M-dimethylformamide was heated at 60 "C for 3 hours. 1.4 g of M-iodosuccinimide was added and heating was continued for another 4 hours. Most of the solvent was removed, water was added and the mixture was extracted with dichloromethane. The organic phase was washed with water, sodium thiosulfate solution and dried over sodium sulfate After filtration and removal of the solvent, the residue was purified by chromatography to give 3.64 g (86 95) of the title compound.

Intermediate Example 96a 6b,b-dibromoimidazo|1,2-b|pyridazine

Vi Ve du) o

SI cheni What's more,

A mixture of 5.0 (14.0 mmol) 8-bromo-6b-chloro-3-iodoimidazo|(1,2-bB|Ipyridazine, which was obtained according to Intermediate Example 1c, 30 ml of a solution of hydrogen bromide in acetic acid (33 95 ) was stirred at 120 "C for one hour under microwave irradiation. The mixture was poured into water and extracted with dichloromethane. The organic phase was washed with sodium thiosulfate and sodium bicarbonate solution and dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to obtain 3.0 g (78 95) of the title compound.

Example 97

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(3-methylphenoxy)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamidone one

Fe /Fo vm / oi /

M M

Chek Chek 50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)UM-cyclopropyl-2-methylbenzamide , which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51, using 3-methylphenol, obtaining after treatment and purification 17.1 mg (32 95) of the title compound. 1H-NMR (SOSIS): 6- 0.61 (2H), 0.87 (2H), 1.46 (6H), 2.26 (ZH), 2.37 (ZH), 2.89 (1H) , 3.31 (2Н), 5.687 (1Н), 5.94 (1Н), 6.61 (1Н), 6.98-7.09 (ЗН), 7.19 (1Н), 7.29 (1Н ), 7.59 (1H), 7.63 (1H), 7.70 (1H) ppt.

Example 98 4-i6-Chloro-8-(2-sulfamoylethyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)y-

M-cyclopropylbenzamide mon, -Z shchy

MN

Ve Fo sa sit" / shh i sm !

M

(c) M 8-bromo-6-chloro-3-iodoimidazo|(1,2-B|Ipyridazine (0.3 mmol), which was obtained according to

Intermediate Example 1c, 2-aminoethanesulfonamide hydrochloride (1:1) (0.3 mmol, 1.0 equiv.)) and

PIREA (3 equiv., 157 μl) was combined with 3 ml of MMP in a sealed flask and heated at 160 "C under microwave irradiation for 30 min. After cooling, added

14-(cyclopropylcarbamoyl)phenyl|boronic acid (1.2 eq., 74 mg), Pa(arrosy) (0.2 eq., 49 mg) and potassium carbonate (3 eq., 900 µl, 1M in water) and the mixture was heated at 80 °C overnight. After cooling, the solution was filtered and subjected to preparative HPLC to give 4-6-chloro-8-(2-sulfamoylethyl)aminoimidazo|1,2-b|Ipyridazin-3-yl)u"- M-cyclopropylbenzamide (45 mg, 35 U): ORI C-M5: CT - - 0.92 min.; t/2 (Eb kyu) 435.9 |MNUY; MUU-434.9 is required.

Intermediate Example 99 4- and 6-Chloro-8-(2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)"N-cyclopropyl-2-methylbenzamide is

Vg Fo y si Zm" / s ti cm ! nmo

M

6 g (16.7 mmol) of 8-bromo-6b-chloro-3-iodoimidazo|1,2-bB|Ipyridazine, which was obtained according to

Intermediate Example 1c, converted similarly to Example 98, using

2-methylpropan-1-amine and M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, with the result after treatment and purification of 1 .27 g (19 Fo) of the compound specified in the title.

ORI О-М5: CT-1.32 min.; t/2 (Eb'zh) 398.9 |MNYAI; MUU-397.9 is required. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.65 (2H), 0.90 (6H), 1.96 (1H), 2.35 (ZH), 2.80 ( 1H), 3.12 (2H), 6.29 (1H), 7.36 (1H), 7.84 (1H), 7.91 (1H), 7.96 (1H), 7.99 (1H ), 8.29 (1H) ppt.

Example 100

M-cyclopropyl-4-18-((2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl) benzamide

100 mg (260 μmol) 4-(6-chloro-8-K(2-methylpropyl)amino|imidazo|(1,2-b| Ipyridazin-3-yl)'M-cyclopropylbenzamide, which was obtained according to Intermediate Example 100a, was dissolved in 50 ml of ethanol and subjected to a flow of hydrogen using H-Cure with a cartridge Ra/cS 10 95

SATSACT 30 at 30 "C, 10 bar and a flow rate of 0.8 ml/min. Purification by HPLC gave 21.1 mg (23 Fo) of the title compound.

ORI C0-M5: KT-1.13 min.; t/2 (Eb,k) 350.4 |MNYAI; MUU-349.4 is required. 1H-NMR (0M5O-46): 6- 0.56 (2H), 0.67 (2H), 0.90 (6H), 1.96 (1H), 2.82 (1H), 3.11 ( 2H), 6.15 (1H), 7.54 (1H), 7.687 (2H), 8.04 (1H), 8.12 (1H), -8.21 (2H), 8.43 (1H) ppt

Intermediate Example 100ba 4-N-6-chloro-8-(2-methylpropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)N-M-cyclopropylbenzamide is 7, Fo

MN family and

Fe si zi

1 mmol of b-chloro-3-iodo-N-(2-methylpropyl)imidazo|(1,2-b|Ipyridazin-8-amine (10 ml, 0.1 M in MMP), which was obtained according to Kk! Intermediate Example 1006, 1.5 mmol

14-(cyclopropylcarbamoyl)phenyl boronic acid, 0.2 mmol Ra(arrosi) and 3 mmol potassium carbonate (3 ml, 1 M in water, 3 equiv.) were combined in a sealed flask and heated at 150 °C for 180 min After cooling, the mixture was washed with water and extracted with ethyl acetate. compounds

ORI О-М5: KT-1.29 min.; t/2 (Ebh) 384.9 |Mnya; MUM 383.9 is required. 1H-NMR (0M50O-a6): 6- 0.60 (2H), 0.72 (2H), 0.93 (6H), 2.0 (1H), 2.87 (1H), 3.34 ( 2H), 6.33 (1H), 7.92 (1H), 8.07 (2H), 8.16 (2H), 8.48 (1H) ppt.

Intermediate Example 1006 b-chloro-3-iodo-N-(2-methylpropyl)imidazo|1,2-b|Ipyridazin-8-amine

Vg and

Fon v» si no si che

122 mg of 2- methylpropan-1-amine, and the mixture was stirred at room temperature overnight.

Water was added and the mixture was extracted with dichloromethane and methanol. The organic phase was washed with water and dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to give 188 mg (96 95) of the title compound.

ORI O-M5: CT-1.36 min.; t/2 (Eb, f) 351.6 |MNYAI; required MUU 350.6. 1H-NMR (0M50O-a6): 6- 1.04 (6H), 2.00 (1H), 3.13 (2H), 6.00 (1H), 7.27 (1H), 7.53 ( 1H) ppt.

Example 101 3-(4-(2-Cyclopropyl-1H-imidazol-5-yl)uphenyl|-6-ethenyl-M-(3,3,3-trifluoropropyl)imidazo|1,2-b|Ipyridazine-8 -amine 6) and another nN det M

SI M no SO she m SHI

I o Her by nm Shk) in in 0.1 mmol of 4-(6b-chloro-8-(2-methylpropyl)amino|imidazo|(1,2-bB|Ipyridazin-3-yl)"M-cyclopropylbenzamide (1 ml, 0.1 M ip MMP), which was obtained according to Intermediate

Example 10ba, 0.4 mmol of 2,3-dihydro-1,4-benzodioxin-b-ylboronic acid (0.8 ml, 0.5 M in

MMP, 4 eq.), 0.02 mmol Pa(arrOosi?) (0.3 eq., 800 μL, 0.0375 M in MMP) and 0.3 mmol potassium carbonate (0.3 mL, 1 M in water, of eq.) were combined in a sealed flask and heated at 150 °C under microwave irradiation for 90 min. After cooling, the solution was filtered and subjected to preparative HPLC to yield 4.2 mg (8 95) of the title compound.

ORI 0-M5: CT-1.34 min.; t/2 (Eb'k) 484.6 |MNUY; MUU-483.6 is required.

The following examples of compounds were prepared analogously to the procedure described above, corresponding to the Idani boronic acid framework by LC-MS, such as retention time (CT in min.) or observed mass peak collected using LC-MS Method A, unless otherwise noted:

Gleiklo | Yesech mon mon sp po p p p sya POR Da Vova, i 1rikl: Y Structure and Title "Analytical data of

SHY nikuronnnnnnnnnnnnnnn thread casting notes shk | (Tuesday A?

And: many! | ! and | t |. And M 1 MM was detected. x and | fe 2 | Mcyclopropyl-4-(8-C(2-methylprogyl 4766 ! Goa 475 ! 102 | SI ru | aminoi-b-(naphthalen-y-ipumidazogy 25 mu ! E same I :UVD : ! | I ; і | oipyridazine- Z-lubenzamid

I | but? | from calculated from) 1 1 1 ! M I 75

С--- р- пи пи пи па В пения ня тт тт тт ши ше | (bodies and | MN Go. : | bot 0. | o UM discovered in.) ! what is it? M-cyclopropyp-4-(B-13-(tiedoxymethyl) : 6 103 PHILA : luphenyl-8-(2-methylpropyl)aminoimy MM and M are ! " : dazoi1,2-ripyridazine-Z-ldenzami shk What ! i sha | calculated Z. r | ABEe tires po o p p povo nn Dis urny what | IJ V. and Mecyclopropyl-46-(4-fluorophenyl)-B-|' shen is amino copper

ОТО ray 0 (e-methyliropyl)aminoimidazoi 1-vip I i vi Iridazine-z-ilibenzamide ! tsu | | calculated - ! ; | І 443. | ! : shk and ut and : tin ! ! : E en and I | | IAM found out that she had a problem; | M-diclopropid-ia-5-(3-methylphenia)» | lav

I.: Щ Ш х for the length of the melon still ' 105 | and. L o | b And? methylaropilyaminoinidazo | me: ve I bBipridazine-3-3pvenzamid ! ! ! | by | And calculated " и ше б 239.6 i | ! nnya dl plddtttlyutt chittt nt to the poet pnyakh rya pyati yuni nyanya inn: pyv ! she i Й i | VT x TV i

Eat! tka and | !

Code | p Y MU revealed he

2-Bipridazine-Z-ylibenzamid: | ; : | is calculated 4,536 of them are currently sold in ZO L PN and Zo OO in N WN P riv nn

Application RO : Name | Analytical data and

GB And pi pi pek U tipot pi po 2! yo | (tu ! "m I i ! And shi | | | MSU discovered «

E sh u; H 4-48-2-(vcetylaminobenigi-8-(2-me ur | shi 836 and 107 | c «Kn E | tylpropylaminoimidazog1,2-B)pyrida My! o | zin-Z-le M cyclopropylbenzamide! | neo | calculated from them | 4828 pen nn nn nn nn nn nn so far

I Vtkh1,32 and ; MV: ! and what ! I UMA discovered! : Te IF; and Mecyclopropyl-ia-18-Co-methyloronyl) a71v ov 0 ; amines-B-yquinoline-Z-iiimidazoi1,9-vipi we and I " : ! SHY MM ! and and in vo 1 vydazin-z-ilyuUenzamide | : «o : calculated « no ! : pn nnІІІOOonMOOl M хz le sce t | And the same, | 4-34 "Cyclopropylcarbamoyl)pheny | MU was also detected by Sg and | AIYA-(2-methylpropyl)aminoimidazo, | 597.6'

H 109 a set; Go and she still KI 00 avipyridazinoo- MMu still | iILEM, M-dimethybenzamide was calculated from the | 4956! | and zvnvnia nin pop p po nia nia nia nia nia nia! | ; 1 N in | (see vol

Yes! i 48 venit of State Medical University revealed x ! g" | Bcyclopropip-4-baa-methylpheniin gin I zhov (mo | Fe Ha: | 8B-Ce-methylpropyl)aminoyiimidazoi 1,2» m i i | Bipyridazine-z-iubenzamide and o | (calculated 5. re "396 nyshnshshninnia nin ny nn nn ! : t | te liV g M | | , | MU detected - and i is Shar | Mecyclopropid-ya-48-(2-methylpropi) Sk le | | dat m 1 i h amino|-in-(chnoline-o-ilmidase 12-51

She 0 | MSU: shi vk Y vidazin-Z-ilibenzamide and co | |calculated x

(App. Structure | Name 00 dnapticdata | vte1o3

Saints; and : and od and Y Ш 0001 MMY detection

1 Mecyclopropyl-4-48-(2-methylpropion)

Ol u ke : | and MU N sho vi ! rhydazine-Z-yl)ibenzamide : ! what ! calculated (21 of them | atvya nTchTtTTTtTtTtntTtTttnttttntnttnttttttniinininnn t | ovte lo , - 1

Same in | | | And MUU was found 2 ve, 4-8-(4-Carbamoipfenig)-b-(e-methyl | І echett pozhoshynn 4696

TK | and AH 2 | propyl)aminomidazoi1,2-Bipridazine- | we! | Mch, about | ZAL M-cyclopropylbenzamide: and zo 'calculated t; (4464 3-Carbamoipphenyl)-B-(e-methyl yt | 469.6 sa ! y o hirspil)aminoimidazoi 1x-vipyridazine- and mm az and - ZapuMcyclopropylbenzamide SHY : : ko : calculated | 458.6

PO EN i KON V i o nn vn

Co | | that 121 in | | | 0000 MUM detected hi ! : re I is M-cyclopropyl-4-18-(isoquinoline-Y-7)-B and some 14776 and 1 is Z, " A(-methylpropyl)aminomidazog and 2-5. mo tt them, ' MU and ! and Bo ! pividazine-3-nibenzamide to | (calculated 5.

Б (4766 и в нн пон нн шчи | вти дя | дк, еще и шо | шк | We discovered x

Ge t | 4 248-(2-Methylpropythaminoimidazo | Be

WE вн и и ; : No and : Y tiv i SG i i-o 1 PP VIpridazin-zo di inemtsikoi

Pet shi | OM! and | schi U | propipbenzamide) | and duto | | calculated -.

And Br, !

a V a oPriklo) Structure | Name. | Analytical data! What is the best way to drink? | dte 12

There is me | what What | MUM discovered "

А and Р Meadiktlopropyl-4-48-K2-methypropig and g ! in di E | : x : gvrkai (430.5

Vk Ya RN Ke -Yi s g aminoib-7t-methyl-1A-pyrazol-a-limi | MM! : i dazoi 1,2-B)pyridazine-Z-ilubenzamid What Sh uko | calculated! them | p429.5 and

Co | | Tue- 109 and ; : , and І I" Kk | sho | MMU was found х : and be | M-cyclopropyl-4-(B-(isoquinopin-vl)VI so ! seh m sha and by I 477.8

V. so 2 | e: methylprohyp)aminoimidazoi 1,9-5) | flies and I - - and tridazin-z-toenzamide | ! and | pe | | calculated with and. | 478.6 nin Mon propo p op nn Mon Fri Shk I Tue iv ! E KN and | ! eh! k. There are : | iMUU was discovered with be | For (Cyclopropylcarbamoylulfene | in : : ee BO : 253 Y

I M 4 I asvduevya: ek and honors and 119 | more g | pi--2 methylpropyl)aminovmidazogi, ma

It means: what 1. 2-Bipyridazin-bchlim-methylbenzamide What shh with rreto! | calculated their | Awww! : pen pon po po ns pon shi ny ke | Tuesday 125

PN Y . , Z Shi!

And m | 4-4 (Cyclopropylcarbamoylphenes | MUM was discovered from r С kudkniyayai: ! р пи | half-c?-methylpropylaminoimidazo i, | 516 ! и и M more 2-Oypyridazin-v- | MU i !! i me | ! : И , pyo pilrA(propane-2-l)benzamide | calculated х ж | lov i І і fnm- я A - - - sons chinny nn nn s u Ye datu zhzhtt tya zh kit UM UM Uyut U UM Uyut pika y it shi shE | | W 1.36 and H bevyih | : ! ii h ! | mA revealed « - и "С M-diclopropyl-a-(b-Cemethylaprogium

Fr o pi 14326 181 C on . amino 8-(thiophene-o-ilimidazogie-vit | more

You | Rydazine-Z-IuYuenzamide | shi dryu SHI | calculated - them (4318

GENY PON ON ON NO NN AV ЧК пн сы кр тфп,ячнвтжнжяэнннытжтвтнтжлтТ( (г жлженийннвнаилижлжлилдлждлдлтл?ллишшшши выми

Application I Structure Name Analytical data

B-- pi mon ni nn nn mon today kki kny mon: še | Gvte ate

IN N Y !

And I ! that | MUU was detected with and Psch and x / M-cyclopropyl-Я-(8-(2-methylhydropropyl) !

Sov chi sh Shto Lazo el M. 0 and amine)b-Siofen-Zchlimidazog and 2-bipi | M I I | / ' about . Vidazin-Z-ilibenzamide ! | the grid is calculated /x | azi6 rentny in | ; : | not 1 Tue 149 ! And "vn

And yang and | at 1MM found ho) and | Rα M-cyclopropyl(ε-methylprotyl) and | school write sing 1945 123 | ki sh u amino b (trifluoromethyliphenylimi ma ro y H . h I : : i ila I dazogi,2-bipridazin-Z-ilueenezamid o! , : : Leo | "calculated kh ne | : ih | 403.5 ! shk and shi

PNDYNYNY PNO in full and in p sodics; n : N u topic and | WITH ; , . !

What about me? in /MUM revealed - and 4404 3-Chloropheny-8-(2-methylpyrrolidone | 5 phenyl) and 4810 ! 124 | more Mn | dpiaminamidase and e-Bipyridazine-Z» | m ke sh- I im cyclopropylbenzamide shY koso | | calculated from ! | Their 460.0 is still NN KO blue

She is | Tue

X i shi o | MM found g ! ! S i o M-cyclopropyl-a(b(Z-methoxyphenium | 0. sk Ky i. kat | 456.6

Ia WHAT is (ee methylpropyl)amino|imidazoi 12 | MA khz: p. p! in I | "bitridazinez-ilyuenzamid, : : : : ko | prepared with (4 | 455.6 them nin p mon fr ! : ! : sun | tue

Ж n | | schi | I was revealed to MU. and Co.: | 4-18-13(acetylamino)phenyI-8-Tso-me Y g shk m m . Still yang, | 183.6! en - (Z | tipprelipiaminoiimidazog 2-biprida I mm nn r izin-ZAt-Mecyclopropibenzamide ! :

Her in neo! calculated 51 ! and and and KM | AB nshshshshshshsh tires you

Pryka Structure of Nazaa (Analytical data of today tr tr t natr t

I | t | (takh 1.48 more | p. MU revealed g te av -Be uran B(o-metyp ! - KI and | 4-81 Benzofura and Also and zv 65 27 | and bi and propylamichenmidase and 2-Vipyridazine ! in pi in Voschn mm i i | i ZA Mcyclopropylenzamide p : i azo ! Icalculated 5. i | y : | : 2 | | 465.5 p t Dt shu | teo i : nya ! ; : i ' g k : | I MU found 2. et and M-cyclopropyl-ia-6(3fluorophenia-

Ye sha av an | 15! 198 - and about | (O-methylpropyl)aminoimidase| 1.2-5ip | hmm! shk in V and | MM sho -y Iridazine-3-ilibenzamide! dv | "it is calculated that you and 84358 will leave

UNO EN OKKO Not and | Tues - 7134 : ! | not | | and I : : | Kk! | MU revealed x and | 2 | M-cyclopropyl-15-(2-methoxyphenium | zvv : ! sew and Y sadno : o, 128 a m de | )-84(o-methylpropyl)aminormidazogy 2 | hmm! "Vipyridazine-z-ibenzamid and ! about | It is not calculated she: shi ni i Shchi | CT with 1.56 : St | id

Zh 07 MM revealed d) g and 4-16-(biphenyl-a p) a-methylpropion! : ! Eugene | What AND BO in 180 | sh- XX | e g" aminoimidazo 1,2-5)pyridazine-3- My: i and i | . o . . more:

E | and -/ pip -cyclopropipbenzamide more! we | it is calculated that shk z nshshshannn: LI shin nn nn; but | Tuesday: 149 g. o | MM detected x ! ! te, Mecyclopropyl-a-(b-o-dichloropheni 00).

They are | p dova them and I day 1-8 Tso-methyliropil)aminodiimidazogi, | We are together 2-iniridazine-Z-ilibenzamide : : but calcd

K | | 4vaA she

Poikt | the structure of Miazva | Analytical data J. drank Fri drink drink ask Mon Sun

E i y I she W 38 she she : | Yam what | | MUU detected - 1 ! S ha | Macyclopropyl-4-(8(2-fluorophenip)-vva i ne i, | 544.5

C C o Co-methypropylaminoimidazoi 1 2-51p | mu -y | Yevridazine-Zchip) benzamide

Mk: | | calculated

M (443.5 nshk pnaaa VO PI t | o uta Mi? ! | nn | . ! ! | And what | MMU was found g : ! Sho: / M-cyclopropyl-ia-(B i (pidroximethy ! : : i Y !

BO zavva shi pn an pp nya sha ; t | tuesday | F | 343-4 "Cyclopropyl carbamoylifenes MA; discovered from with | games and | puv-(o-methylpropyl)aminoimidazoi, | 511.6: and N vai sh Y GK EE and more | 2-Bipyridazine-b- | MU

What iAUMA(propan-2-yl)banzamide was calculated in:

I TU and and A "35 | ri | arbamoyl)phenium8-(2-methylpropylthia / 505.6 !

Z N re x spi . I r. and she Her and | minoyimidazoi1,2-bipyridazine-b- | MU

HC and about 1 pubenzamid about calculated - ; In ex H; than them | | wow, e

II W x1.34 : ! women | ! 1 | I Kk and and | MUU was detected - and | that | 448-411, 5-Benzodioxop-ya-yl)-8-4(2-meth : | vi, | sno, so 705 136 io Ky V on y propyl)iaminoimidazoi 1,2-Biliridaz mu 19 Ko. and | I ! -o (y | inezyl-M-cycloprolylbenzamide cyto: | | calculated! wines of plates

And Pryka, ! Structure | Name Analytical data I nyn i nn nn po pn p p p kn v p nnia i zy | |in 19: more | | And!

Co |. | 01 MM detected x : : I g U | Mecyclopropyl-ia-(8-Ka-methylprotl) y

Y St and 0 amino) va -methyl-1 Nepyrazol-v- lym | Mu and shi shk m vi dazoi 1,9-bIpyridazine-z-ilibenzamide./ | write choose | | calculated

M | 429.5 sh | | Dt! and h | | | MU was detected - be І M-cyclopropip-4-4(8a-methylarogyl) І dv»

I | cit volya dec sdsiyayu PA What 4275 8 IS - Z | amino|-in-(pyridine Z-yl)imidazo1,2-51pi| MA; И: и, . : flies!

And | that | rhydazine-z-luenzamium | ! and | this | "calculated on the 8th of 1765

KE х M Ш ш сени ! MUU was detected - and Shk: in Mecycloproviy-4ch8-(2-hydroxyphenia mercury that | PO 14425 139. yan n su 8-2 methylpropyl)amino midase 2 mm sha shk : ! !

It is also I "Shpridazin-z-ip)benzamide and more pito | calculated -

Lk | 4415! !

WHILE on the stump PI or lower | o shi shee | yatt : ! Kk what | MU detected x ! ! re re З С Мециклепрепия4-ив-(З-hydroxyphenyl 2428 и и ее З з | ; у 140 СЯ и х Бе -methylpropyl)aminoimidazog 2 | Mu and solution 4: "pyridazine-z-ipeenzamide cyto" "calculated " in | | and she | 16 ren nd tt : C | | I:

WHAT | 1 MMUU was discovered х ия » | Mecyclopropyl-4-16-44-podroxyphenia. ! | g i |in nshN pav 141 ne sh-i s | c8-Pα-methylpropip)aminoimidazoi12 | mm and 1 "Vipyridazine-3-ilibenzamide | | va hidden 2 !

SHE and | | 4415

POV NN KN i ON NN Z A A A i u s Z V YN a So a p ed OO o o ah po pn NO KOP ne y

Attributes and Structure | Name and Analytical data

BANK Well, she's a little bit of a min vy s oo p V s V V NI VV p-- I I - - lo o k Z ! i ve | tet: no And: and; рі і І Х о EM revealed х і хо Іі Mdykaspropium -4-4(8-(o-methyprogpiyai vda v i

Kill her and | Shk. year, ! 145 more " s and amino-8-y4-(methylsulfonylphenyl imiu and io io and !!! nn PAK shi | OVT Z

Wi chi I I | MM. discovered and p her p; M-cyclopropy-4-8-(2-methylpropyl | 4285 ryty SHY Kr HB

Mm3 is Y nszh I amino)-bapyrimidine-o-ilimidazo 1-6 1. shchi, 0 shchi akoshi mm ! ; that : |iniridazine-z-ilbbenzamide ! ' ! about and | T and B and I are calculated

M | | 427.5 nyin nyny nn pi p nn рн ше | yatea

F | : trash! | Mecyclopropyl-4-(8-C2-methylpropyl) | ;

And | more pe | and b | virgins and 44 | : amine-bchinoline-B-itimi 1,2-bBivpi and 144 schu g | amino) bchoinoline B-imidazoi 1, 2-bivi | mA and Goa t and ridazine-Z-ylrbenzamide | ! : | tsko : s calculated

And and and:

K I "788

AI she | | | | CT "0.84 "in Ki;

And | Not M | that TMM was detected with

I | yari | Mecyclopropyl-y-(b-imidazoi 1,2-aipyr | I ! 18 dn | n-B-yl)-y o-methylpropyl)amino shkei s ze | ydin-bchlu; "Non-methylirognl, | Mmu in midazop and equipyridazine-Z-chpubenzamide! ! as : | | calculated - and 465.5th cherry zen nn S

And | ke yati this | SHO and | And, there is | M-piclopropyl-ia- (6-4 (methypcarba Z MUM was found with : ! more ! YOU she and I gu | moyl)aminocrenyl-8-C2-methylpropyl 598.5 It is only o; a: HIGHER what ! co ! k and what | amino | midazoy1,2-Bipyridazin-z-ipIyu | MU: low | enzymide | zazhovano (- and ! И | | | , and

Lo | | 497.6

OKOM PON SANOK OO tsy «UN panny nn p p nn i Pryky, S Structure r Name 1 Analytical data 1

TE | INnte 123 and ! "Kn i: rya | she | y | MU/ discovered ho

Co -8-(6-05-Cyanopyridine-Z-ip)-8-((e-methy | and other p | you; 4525 ! 147 | I and e a and lyropyl)aminoimidazog and 2 unridases | MU : : x ! | and 1 in h nnZili-M-cyclopropylbenzamide still more | Icalculated - 1 and and and | : and | sya515 ! | and : ! t | tela scha : - I . : . NI N ge | M-cyclopropyl-4- (6-4B-Methylyl 4 and MU was found to be 148 | | and se | "oxadiazal-g-ilivenite 8-(2-methylp | 5ОВ,6 r И | ropitaminoimidazo! 1,2-Bipyridazine- | MU ! | ny | Zyl)benzamide |calculated from shin yan nya: o: I I

IV Oct. -llV

A M | 5-344-Cyclopropylcarbamoylphenyl | The MUU was discovered by: I pe with N and I I vezi i | li-in-Co-methylpyroyl)aminomidazolium, 484.6 (149 vyv. and | rya A and | 2 Uypyridazine-in- | MUU ! r; - Н H no | vt-Mmethylthyridine-2-carboxamide | calculated "836

F | M-cyclopropyla-(6-i4-(dimethypkare | MU found - and ! she and .. ' s g amosuaminoYiphenite 8-Co-methylarogy | 51 la. more -k SCHO; not and SCHE; pyaminemidazo 1,2 Yuridazine-Zchl ) | MU sho ve | benzamide | calculated and them | | in that | Svt 107 !! sho '

Ж m | M-cyclopropyl-4(8-(2-methylpropyl) | MUM was revealed by kht and . and iv! | an | amino)-6-(2-oxo-AB, V. g. Goy dk , PAN NI: :

S i V | a-dihydro-1H-benzimidazole-b-lymide MUu: 9 cneto I azoii,2-5ipyridezin-3-i)benzamide calculated

Priktl. | Etructure and title "Analytical data of the current era of E

She | gentlemen "well | ! | MUuU was found 5) ek H Mecyclopropyl-aya-8-(2-methylpropyl:

Live below about | 4285 152 | tu ke | amino-b-phenylimidase 1.2-bipyridase M

I s and y nez4libenzamid x re | calculated! ze | : . | sho 4255 one frinyunttnnnnnnntnntnyatnyunya n « 2 5 «lyu liu ot yuyu opt on tynu no! ! :

N I i i : what tu Ob

Her :

F | M-cyclopropyl-a-y6-13-(hydroxymethysts | MUM detected - called

G15 and. there will be | piamine midazog1,2-vipyridazine-d- | MU : | Ke r eta-methybenzamide | calculated -x she | | 485.6 : ! and E! kn kn p a i i nn - | | !

And I | Meyclogrogyp (V.o chidvokoiachme TMAAA was found to be the same | i « | typpropip)amicheB-(1-methyl-n1H-pyra | 450.5 : seh ih and zol-alzimidazoi 1,2-Bipyridazine-z- | MU :

Ka | lu-g-methylpbenizamide | calculated n i ' nk )x | (450.5

And and! p in nn mon full p new p penny ! | yes! : about | Tuesday-097

N Y ko, and ;

Zh M | M-cyclopropene-4-6-4-hydroxymeth MU was found by x

Well E t Kk and she M gia ; ! . ! vv vuh | lifenia)-8-C0-hydroxy-2-methylproly | 486.6! | hm g | l)amino|imidazo(1.2-Bipyridazin-3- o MUU

E I va | iprgmethypbenzamide calculated x

Their | | 4856

OPO KK AK o nn sho | WHAT AND NOT | And Tue

НН зе and ІН as i Madyclopropyl-4-(8-((2-pdroxy-o-me | MUU) was detected from 156 | av | typpropyl)amino b-(pyridine-z-ilimide | 457.5; : she : God's sake | ; shines - M! . N

Their I and azo12-v|pyridazineZx and MMu and that I yl-e-methylbenzamide were calculated ho and ! vka write how

ОО о нн сю ут «2 lyu

Driving

And Shelter | Structure | Name Analytical data of Mon Tynynishysh and | and th | CT - 109 r | M-cyclopropyl-a-(8-(furan-3-yl) MUU was detected - yv? gr | 2-pdroxy-2-methylpropyl)aminoimide | 446.5 g E with I | zo 2-v|pyridazine-3- MM vaylre-methylbenzamide | calculated « seh | (58 seh ikt-120 in her K-cyclopropyl-4-46-(6-ethoxypyridine | MUU precipitated 5 more | more; | "Znyl)-8-Kα-hydroxy-2 -methylpropylria 1 501.6 58 becomes re I | mine liquid o vividanine MUM vi | i-2-methylovnzamide | calculated x vi | 500.6 tires p i p v zr | | dte To

F | Mecykpopropip-4-4643,5-dimethyli a | MUU was discovered x in | wild | goxazol-a-yl)-8-(e-hydroxy-2-methyl) 475,68 ron C propygaminoimidazol1,2-rypyridazine-

F | Mecyclopropyl-4-8-(-podroxy-2-me | МУ вкавлено тше, typpropylazamino) 6-11 H-lyrazol-z-y) | 445.5 153 | and 23; midasog! 2-b1pyridazine-Z- | mu wa | ipye-methybenzamide | calculated -e ny ny nn (ve chinny yn zhi

Her pnissnchtchchsnmochvchnninin 7 pnya i aa o o o up v i in i Prov | Structure and name and analytical data

E she A ST tt vet t tt

I | : Y N : she and ra I ! M-cyclopropyl-4-18-He-hydroxy-2-me MM was found -o and i em, | | ! her | rich | typpropip)aminerY-(1-methyl-1H-pyro 459.8

C and pke4limidazoi and echoypyridazino)" and MM! that ipu-2-methybenzamide was calculated - there are 4586 of them and ! in | (Tuesday: Ova Her

ME. more ; !

Her, | Mecyclolyvopil-Я-(8-ЦО-hydroxy-2-me | MMU was detected from) ; | And eh 4 | tylpropitaminoi-e-ch1H-pyrazole-Y-4p)i | 448.5 and Ya

GO midazoi 1,2-bipyridazine-Z» | MM and ! what | ! is | ily-2-methylbenzamide Miscalculated « : nya ! : y

M | 4455! Her water | : genus | tue: ova bei Mecyclopropyl-4-8-Ccy-podroxy-2-Me MU was detected - aka! : ! 1 tylpropylamino-b-(lyrimidine-b-ilum) 458.5

Iv t still | Idazoi 1,2-bipyridazine-Z" | MU ischna-methybenzamide was calculated

N N Y I | ! : | KM | | 457.5 : : and Y

PI M nene DOK nin nin vn p o

AI still | Tues at 8 o'clock

Ж Ж е | Macyclopropyl-yacha- (2-pdroxy-e-me | MUU was detected from

Oh | SHO iv | cry | talprolyliaminor6-(2-methypyridine-4716

VA I - i i | ! : she g Y 4-ilymidazog,2-Bipyridazine-Z-MU and I ho y I N ! under | ire-methyloenzamide |calculated 5. not:

M | | 4708th

PPD VOM i nn VA A A i nn DY OK A i PA i ia opPODDYil ny Dop po mn i fr t pp t fr fr fr t fr tn but tn tily

And YuPrykl. Structure: Name | Anaphytical data: ency nin nn nn nn p nin drinking 1 th N Y I ! | and pu |vt- o and Z ' Y N ; : : Their Y and her m Mecyclopropyl-ya-16-14-ftov- | MUU was detected by ; Con sha Y dya still still Her nya and and her Uzh bi Z-(hydroxymethyliphenyl 8-Ce-hydroke | 5046

WE ARE THESE . She and and And also | i-2"methylpropyl)amineimidazogy 2-01 MUU ! | in | pyridazineyl-methylpbenzamide was calcd

Н НВ ух | | 5OZ, 6 and | | and the fault of nnninshneshwnnnnnnnnn liny and | holy man! - ! | and x M-cyclopropyl-a-1643,b-didoya But MUU was found; I am tre in | ! ! in | -- - 7 | tran Y (2-nd hydroxy-2-methypropy 452.5 I 386 11 u. i I o | Zkh g i | puaminoiiimidazog 2-bipyridazine-z» | MUu i i | m ta i r. I uch Gir e-methypbenzamide It is calculated

And m: І : their | Yav sew ni and nn

The following examples of compounds were prepared in a similar manner to the procedure described in Example 51 using an argyorgiae alcohol or a thiol bBiyldipid BioscK LC-MS data such as retention time (CT in min) or observed mass peak was collected using LC-MS

Method A, unless otherwise noted):

acc. | Structure | Name! Anaphytical data

Beyatyat r nn in N. on nn in NN ! and oh! : ! in | Tue: 103. ! | Mecyclopropyl-4-(85-hydroxy-2-me) MUM was detected from: Bile: i: essens in sylpropigtuamine b-(quinoline-o-yloxy) and 523! 187 | and a: What! and with imidazoi .2-BipyridazanZ-MU; | tsuto ipi-2-methypbenzamide was calculated from

En M-cyclopropyl-(8-(Ochidroxy-2-me | MI) was found -

M, oh Ch p N : : y - i 1 vo t | typpropylaminoi-b-(quinoline-v-yloxy) 523.5 (I 0 | Zebchettaetutya r. khvy ! and ! (e- | midazoi 1,2-0|)pyridazin-o» MI

And And their and And .

It is in | ipremethipbanzamid | calculated -

A: M! and ! shi 522.6

THEY NN NO NN NN NN OO OO KO V Ek A V

Use | The structure of the connection: | Anali and i and off stutuva 00001000 0MvlychNidaN

ШЙ вх втями : ! ich: and and and that | Mediclopropyl-2-methyl-b-quinoline. | MMU revealed t : Ko Meoda : : g her z sakh 1 B-yloxy)-803,3, 8-trifluoropropia | 5476 java Ko AI ! and minozimidazogi.2-vipridazine-Z" | MUU : : x 1. ! I: Kk ra ipibenzamid, calculated - b. and led in : va tia

And | B | KT xx 120 -k svv | Mecyclopropyl-2-methyl-y-(b-(quinolium) was detected with

More shadows, Ko. . and and "70 sh Y KE "v-yloxy) 8-83, H-trifluoroprolntsa and 547.6 th OM t h b, i i x ! and o : minogmidazoi1.2-vipyridazin-Z» MU ! ak and R. and : and vo and in)benzamide | calculated in : in the most | Mr. Bav : | shi | : cha | And I ate it! | B.! i : | Well, | I

N i : «dr it, | ! then g LET | 3-trifluoropropyl)aminoimidazoi!, 2-r 518.8 r | Ipyridazinez - M and Z | : :

I | Bia | iprMcyclopropute-methyloeunzamide (calculated - i | i: z ; | i i : i | 512

Her. them | (ite nn nn v nn nn nn nn mn nn nn v ny nn pnia: sen Y t | I VT x 1,6

From: Shk | and 4-48-(cyclohexypsulfanyl-αЯ-Я 0 ММ revealed 19 | CA droxy-2-methylpropyl)aminoimidazoi | 494.7 that | I») about pa-vipyridazine-Z- | M! also ipi-Mcyclopropyl-2-methylbenzamide and calculated

Ah | | AZ3 7 nen v nn nn p pon nn stump vn sho | (tu 096 re m | MAcyclopropyl-ia-t8-Ce-hydroxy-e-me | MU found - 73 | la I, | tylpropylamino|-b- pyridine-Zaloxy | 578.6 z | - ; : y: 7 imidazog el iN-Z- Mu i

And Zimidazoi )piridaza and more ipra-methylbenzamide | calculated

M | 472.6 and pn a p p o o i PA lvykl. Stusu 000000neva 00000000 Analimchni dvni sk she | (vteia: "uv Mecyclopropild-methyg a bch (pyrides MUU detected by hyaz | и | nezchloksy)- 8-3 5 5-trifluoropropyl) 14975 what | g where | aminoimidase 2-bipyridazin-3- | MM

Y Between Ag and I: I and ipibenzamid "calculated xx what; di

M | 495.5

Example 175 3-(4-(2-Cyclopropyl-1H-imidazol-5-yl)uphenyl|-6-ethenyl-M-(3,3,3-trifluoropropyl)imidazo|1,2-b|Ipyridazine-8 -amin oh What

MN se dm vi zh - Y so! won shu mn on 52 mg (150 μmol) of b-chloro-3-iodo-N-(2-methylpropyl)imidazo|(1,2-b|Ipyridazin-8-amine, which was obtained according to Intermediate Example 10006, was converted similarly Intermediate

Example 1a, using phenylboronic acid, yielding after treatment and purification 7.4 mg (17 Fo) of the title compound.

ОРИ С-М5: CT-1.50 min.; t/2 (Eb'zh) 301.8 |MNY; necessary

MUU-300.8.

The following examples of compounds were prepared in a similar manner to the procedure described above, using arrgorgiae boronic acid bBiiiidiporioscK LC-MS data, such as retention time (QT in min) or mass peak observed, were collected using LC-MS

Method A, unless otherwise noted):

pi AI | Kt.

C | Stump! Mn | ; M I 20.1 MM was found to be ey | ach6-Chloro-b-(2-methylpropyl)aminoiy 3448 176 i) midazoi1,2-bipyridazine-Z- | I gy and Y ipdbenzamide ! o calculated x : in nn; sthoch : | ZAZ, you are Tue-129

What 00000 | It was discovered that 4-4 8-Chlor-B-Co-methylpropip)amino zva

I and pi I Mn | . and nen 177 m dya midazoi 1, 2-vipyridazin-3- Mu schi P but Mcyclopropylosenzamide

Ж was calculated - and» Z83.9

Co | W 1.22 and (B-Chlor-v liaminoi MUU was detected - : sya 4-48-Chloro-8-K2-methypropyl)iaminoi sho | | zve8

SV M midazog 1 2-Ю1pyridazin-y- Mo! Yay! bye! isch-M-methybenzamide ! calculated -x dnbcho calculated from : | Z57.8 t! CT xx 1. . | UIA was discovered from

Y a A v-chloro-B-ce-methylpropyl amino I and

R še s | Shk Z95.9 tv | | From midazoi 1,2 vIpridazineZ" mu ve: il Kn(poopan-e-ipivbenzamide ! | and calculated

No, no!

Ka 385.9 ke | вт-127 "вв шо | | We/ revealed x shk t ya, v-Chlor-i-185-chloro-v-c2-methylpyrogy 3533 s ia oda 180: "shk zaminohymidazoi 2-viridazine M ! ia Y Y

It contains M-methyloenzamide

Heh heh

2-Chloro-4-46-chloro-8-(2-methylhydroyl seba) 419.3 181 | de amino midazo 1,2-Bpividazine-Z- m

M is and | ! Hey A | and M-cyclopropibenzamide

And ben | calculated - and | m left o tu 142

Gee 00000001 Mu was discovered! She eats a4B-Chpor-e-ce-methylpropylamine ! | son | | ! 404.9 (182 Na 1.2-BIpyridazine-Zchanama

And | fluoro-M-(propan-?-yl)benzamide what is | calculated sx ! | in ' ! yah 403.9 yo tu 2140

397.9 183 i -Benzoxazal-y-yl M-(2-methylpropane) p1pyridazin-8-amine: calculated 5.

A 395.9 and Tu e095 1 z. scha v-Chlor-344-02 ilnamide | in which is chloro-z-a2-cyclopropip-1H-imi, that -fluoro-z-a-(2-cyclopropyl-TH-imid) 075 184 ze azole-itevenitme-methylpropni o and i M Mu zhmidazo 1, 2-pyridazine-in-amine was calculated -,, , and 7 y

Example 185 4-(6-Chloro-8-Cthiophen-2-ylmethyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)y-

M, M-dimethylbenzamide that 82 МН /Фо

МН 7, Y ol

AND

-m 9 and 117 mg (300 μmol) of b-chloro-3-iodo-N-(thiophen-2-ylmethyl)imidazo|1,2-b|Ipyridazin-8-amine, which was obtained according to Intermediate Example 185a, was converted similar to Intermediate

Example 100a, using |4-(dimethylcarbamoyl)phenyl|bronic acid, obtaining after treatment and purification 15 mg (12 95) of the title compound.

ОРИ О-М5: CT-1.25 min.; t/2 (Ebu) 412.9 |MNYAI; MUU 411.9 is required.

Intermediate Example 185a b-chloro-3-iodo-N-(thiophen-2-ylmethyl)imidazo|1,2-b|Ipyridazin-8-amine which

VG MN

SOYU - co

SI with Fe, ! ! b-chloro-3-iodo-M-(thiophen-2-ylmethyl)imidazo|1,2-b|Ipyridazin-8-amine was obtained similarly to

Example 1006, using 1-(thiophen-2-yl)methanamine, which was obtained according to Intermediate

Example 1c, with obtaining after treatment and purification 80 95 of the compound specified in the title.

The following example compounds were prepared in a similar manner to the procedure described in Example 185, using arrgorgic boronic acid Biidipud BioskK LC-MS data, such as retention time (QT in min) or mass peak observed, were collected using LC-MS

Method A, unless otherwise noted):

"Example | Lathe Name Analytical data about

Her VT is 1.24

S. 2-Chloro-a-(8-xpor-b-(thiophen--ylmethyl | MMU was found to be 5,186 from uaminomidazog 2-Bipyridazine-z- 4333 and that iti-M-methinebenzamide MMU was calculated to be -4323

And but and VT 1 1 MA ee, 2-Xpor-Я-b-chloro-B-Cthiophen-e-ylmethyl | MUM was discovered - in? in Zamino|imidazoi1,2-vipyridazin-3- 459.4 sei in i ip M-cyclopropylbevzamide MUM calculated dn "458.4 them

N Z Y d

Iv Tu "140

Kok ach6-Chloro-Vthiophene-2-ismethyp)amino| | MUM detected x ! i: : 188 piy c midazog 1,2-5|pyridazineZ-ip)-2-orto-

M r MApropane-e-ip)benzamide MUM calculated and ra "43

S. Vt 37 ! Mon :

And 7-х b-Chlov-Z-gZ-(cyclopropylaminomi, 2-be | MUU was found -i : - и and yive | с мк nzoxazol-b-ipi-Xtiophren-ouyumethyl 457.9 that midazoi1,2-Bipridazine- B-amine MUU was calculated. 2 ! še « 430.8

AND

Example 192

M-cyclopropyl-4-IV-((25)-2-К4НВ)-2,2-dimethyl-1,3-dioxolan-4-yl|-2-hydroxyethyl)amino)-6-(1-methyl-1 N-pyrazol-5-yl)imidazo|1,2-b|pyridazin-3-yl|bSenzamid mo Mo te te

MN MN se Dn

SI zy / Fe zm /

MM

(in (in in y

To the mixture 52 MG (94 μMOL) 4-(b-chloro-8-((25)-2-(48)-2,2-dimethyl-1,3-dioxolan-4-yl|-2-hydroxyethyl)amino )imidazo|(1,2-B|pyridazin-3-yl|-M-cyclopropylbenzamide, which was obtained according to Intermediate Example 192a, 33 mg of 1-methyl-1H-pyrazol-5-yl)boronic acid, 6.5 mg of tetrakis(triphenylphosphine)palladium in 1 ml of ethanol and 1 ml of toluene, 0.26 ml of 10 95 aqueous sodium bicarbonate solution was added, and the mixture was stirred at 120 "C for 2 hours under microwave irradiation. Then the mixture was filtered, the solvent was removed, and the residue was purified by chromatography with obtaining 36 mg of the compounds specified in the title. 1H-NMR (0M50-46): 6- 0.49-0.68 (4H), 1.24 (3H), 1.32 (3H), 2.62 (1H) , 3.31 - 3.95 (ZN), 3.60 - 4.05 (ZN), 4.12 (ZN), 6.54 (1H), 6.85 (1H), 7.91 (1H) 7.90 (2H), 8.07 (1H), 8.18 (2H), 8.45 (1H), mp.

Intermediate Example 192a 4-(b-chloro-8-((25)-2-(48)-2,2-dimethyl-1,3-dioxolan-4-yl|-2-hydroxyethyl)amino)imidazo|1, 2-b|pyridazin-3-yl|-H-cyclopropylbenzamide

Ho

Ho Mn (vi tn -608-K90-0Й5- si zny si si ! oh we

b

00 MG (684 μMOL) (15)-2-(b-chloro-3-iodoimidazo|1,2-b|Ipyridazin-8-yl)amino|-1-(48)-2,2-dimethyl-1, C-dioxolan-4-yl|ethanol, which was obtained according to Intermediate Example 1926, was converted similarly

Intermediate Example and, using I4-(cyclopropylcarbamoyl)phenyl|boronic acid, to obtain after work-up and purification 17 mg (5 95) of the title compound.

Intermediate Example 1926 (15)-2-((b-chloro-3-iodoimidazo|1,2-b|pyridazin-8-yl)amino|-1-(48)-2,2-dimethyl-1,3- dioxolan-4-yl|estanol

Ho

Ve M -- shsh MN with zn se

And what. with

AND

700 mg (1.95 mmol) of 8-bromo-6b-chloro-3-iodoimidazo|1,2-5|pyridazine, which was obtained according to

Intermediate Example 1c, converted similarly to Intermediate Example 16, using (15)-2-amino-1-(4H)-2,2-dimethyl-1,3-dioxolan-4-yl|ethanol, obtaining after treatment and purification 512 mg (60 95) of the title compound.

Example 193

M-cyclopropyl-4-18-(2-methylpropyl)amino|-6-(methylsulfanyl)imidazoi|1,2-BI pyridazin-3-yl)ibenzamid se se se s cho. With what in o in o

Solution 450 MG (1172 μmol) 4-(b-chloro-8-(isobutylamino)imidazo

P,2-5-Ipyridazin-3-yl|-N-cyclopropylbenzamide, which was obtained according to Intermediate Example 100a, and 330 mg (4690 μmol) of sodium methyl sulfide in 8 ml of dimethyl sulfoxide were heated for 60 min. at 70 "C in a microwave oven. Then the mixture was poured into water and the precipitate was collected and dried in vacuo to give 460 mg of the title compound as a white solid. 1H-NMR (0M5O-ab): 0- 0.52-0 .71 (4H), 0.88 (6H), 1.94 (1H), 2.56 (ZH), 2.84 (1H), 3.08 (2H), 6.08 (1H), 7, 49 (1H), 7.88 (2H), 7.97 (1H), 8.22 (2H), 8.43 (1H) ppt.

Example 194 (85)-M-cyclopropyl-2-methyl-4-(8-(2-methylpropyl)amino1|-6-

IKtetrahydrofuran-2-ylmethyl)sulfanilyimidazo|(1,2-b|pyridazin-3-yl)ibenzamide with MM (in! with MM sim sr M u o u o

A solution of 45 mg (377 μmol) of (K5)-tetrahydrofuran-2-ylmethanethiol in 1 ml of dimethylsulfoxide was treated with 14 mg (350 μmol) of sodium hydride and stirred at room temperature for 2 hours. Then 100 mg (251 μmol) of 4-(b-chloro-8-(isobutylamino)imidazo|1,2-b|pyridazin-3-yl|-H-cyclopropyl-2-methylbenzamide, which was obtained according to

Intermediate Example 194a was added and the mixture was heated for 2 hours at 70°C. The mixture was then purified by reverse phase chromatography to give 12 mg of the title compound. 1H-NMR (0M50-46): b- 0.48-0 .68 (4H), 0.88 (6H), 1.63-1.99 (4H), 2.36 (ZH), 2.81 (1H), 3.08 (2H), 3.22-3 ,36 (2H), 3.62 (1H), 3.76 (1H), 4.12 (1H), 6.04 (1H), 7.32 (1H), 7.50 (1H), 7, 90 (1H), 7.93 (1H), 8.04 (1H), 8.29 (1H) ppt.

Intermediate Example 194a 4-(b-Chloro-8-(isobutylamino)imidazo|1,2-b|pyridazin-3-yl|-H-cyclopropyl-2-methylbenzamide this is uFya

MN si zu s z

And about 3.54 g (10.1 mmol) of 6-Chloro-3-iodo-N-isobutylimidazo|1,2-b|Ipyridazine-8-amine, which was obtained according to Intermediate Example ZB, was converted similarly to Intermediate

Example and using (|4-(cyclopropylcarbamoyl)-3-methylphenyl|boronic acid, obtaining after treatment and purification 1.79 g (45 95) of the title compound.

Example 195

M-cyclopropyl-2-methyl-4-18-(2-methylpropyl)amino|-6-(1H-pyrazol-5-yl)imidazo|1,2-b|pyridazine-3-ylibenzamid se dn

SI zi / poh zm /

With meMN in o in o

To the mixture 125 MG (314 μmol) 4-(b-chloro-8-(isobutylamino)imidazo

P,2-5-Ipyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, which was obtained according to Example 194a, 111 mg (942 μmol) of 1H-pyrazol-5-ylboronic acid, 44 mg of tetrakis(triphenylphosphine)palladium in 2 ml of ethanol and 2 ml of toluene, 0.63 ml of 10 95 aqueous sodium bicarbonate solution was added, and the mixture was stirred at 120 "C for 2 hours under microwave irradiation. The mixture was then filtered and concentrated and purified by chromatography to give 41 mg of the title compound 1H-NMR (0M50-a6): b- 0.48-0.69 (4H), 0.91 (6H), 2.02 (1H), 2.39 (ZH), 2.82 (1H) , 3.17 (2H), 6.72 (1H), 6.78 (1H), 7.39 (1H), 7.85 (1H), 8.00 (1H), 8.10 - 8.17 (2H), 8.29 (1H), mp.

Example 196

M-cyclopropyl-2-methyl-4-18-(2-methylpropyl)amino|-6-(methylsulfanyl)imidazo|1,2-b|pyridazine-3-ylibenzamid

A solution of 50 mg (126 μmol) of 4-(1b-chloro-8-(isobutylamino)imidazo|1,2-b|pyridazin-3-yl|-1-cyclopropyl-2-methylbenzamide, which was obtained according to

Example 194a and 35 mg (503 μmol) of sodium methyl sulfide in 1 ml of dimethyl sulfoxide were heated for 30 min. at 70 "C in a microwave oven. Then the mixture was poured into water and the precipitate was collected and dried in vacuo to give 26 mg of the title compound as a yellow solid. 1H-NMR (0М50-а6): 6- 0.47-0 .68 (4H), 0.88 (6H), 1.94 (1H), 2.35 (ZH), 2.55 (ZH) 2.80 (1H), 3.08 (2H), 6.06 (1H), 7.32 (1H), 7.47 (1H), 7.90 (1H), 7.98 (1H), 8.05 (1H), 8.29 (1H), mp.

Example 197

M-cyclopropyl-2-methyl-4-18-(2-methylpropyl)amino|-6-«(phenylsulfanyl)imidazo|1,2-b|pyridazin-3-ylibenzamid ka o. si zmu vi u o u o

A solution of 180 mg (1634 μmol) of thiophenol in 10 mL of dimethylsulfoxide was treated with 64 mg (1608 μmol) of sodium hydride and stirred at room temperature for 2 hours.

Then 100 mg (251 μmol) of 4-(b-chloro-8-(isobutylamino)imidazo|(1,2-BI pyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide) was added, which was obtained according to Intermediate

Example 194a, and the mixture was heated for 1.5 hours at 140 °C. The mixture was then poured into ice water and the precipitate was collected and then purified by normal phase chromatography to give 112 mg of the title compound. 1H-NMR (0M5O-ab) : 0- 0.48-0.69 (4Н), 0.84 (6Н), 1.87 (1Н), 2.21 (ЗН), 2.79 (1Н), 3.03 (2Н), 5 .99 (1H), 7.10 (1H), 7.49 (ZH), 7.61-7.71 (5H), 7.92 (1H), 8.24 (1H), mp.

Example 198

M-cyclopropyl-2-methyl-4-18-(2-methylpropyl)amino|-6-"phenylsulfonyl)imidazo|1,2-b|Ipyridazin-3-yl)benzamide no che Yes

Fe, Fe, 57 M V M o

In | In i

To a solution of 105 mg (223 μmol) of M-cyclopropyl-2-methyl-4-(8-(2-methylpropyl)amino|-6-(phenylsulfanyl)imidazo|1,2-5|pyridazine-3-ilubenzamide, which was obtained according to

Example 197, 684 mg (1113 μmol) of OHOME (potassium peroxymonosulfate) was added to 15 ml of OME in small portions. The mixture was stirred overnight, then cooled to 0 C and poured into 200 ml of cold water. The precipitate was collected and purified by normal phase chromatography to give 97 mg of the title compound as a yellow solid. 1H-NMR (0M5O-ab): 0- 0.50-0.69 (4H), 0.91 (6H), 1.99 (1H), 2.30 (ZH), 2.56 (1H), 3.41 (2H), 4.31 (1H), 6.71 (1H), 7.28 (1H), 7.66-7.81 (5H), 8.03 (2H), 8.12 (1H), 8.91 (1H), 8.43 (1H) ppt.

Example 199 3-(4-(Cyclopropylcarbamoyl)-3-methylphenyl|-M-(2-hydroxyethyl)-8-

K2-methylpropyl)amino|imidazo|!1,2-5|Ipyridazine-b6-carboxamide

Fe N li) sy zy not zy s i

In o in o

A solution of 100 mg (251 μmol) of 4-(b-chloro-8-(isobutylamino)imidazo|1,2-BI pyridazin-3-yl|-H-cyclopropyl-2-methylbenzamide, which was obtained according to Example 194a, 46 mg (754 μmol) aminoethanol, 66 mg (251 μmol) molybdenum hexacarbonyl, 80 mg (754 μmol) sodium bicarbonate, 5. mg (25 μmol) palladium(I) acetate, and 7.3 mg (25 μmol) tri-tert-butylphosphine tetrafluoroborate in 3 ml of dioxane was heated in a microwave oven for 2 hours at 140 "C. Then the mixture was immediately transferred to reverse-phase chromatography to obtain 13 mg of the title compound. 1H-NMR (0M5O-ab): 0- 0.48-0 .69 (4H), 0.91 (6H), 1.99 (1H), 2.38 (ZH), 2.81 (1H), 3.17 (2H), 3.38 (ZH), 3, 53 (2H), 5.99 (1H), 6.61 (1H), 7.36 (1H), 7.84 (1H), 8.00-8.09 (ZH), 8.16 (1H ), 8.29 (1H), ppt.

Example 200

M-cyclopropyl-4-18-(2-methylpropyl)amino|-6-(methylsulfonyl)imidazoi|1,2-BI pyridazin-3-yl)ibenzamide what what zvy hvy -- - more) u o u o

To a solution of 410 mg (1037 μmol) of M-cyclopropyl-4-[8-((2-methylpropyl)amino|-6-(methylsulfanyl)imidazo|1,2-b|Ipyridazine-3-ylibenzamide, which was obtained according to

Example 193, in 15 ml of OME and added in small portions 1912 mg (3110 μmol) OHOME (potassium peroxymonosulfate). The mixture was stirred overnight, then cooled to 0 °C and poured into 200 mL of cold water. The precipitate was collected and dried in vacuo to give 291 mg of the title compound as a yellow solid. 1H-NMR (0M5O-ab): 0- 0.53-0.71 (4Н), 0.91 (6Н), 2.00 (1Н), 2.84 (1Н), 3.20 (2Н), 3.38 (ЗН), 6.58 ( 1Н), 7.92 (2Н), 8.19-8.23 (НН), 8.37 (1Н), 8.46 (1Н), m.p.

Example 201

M-cyclopropyl-2-methyl-4-18-(2-methylpropyl)amino|-6-(propylsulfanyl)imidazo|1,2-b|Ipyridazin-3-yl)benzamide

A solution of 100 mg (251 μmol) 4-(b-chloro-8-(isobutylamino)imidazo

P,2-5-Ipyridazin-3-yl|-N-cyclopropyl-2-methylbenzamide, which was obtained according to Example 194a, and 49 mg (503 μmol) of sodium propane-1-thiolate in 1 ml of dimethylsulfoxide were heated for 60 minutes. at 70"C in a microwave oven. Then the mixture was purified by reverse-phase chromatography to give 18.5 mg of the title compound. 1H-NMR (0M50-ab): 0- 0.49-0.66 (4H), 0.88 (6H), 1.00 (ZH), 1.74 (2H), 1.94 (1H), 2.36 (ZH), 202.79 (1H), 3.05-3.15 ( 4H), 6.02 (1H), 7.33 (1H), 7.47 (1H), 7.90 (1H), 7.96 (1H), 8.03 (1H), 8.29 (1H ) ppm

Example 202

M-cyclopropyl-2-methyl-4-18-(2-methylpropyl)amino|-6-(1-methyl-1H-pyrazol-5-yl)imidazo|1,2-b|pyridazine-3-ylbenzamide

Fo ne si zi / she zm / we, ni o ni o

b b

To the mixture 100 mg (251 μmol) 4-(b-chloro-8-(isobutylamino)imidazo

P,2-5-Ipyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, which was obtained according to Example 194a, 95 mg (750 μmol) 1-methyl-1H-pyrazol-b5-yl)boronic acid, 35 mg tetrakis(triphenylphosphine)palladium in 2 ml of ethanol and 2 ml of toluene was added to 0.5 ml of 10 95 aqueous sodium bicarbonate solution, and the mixture was stirred at 120 "С for 2 hours under microwave irradiation. Then water was added and the organic layer was washed with water and brine , concentrated and purified by chromatography to give 99 mg of the title compound. ), 2.36 (ZN), 2.80 (1H), 3.21 (ZN), 4.13 (ZN), 6.46 (1H), 6.90 (1H), 7.37 (1H) , 7.50 (1H), 7.65 (1H), 7.92 - 7.97 (H), 8.29 (1H) ppt.

Example 203

M-cyclopropyl-2-methyl-4-16-(methylsulfanyl)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)ibenzamide and EI

In U

МН МН си зи 08

In o In o

The title compound was prepared by the procedure described in Example 193 using 4-(6-chloro-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)" M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 10a. 1H-NMR (0M50-46): b- 0.48-0.70 (4H), 2.36 (3H), 2.54-2 .70 (6H), 2.682 (1H), 3.54 (2H), 6.16 (1H), 7.35 (1H), 7.51 (1H), 7.92 (1H), 7.97 (1H), 8.05 (1H), 8.28 (1H), mp.

Example 204

M-cyclopropyl-4-[6-((2-hydroxyethyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide in. in. shchi shchi chn MN sim" and I sing Ov Shcho shchi shchi

The title compound was prepared by the procedure described in Example 194 using 4-(6-chloro-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)" M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 10a. 1H-NMR (0M50-46): b- 0.47-0.70 (4H), 2.36 (3H), 2.53-2 .70 (4H), 2.81 (1H), 3.52 (2H), 3.71 (2H), 4.97 (1H), 6.13 (1H), 7.33 (1H), 7, 53 (1H), 7.92 (1H), 8.02 (1H), 8.29 (1H), mp.

Intermediate Example 205 (85)-4-(6-Chloro-8-((3,3,3-trifluoro-2-hydroxypropyl)amino|imidazo(1,2-B pyridazin-3-yl)y"-M- cyclopropyl-2-methylbenzamide

IS

And

IS

E MN and XX

MN x MM

650 MG (1.60 mmol) (k5)-3-((b-chloro-3-iodoimidazo P1,2-VIpyridazin-8-yl)amino|-1, 1,1-trifluoropropan-2-ol, which was obtained according to Intermediate Example 205a, was converted analogously to Intermediate Example 1a, using

M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, which was obtained according to Intermediate Example 7p, with a yield after treatment and purification of 430 mg (59 Fo) of the title compound. 1H-NMR (0M50-ab): b- 0.48-0.68 (4H), 2.36 (ZH), 2.81 (1H), 3.45-3.62 (2H), 4.91 (1H), 6.40 (2H), 6.58 (1H), 7.37 (1H), 7.81 (1H), 7.85 (1H), 7.90 (1H), 8.00 ( 1H), 8.29 (1H), mp.

Intermediate Example 205a (85)-3-(b-chloro-3-iodoimidazo|1,2-b|pyridazin-b8-yl)amino|-1,1,1-trifluoropropan-2-ol

IS

E ve y rem MN

To -- sim - F ! x si i

AND

8-bromo-6-chloro-3-iodoimidazo|(1,2-B|Ipyridazine, which was obtained according to Intermediate

Example 1c was converted analogously to Intermediate Example 16, using (85)-(3,3,3-trifluoro-2-hydroxypropyl)amine to obtain the title compound.

Example 206 (85) M-cyclopropyl-2-methyl-4-(6-(methylsulfanyl)-8-((3,3,3-trifluoro-2-hydroxypropyl)amino|imidazo|1,2-5|Ipyridazine- 3-ilubenzamide

E E

E E

Ro bor

MN MN si zy zvy u o U o

The title compound was prepared according to the procedure described in Example 193 using (K5)-4-(6-chloro-8-((3,3,3-trifluoro-2-hydroxypropyl)amino|imidazo|1,2-BI) pyridazin-3-yl)y"-M-cyclopropyl-2-methylbenzamide, which was obtained according to Example 205. 1H-NMR (OM5O-ab): 6- 0.48-0.70 (4H), 2.36 ( ЗН), 2.56 (ЗН), 2.80 (1Н), 3.47 (1Н), 3.58 (1Н), 4.30 (1Н), 6.19 (1Н), 6.56 (1Н ), 7.29 (1H), 7.35 (1H), 7.93 (1H), 7.97 (1H), 8.06 (1H), 8.28 (1H), mp.

Example 207

M-cyclopropyl-2-methyl-4-[6-(phenylsulfanyl)-8-((3,3,3-trifluoropropyl)amino]imidazo|1,2-b|Ipyridazin-3-yl)benzamide

In U

МН МН ke -- oh sis zi s zh you tsi shcha

The title compound was prepared by the procedure described in Example 197 using 4-(6-chloro-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)" M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 10a. 1H-NMR (OM50-46): b- 0.48-0.70 (4H), 2.20 (3H), 2.54-2 .70 (4H), 2.682 (1H), 3.50 (2H), 6.13 (1H), 7.09 (1H), 7.46 - 7.70 (8H), 7.94 (1H) , 8.22 (1H), ppt.

Example 208 (85)-M-cyclopropyl-2-methyl-4-(6-(1-methyl-1H-pyrazol-5-yl)-8-(3,3,3-trifluoro-2-hydroxypropyl) amino|imidazo|(1,2-b|pyridazine-3-ilybenzamide

E E

E E

Ro and

MN MN

Fe dna sim / - -5 zy z /

H

; We; "in (in the bush (v

The title compound was prepared according to the procedure described in Example 211 using (K5)-4-(6-chloro-8-((3,3,3-trifluoro-2-hydroxypropyl)amino|imidazo

P,2-5-Ipyridazin-3-yl)y-N-cyclopropyl-2-methylbenzamide, which was obtained according to Example 205. 1H-NMR (0M50-αb): 0-0.48-0.67 (4H), 2 ,36 (ZH), 2.80 (1H), 3.47 (1H), 3.58 (1H), 4.32 (1H), 6.58 (2H), 6.90 (1H), 7, 37 (1H), 7.48 (1H), 7.51 (1H), 7.91-8.00 (H), 8.29 (1H), m.p.

Example 209

M-cyclopropyl-4-/6-((3-fluorophenyl)sulfanyl|-8-((3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2- methylbenzamide in in U

Mn MN sy zmu -- same E vi u no no yu b b

The title compound was prepared by the procedure described in Example 194 using 4-(6-chloro-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)" M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 10a. 1H-NMR (OM50-46): b- 0.49-0.66 (4H), 2.20 (3H), 2.53-2 .70 (4H), 2.78 (1H), 3.54 (2H), 6.20 (1), 7.12 (1H), 7.34 (1H), 7.43 - 7.71 (6H ), 7.95 (1H), 8.23 (1H), mp.

Example 210

M-cyclopropyl-4-(6-C2-(diethylamino)ethyl|sulfanyl)-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)-2 -methylbenzamide v. ve

In the RU

MN MN

5 -- I sha: zm ; these

The title compound was prepared by the procedure described in Example 194 using 4-(6-chloro-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)" M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 10a 1H-NMR (0M50-ab): 0- 0.50 (2H), 0.65 (2H), 0.86 (6H), 2, 36 (ЗН), 2.59-2.71 (4Н), 2.79 (1Н), 3.23 - 3.33 (multiple Н, intersects with the peak of water), 3.54 (2Н), 6.13 (1H), 7.32 (1H), 7.52 (1H), 7.91 (1H), 7.95 (1H), 8.02 (1H) 8.28 (1H), mp.

Example 211

M-cyclopropyl-4-[8-((3-hydroxypropyl)amino1|-6-(1-methyl-1H-pyrazol-5-yl)imidazo|1,2-b|Ipyridazin-3-yl)y- 2-methylbenzamidon on on u, z, uFoche sim / nsh F zm /

MM shchi shchi

To a mixture of 51 mg (128 μmol) of 4-(6-chloro-8-((3-hydroxypropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained similarly to Example 205, using 3-hydroxy-n-propylamine, 80 mg (380 μmol) 1-methyl-1H-pyrazol-5-yl)boronic acid rapeseed, 18 mg of tetrakis(triphenylphosphine)palladium in 1 ml of ethanol and 1 ml of toluene, 0.27 ml of 10 95 aqueous sodium bicarbonate solution was added, and the mixture was stirred at 120 C for 2 hours under microwave irradiation. Then water and ethyl acetate were added, and the organic layer was washed with water and brine, concentrated and treated with dichloromethane. The residual insoluble solid gave 25 mg of the title compound. (1H), 3.41 - 3.51 (4H), 6.47 (1H), 6.88 (1H), 7.36 (1H), 7.51 (1H), 7.62 (1H), 7.91 - 7.97 (HN), (1H), 8.29 (1H), mp.

Example 212

M-cyclopropyl-2-methyl-4-(6-(phenylsulfonyl)-8-((3,3,3-trifluoropropyl)amino-imidazo|1,2-b|Ipyridazin-3-yl)benzamide

And more

In U

MN MN

Fee s Fee k v / 75 zm / o 5

U o U o 50 mg (98 μmol) M-cyclopropyl-2-methyl-4-(6-(phenylsulfanyl)-8-K3,3,3-trifluoropropyl)amino|imidazo(1,2-b|pyridazine-3Z -ilibenzamide, which was obtained according to

Example 207 was converted similarly to Example 18, obtaining after treatment and purification 30.2 mg (57 95) of the title compound. 1H-NMR (0M5O-46): 6- 0.51 (2H), 0.67 (2H), 2.31 (ZH), 2.70 (2H), 2.81 (1H), 3.29 ( 2H), 6.81 (1), 7.28 (1H), 7.65-7.82 (5H), 8.03 (1H), 8.06 (1H), 8.15 (1H), 8 .30 (1H), 8.96 (1H) ppt.

Example 213 4-I(I6-(5-Cyanopyridin-3-yl)-8-(isobutylamino)imidazo(1,2-B|Ipyridazin-Z-yl|-

M-cyclopropyl-2-methylbenzamide

Fo la

SI z / M Y zm / "kh

M u o U o 200 mg (503 μmol) of 4-(b-chloro-8-(isobutylamino)imidazo|1,2-BI pyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 194a, converted similarly to Example 202, using

B-cyanopyridine-3-ylboronic acid, with the receipt after treatment and purification of 80.9 mg (33 95) of the title compound.

1H-NMR (0M5O-46): b- 0.51 (2H), 0.62 (2H), 0.92 (6H), 2.04 (1H), 2.39 (ZH), 2.81 ( 1Н), 3.26 (2Н), 6.83 (1Н), 7.41 (1Н), 7.76 (1Н), 8.01 - 8.10 (ЗН), 8.30 (1Н), 8 .93 (1H), 9.10 (1H), 9.49 (1H), mp.

Example 214

M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-(phenylsulfanyl)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamidon on kw o . si zy Y v mi Y

U o U o 100 mg (242 μmol) 4-(6b-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 55 using benzenethiol to give, after work-up and purification, 113.5 mg (96 95) of the title compound. 1H-NMR (0M5O-46): b- 0 .49 (2H), 0.65 (2H), 1.11 (6H), 2.19 (ZH), 2.79 (1H), 3.21 (2H), 4.71 (1H), 6, 23 (1H), 6.97 (1H), 7.08 (1H), 7.44-7.52 (ЗН), 7.58-7.65 (ЗН), 7.70 (1Н), 7, 93 (1H), 8.22 (1H) ppt.

Example 215

M-cyclopropyl-2-methyl-4-(6-P2-(morpholin-4-yl)/ethyl|sulfanyl)-8-|(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b |pyridazin-3-yl)benzamid schi EII

In U

MN MN with M and M

Dt M kit zni

U o U o 100 mg (228 μmol) 4-16-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was prepared according to Intermediate Example 10a, was converted analogously to Example 55 using 2-(morpholin-4-yl)ethanethiol to give, after work-up and purification, 78.2 mg (59 95) of the title compound. NMR (0М50-46): b- 0.49 (2Н), 0.65 (2Н), 2.30-2.39 (4Н), 2.37 (ЗН), 2.57-2.71 (4Н ), 2.80 (1), 3.28 (2H), 3.47-3.57 (6H), 6.13 (1H), 7.33 (1H), 7.53 (1H), 7, 90 (1H), 7.96 (1H), 7.98 (1H), 8.29 (IN) ppt.

Example 216 (85)-M-cyclopropyl-4-/6-((3-fluorophenyl)sulfanyl|-8-((3,3,3-trifluoro-2-hydroxypropyl)amino|imidazo|1,2-5| pyridazin-3-yl-2-methylbenzamide

E E

Oh, oh, oh, oh, oh, oh, oh, oh, oh!

MN MN si zi s vi

In o in o

95 MG (191 μMOL) (85)-4-(6-chloro-8-((3,3,3-trifluoro-2-hydroxypropyl)amino|imidazo|1,2-5|pyridazin-3-yl)" M-Cyclopropyl-2-methylbenzamide obtained according to Intermediate Example 205 was converted analogously to Example 194 using 3-fluorobenzenethiol to give after work-up and purification 54 mg (49 95) of the title compound. 1H-NMR (0M50-46) : b- 0.49 (2H), 0.65 (2H), 2.20 (ZH), 2.79 (1H), 3.45 -3.62 (2H), 4.26 (1H), 6 .24 (1H), 6.56 (1H), 7.13 (1H), 7.35 (1H), 7.50 (1H), 7.51 - 7.56 (ZH), 7.65 (1H ), 7.71 (1H), 7.97 (IN), 8.25 (1H), mp.

Example 217

M-cyclopropyl-4-(6-((3,3-dimethylbutyl)sulfanyl-8-|((2-hydroxy-2-methylpropyl)amino|imidase oP,2-b|pyridazin-3-yl-g-methylbenzamide he he

Today is 5 Bl we;

U o U o 75 mg (181 μmol) 4-(6-chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)u"M-cyclopropyl -2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51 using 3,33-dimethylbutane-1-thiol, to give after work-up and purification 29.2 mg (31 95) of the title compound. NMR (0M50O-ab): b- 0.49 (2Н), 0.65 (2Н), 0.89 (9Н), 1.13 (6Н), 1.54 (2Н), 2.35 (ЗН) , 2.79 (1), 3.13 (2H), 5.21 (2H), 4.72 (1H), 6.17 (1H), 6.81 (1), 7.29 (1H), 7.91 (1H), 7.98 (1H), 7.99 (1H), 8.28 (1H) ppt.

Example 218

M-cyclopropyl-4-16-(2,6-difluorophenyl)sulfanyl)|-8-K2-hydroxy-2-methylpropyl)amino|imidazo(1,2-5|pyridazin-3-yl)y-2-methylbenzamide he he

Fe se sizyy Fe ze

E u o u o 75 mg (181 μmol) 4-(6-chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl -2-methylbenzamide, which was prepared according to Intermediate Example 7a, was converted analogously to Example 51 using 2,6-difluorobenzenethiol to give, after work-up and purification, 6.5 mg (6 95) of the title compound. : 6- 0.63 (2Н), 0.89 (2Н), 1.40 (6Н), 2.33 (ЗН), 2.91 (1Н), 3.29 (2Н), 5.96 (1Н ), 6.05 (1Н), 6.55 (1Н), 7.00-7.11 (ЗН), 7.41-7.53 (ЗН), 7.57 (1Н) ppt.

Example 219

M-cyclopropyl-4-[6-((3-fluorophenyl)sulfanyl|-8-((3,3,3-trifluoropropyl)amino)imidazo|(1,2-b|Ipyridazin-3-yl-3-hydroxybenzamide

Yi I

In the RU

MN MN still dh so sa and dsh- in you on

U o U o 75 mg (165 μmol) 4-(6b-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl- The 3-methoxybenzamide prepared according to Intermediate 52a was converted analogously to Intermediate 51 using 3-fluorobenzenethiol to give, after work-up and purification, 24.0 mg (27 95) of the title compound.1H-NMR (0M5O-46) : b- 0.54 (2Н), 0.66 (2Н), 2.60 (2Н), 2.80 (1Н), 3.52 (2Н), 6.13 (1Н), 7.07 (1 ), 7.28 (1H), 7.34 (1H), 7.38-7.53 (ZH), 7.71 (1H), 7.85 (1H), 7.94 (1H), 8, 34 (IN), 10.12 (1H) ppt.

Example 220

M-cyclopropyl-4-[6-(2-(hydroxymethyl)phenyl|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamide he he

Foche gu im y si mi / -- zhk M on

N

M (in (in) M in 5.25 g (12.7 mmol) 4-(6-chloro-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazine-3 - yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 1, using (2-(hydroxymethyl)phenyl|boronic acid, obtaining after treatment and purification 4.90 g (80 95 ) of the title compound. 1H-NMR (0M50O-ab): b- 0.51 (2H), 0.66 (2H), 1.18 (6H), 2.36 (3H), 2.82 (1H ), 3.32 (2H), 4.66 (2H), 4.75 (1H), 5.13 (1H), 6.45 (1H), 6.95 (1H), 7.35 (1H) , 7.39 (1H), 7.45-7.52 (2H), 7.66 (1H), 7.95 (IN), 8.00 (1H), 8.01 (1H), 8.26 (1H) ppt.

Example 221 4-6-(2E)-but-2-en-2-ylI|-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-B1 pyridazin-3-yl)u" -M-cyclopropyl-2-methylbenzamide and i

In U

MN MN

fo la)

SI zm ) - I zm ) oi oi 115 mg (262 μmol) 4-16-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl) "M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 10a, was converted analogously to Example 1, using (22)-but-2-en-2-ylboronic acid, obtaining after treatment and purification 7.2 mg (6 95) of the title compound. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.65 (2H), 1.84 (ЗН), 2.07 (ЗН), 2.36 ( ЗН), 2.67 (2Н), 2.80 (1), 3.61 (2Н), 6.43 (1Н), 6.49 (1Н), 7.32 (1Н), 7.35 (1Н ), 7.97 (1H), 8.03 (1H), 8.07 (1H), 8.27 (1H) ppt.

Example 222

M-cyclopropyl-4-76-(2-(fluoromethyl)phenyl|-8-K2-hydroxy-2-methylpropyl)

amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamide ev) on che ss zy 7 zim 4 on E

In o In o

To the solution 329 MG (677 μmol) M-cyclopropyl-4-(6-(2-(hydroxymethyl)phenyl|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazine-3- 98 μl of 1.2-methylbenzamide, which was obtained according to Example 220, was added to 13 ml of dichloromethane at 3 "C

M-ethyl-M-(trifluoro-A-4-sulfanyl)ethanamine. After stirring for 10 min, the solution was poured into water and the aqueous phase was extracted with dichloromethane. The combined organic phases were washed with sodium bicarbonate solution and dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to give 28.6 mg (8 Fo) of the title compound. 1H-NMR (SOSIS): 6- 0.61 (2H), 0.87 (2H), 1.47 (6H), 2.48 (ZH), 2.90 (1H), 3.36 (2H) , 5.21 (1H), 5.58 (2H), 5.97 (1H), 6.26 (1H), 6.71 (1H), 7.37 (1H), 7.46 (1H), 7.51 (1H), 7.58 (1H), 7.64 (1H), 7.74 (1H), 7.81 (1H), 7.88 (1H) mp.

Example 223

M-cyclopropyl-4-16-(2-methoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide

And I

In U

MN MN you know him

U o U o 150 mg (343 μmol) 4-(b-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)u"M-cyclopropyl -2-methylbenzamide, which was obtained according to Intermediate Example 10a, was converted analogously to Example 51 using 2-methoxyphenol to give, after work-up and purification, 8.1 mg (5 95) of the title compound. 1H-NMR (SOSIS): b - 0.60 (2H), 0.88 (2H), 2.26 (ЗН), 2.57 (2Н), 2.89 (1Н), 3.68 (2Н), 3.78 (ЗН), 5.82 (1H), 5.94 (1H), 5.98 (1H), 7.01 (1H), 7.05 (1H), 7.18 (1H), 7.22 (1H), 7 .27 (1H), 7.55 (1H), 7.70 (IN), 7.72 (1H) ppt.

Example 224

M-cyclopropyl-4-16-((2-hydroxyphenyl)sulfanyl|-8-((3,3,3-trifluoropropyl)amino|imidazoi|1,2-BI pyridazin-3-yl)-2-methylbenzamide

E E

E E

In U

MN MN si zu you sho

M M all 100 mg (228 μmol) 4-16-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl- 2-methylbenzamide, which was obtained according to Intermediate Example 10a,

was converted similarly to Example 51, using 2-methoxybenzenethiol, to obtain after treatment and purification 5.1 mg (4 95) of the title compound. 1H-NMR (0M5O-46): b- 0.49 (2H), 0.65 (2H), 2.21 (3H), 2.59 (2H), 2.79 (1H), 3.49 ( 2H), 6.05 (IN), 6.687 (1H), 6.98 (1H), 7.07 (1H), 7.34 (1H), 7.46 (1H), 7.56 (1H), 7.67 (1H), 7.72 (1H), 7.93 (1H), 8.23 (1H), 9.96 (1H) ppt.

Example 225

M-cyclopropyl-4-76-(3-methoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide

E.E.E.E.E

In U

MN MN sy zu ---- oz 7

U o U o 150 mg (343 μmol) 4-16-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was prepared according to Intermediate Example 10a, was converted analogously to Example 51 using 3-methoxyphenol to give, after work-up and purification, 5.1 mg (C 95) of the title compound. 0.60 (2H), 0.87 (2H), 2.31 (ZH), 2.56 (2H), 2.89 (1H), 3.66 (2H), 3.80 (ZH), 5 .85 (1H), 5.88 (1H), 6.03 (1H), 6.79-6.88 (ZH), 7.24 (1H), 7.33 (1H), 7.63 (1H ), 7.73 (1H), 7.79 (1H) ppt.

Example 226

M-cyclopropyl-4-16-((3,3-dimethylbutyl)sulfanyl|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y). 2-methylbenzamide

B in

In U

MN MN sim" / vm /

M A M

(c) (c) h b b 100 mg (228 μmol) 4-16-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl) "M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 10a, was converted analogously to Example 51, using 3,3-dimethylbutane-1-thiol, to obtain after work-up and purification 3.6 mg (C 95) indicated in the title compounds. 1H-NMR (SOSIS): b- 0.63 (2H), 0.90 (2H), 0.94 (9H), 1.62 (2H), 2.51 (ЗН), 2.52 ( 2H), 2.92 (1H), 3.19 (2H), 3.61 (2H), 5.84-5.93 (ЗН), 7.37 (1H), 7.69 (1H), 7 .88 (1H), 7.91 (1H) ppt.

Example 227

M-cyclopropyl-4-16-((4-methoxyphenyl)sulfanyl|)|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y. 2-methylbenzamide

And I

In U

MN MN sim" / -ny vm /

M » M c) - c) vo b b

100 mg (228 μmol) 4-16-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 10a, was converted analogously to Example 51 using 4-methoxybenzenethiol to give after work-up and purification 16.8 mg (13 95) of the title compound. 2H), 0.90 (2H), 2.40 (ZH), 2.47 (2H), 2.92 (1H), 3.57 (2H), 3.88 (ZH), 5.82-5 .93 (ZH), 6.98 (2H), 7.17 (1H), 7.54-7.63 (4H), 7.69 (1H) ppt.

Example 228

M-cyclopropyl-2-methyl-4-16-(pyridin-4-yl)-8-((3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)benzamide ve in

In U

MN MN se dna M

SI zm / --skk s Y zm /

Swing

M M

(c) (c) u b b 250 mg (571 μmol) 4-/6-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl )"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 10a, was converted analogously to Example 1 using pyridine-4-ylboronic acid, obtaining after treatment and purification 6.7 mg (2 95) of the title compound. 1H-NMR (SOSIS): 6- 0.63 (2H), 0.89 (2H), 2.53 (ZH), 2.61 (2H), 2.91 (1H), 3.72 (2H) , 6.20 (1H), 6.43 (1H), 6.67 (1H), 7.44 (1H), 7.80 (1H), 7.82 (2H), 7.89 (1H), 7.96 (1H), 8.72 (2H) ppt.

Example 229 (85)-M-cyclopropyl-4-I6-(4-fluorophenyl)-8--(4-methylmorpholin-2-yl)methyl amino)imidazo(1,2-b|Ipyridazin-3-yl|- 2-methylbenzamide ve ve x x

MN MN

Fo Dnya sizim and syu zim 7

E neono 2 ih b 50 MG (110 μMOL) (85)-4-Ib6-chloro-8-0((25)-4-methylmorpholin-2-yl|methyl)amino)imidazo(1,2-b| Ipyridazin-3-yl|-N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 56ba, was converted analogously to Example 1, using (4-fluorophenyl)boronic acid, obtaining after work-up and purification 12.2 mg (22 95) of the title compound. 1H-NMR (0M50-a6): 0- 0.51 (2H), 0.66 (2H), 1.80 (1H), 1.96 (1H), 2.14 ( ЗН), 2.39 (ЗН), 2.54 (1), 2.74 (1Н), 2.81 (1Н), 3.45-3.55 (ЗН), 3.72-3.80 ( 2H), 6.72 (1H), 7.34 (2H), 7.39 (2H), 8.00 (1H), 8.03 (1H), 8.06-8.12 (ZH), 8 ,30 (1H), ppt.

Example 230

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-4-yl)imidazo

P,2-Shipyridazin-3-yl)u-2-methylbenzamidon s zm / -- her zm /

Swing

M M all 200 mg (483 μmol) 4-(6b-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 1 using pyridine-4-ylboronic acid, 3 yielding after work-up and purification 28.3 mg (12 95) of the title compound. 1H-NMR (0M50O- ab): b- 0.69 (2Н), 0.91 (2Н), 1.49 (6Н), 2.46 (ЗН), 2.96 (1Н), 3.33 (2Н), 4.99 (1H), 6.23 (1H), 6.53 (1H), 6.58 (1H), 7.29 (1H), 7.66 (2H), 7.70 (1H), 7.76 ( 1H), 7.82 (1H), 8.57 (2H) ppt.

Example 231

M-cyclopropyl-2-methyl-4-16-(methylsulfanyl)-8-T2-(morpholin-4-ylsulfonyl)ethylamino)imidazo|1,2-5|pyridazin-3-yl|renzamide (in (in) c s "5 "5 (in (in ich ich - sati yu zvy

U o U o 46 MG (89 μmol) 4-(6-chloro-8-P2-(morpholin-4-ylsulfonyl)ethyl|amino)imidazo|1,2-b|Ipyridazin-3-yl)-M-cyclopropyl - 2-methylbenzamide, which was obtained according to Intermediate Example 231a, was converted analogously to Example 51, using sodium methanethiolate to obtain, after treatment and purification, 12 mg (25 95) of the title compound. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.65 (2H), 2.36 (ЗН), 2.57 (ЗН), 2.80 (1Н), 3.14 ( 4H), 3.44 (2H), 3.60 (4H), 3.69 (2H), 6.15 (1H), 7.35 (1H), 7.43 (1H), 7.93 (1H ), 7.98 (1H), 8.06 (1H), 8.28 (1H) ppt.

Intermediate Example 231a 4-(6-chloro-8-P2-(morpholin-4-ylsulfonyl)ethyl|amino)imidazo|1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide (in ) (in what "5

S 9 og I o se me She, s more,

AND

In about 650 MG (1.38 mmol) of b-chloro-3-iodo-M-(2-(morpholin-4-ylsulfonyl)ethylimidazo(1,2-b|Ipyridazin-8-amine), which was obtained according to the Intermediate Example 2316, converted similarly to Intermediate

Example 1a, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, obtaining after treatment and purification 102 mg (14 Fo ) of the title compound.

Intermediate Example 2316 b-chloro-3-iodo-M-(2-(morpholin-4-ylsulfonyl)ethylimidazo|1,2-5b|pyridazin-8-amine sa

Vg og 2 1 du - M, sati

Fe

SI zi! 1.00 g (2.79 mmol) of 8-bromo-6b-chloro-3-iodoimidazo|1,2-b|Ipyridazine, which was obtained according to

Intermediate Example 1c was converted similarly to Intermediate Example 1, using 2-(morpholin-4-ylsulfonyl)ethanamine to obtain after treatment and purification 650 mg (49 90) of the title compound.

Example 232

M-cyclopropyl-4-76-(4-fluoro-2-methylphenyl)-8-((2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2 -methylbenzamide - -

MN MN

Fo days sim 7 winters and

IS

U o U o 100 mg (242 μmol) 4-(6b-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 1 using (4-fluoro-2-methylphenyl)boronic acid to give after work-up and purification 19.0 mg (15 95) of the title compound. NMR (0M5O-46): 6- 0.47 (2H), 0.64 (2H), 1.15 (6H), 2.33 (ZH), 2.38 (ZH), 2.78 (1H) , 3.31 (2H), 4.71 (1H), 6.36 (1H), 6.95 (1H), 7.12 (1H), 7.19 (1H), 7.32 (1H), 7.47 (1H), 7.92 (1H), 7.98 (1H), 7.99 (1H), 8.24 (1H) ppt.

Example 233

M-cyclopropyl-4-(6-(2-fluorophenyl)-8-(2-hydroxy-2-methylpropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide

MN MN se la)

SI zm / in zm /

100 mg (242 μmol) of 4-(6β-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-β|Ipyridazin-3-yl)"M -cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 1 using (2-fluorophenyl)boronic acid to give, after work-up and purification, 10.0 mg (8 95) of the title compound. NMR (0М5О-46): b- 0.49 (2Н), 0.64 (2Н), 1.16 (6Н), 2.36 (ЗН), 2.79 (1Н), 3.31 (2Н) , 4.74 (1H), 6.57 (1H), 7.00 (1H), 7.31-7.40 (ZH), 7.52 (1H), 7.78 (1H), 8.01 (1H), 8.03 (1H), 8.06 (1H), 8.26 (IN) ppt.

Example 234

4-16-(5-cyanopyridin-3-yl)-8-(2-hydroxy-2-methylpropyl)amino|imidazo(|1,2-BI pyridazin-3-yl)y"-M-cyclopropyl-2- methylbenzamide in u

MN MN se la) s zm / ; MU | zm /

Sh,

See

U o U o 200 mg (483 μmol) 4-(6b-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was prepared according to Intermediate Example 7a, was converted analogously to Example 1 using (5-cyanopyridin-3-yl)boronic acid to give, after work-up and purification, 19.0 mg (8 95) of the title compound. 1H -NMR (0М5О-46): b- 0.51 (2Н), 0.66 (2Н), 1.19 (6Н), 2.39 (ЗН), 2.81 (1Н), 3.42 (2Н ), 4.79 (1), 6.96 (1H), 7.08 (1H), 7.41 (1H), 8.01 (1H), 8.04 (1H), 8.10 (1H) , 8.91 (1H), 8.91 (1H), 9.11 (1H), 109.50 (1H) ppt.

Example 235

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl|imidazo(1,2-b |Ipyridazin-3-yl)u.2-methylbenzamide in u

MN MN se la) s miy Y and se zy Y

E MM

In o u o 100 mg (242 μmol) 4-(6b-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)u"M-cyclopropyl- 2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted similarly to Example 1, using

PP -methyl-3-"(trifluoromethyl)-1H-pyrazole-5-yl!boronic acid, obtaining after processing and purification 25 mg (1995) of the title compound. 1H-NMR (0M5O-ab): b- 0.50 (2H), 0.65 (2H), 1.17 (6H), 2.36 (ZH), 2.80 (1H), 3.37 ( 2H), 4.22 (ZH), 4.77 (1H), 6.73 (1H), 7.07 (1H), 7.37 (1H), 7.46 (1H), 7.91 (1H ), 7.94 (1H), 8.00 (1H), 8.30 (1H) ppt.

Example 236 (85)-4-(6-(cyclohex-1-en-1-yl)-8-((3,3,3-trifluoro-2-hydroxypropyl)amino)imidazo|1,2-b|Ipyridazine -3-yl)-N-cyclopropyl-2-methylbenzamide

E E

E E ver or

MN MN

Fo dn M s zm y - -- zm /

U o U o 85 MG (187 μMOL) (85)-4-(6-chloro-8-((3,3,3-trifluoro-2-hydroxypropyl)amino|imidazo|1,2-5|pyridazine-3 - yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Example 205, was converted similarly to Intermediate Example 1, using cyclohex-1-en-1-ylboronic acid, obtaining after treatment and purification 4.0 mg (4 95) of the title compound. 1H-NMR (0M5O-46): b- 0.48 (2H), 0.62 (2H), 1.58 (2H), 1.68 (2H), 2.20 (2H) , 2.34 (ZH), 2.49 (2H), 2.77 (1H), 3.48 (1H), 3.64 (1H), 4.28 (1H), 6.46 (1H), 6.54 (1H), 6.65 (1H), 7.05 (1H), 7.33 (1H), 7.94 (1H), 8.01 (1H), 8.02 (1H), 8 .23 (1H) ppt.

Example 237

M-cyclopropyl-2-methyl-4-18-((1-methyl-1 H-pyrazol-5-yl)umethyl|amino)-6-(methylsulfanyl)imidazo|1,2-b|pyridazin-3-yl |benzamide

Mi Mi o o

MN MN sit zvu

U o U o 100 MG (229 μMOL) 4-(6-chloro-8-1(1-methyl-1H-pyrazol-5-yl)umethyl|amino)imidazo|(1,2-b|Ipyridazin-3- yl)-N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 237a, was converted analogously to Example 51 using sodium methanethiolate to give after treatment and purification 75 mg (72 95) of the title compound. 1H-NMR (0M5O-46): b- 0.49 (2H), 0.65 (2H), 2.35 (ZH), 2.53 (ZH), 2.80 (1H), 3.79 ( ЗН), 4.58 (2Н), 6.14 (2Н), 7.25 (1Н), 7.34 (1Н), 7.92-8.02 (ЗН), 8.05 (1Н), 8 .28 (1H) ppt.

Intermediate Example 237a 4-(6-chloro-8-1(1-methyl-1H-pyrazol-5-yl)umethylamino)imidazo|1,2-b|pyridazin-3-yl)-M-cyclopropyl-2 -methylbenzamide

Mi-- what

Met MN

MN --» sim si zy

500 MG (1.29 mmol) b-chloro-3-iodo-M-(1-methyl-1H-pyrazol-5-yl)methylimidazo(1,2-b|Ipyridazin-8-amine, which was obtained according to Intermediate Example 2376, was converted similarly to Intermediate

Example 1a, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)/ibenzamide with the result after treatment and purification of 277 mg (47 Fo ) of the title compound.

Intermediate Example 2375 b-chloro-3-iodo-M-(1-methyl-1H-pyrazol-5-yl)methylimidazo(1,2-b|pyridazin-8-amine

M-g

Wed o Sat Fe

And x s m-f zo! 1.00 g (2.79 mmol) of 8-bromo-6b-chloro-3-iodoimidazo|1,2-b|Ipyridazine, which was obtained according to

Intermediate Example 1c was converted similarly to Intermediate Example 16, using 1-(1-methyl-1H-pyrazol-5-ylumethanamine) to obtain, after treatment and purification, 1.00 g (92 95) of the title compound.

Example 238

M-cyclopropyl-4-16-|(3-hydroxyphenyl)sulfanyl|-8-((3,3,3-trifluoropropyl)amino|imidazoi|1,2-BI pyridazin-3-yl)-2-methylbenzamide

E E

E E

In U

MH MH sim" / sha 57" / r louse: oi oi 100 mg (228 μmol) 4-16-chloro-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazine -3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 10a, was converted analogously to Example 51, using 3-methoxybenzenethiol, obtaining after treatment and purification 68 mg (65 95) of the title compound. 1H - NMR (0M5O-46): b- 0.49 (2H), 0.65 (2H), 2.23 (3H), 2.60 (2H), 2.79 (1H), 3.52 (2H ), 6.11 (1H), 6.86 (1H), 6.98 (1H), 7.01 (1H), 7.15 (1H), 7.26 (1H), 7.63 (1H) , 7.73 (1H), 7.74 (1H), 7.94 (1H), 8.21 (1H), 9.69 (1H) ppt.

Example 239

M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-H2-(morpholin-4-yl) ethyl|sulfanyl)imidazo|1,2-b|Ipyridazin-3-yl )-2-methylbenzamide on on

Fe / Fo vm / TCHU-k r zm / ih re and ih r

He) and C 6) its 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M -cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51, using 2-(morpholin-4-yl)ethanethiol, obtaining after treatment and purification 45.4 mg (50 95) of the title compound . , 2.61 (2H), 2.80 (1H), 3.22 (2H), 3.27 (2H), 3.51 (4H), 4.71 (1H), 6.18 (1H), 6.81 (1H), 7.33 (1H), 7.89 (1H), 7.96 (1H), 7.98 (1H), 8.28 (1H) ppt.

Example 240 (85)-M-cyclopropyl-4-16-(2,2-difluorocyclopropyl)methoxy1|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazine-3- yl)y-2-methylbenzamido on on

Pho Pho sim" / about /

M what M still 325 mg (785 μmol) 4-(6-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b|pyridazin-3-yl)"M-cyclopropyl -2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted similarly to Example 51, using

I185)-2,2-difluorocyclopropyl|methanol to obtain after processing and purification 12.3 mg (C95) of the title compound. 1H-NMR (SOSIS): 6- 0.64 (2H), 0.89 (2H), 1.29 (IN), 1.43 (6H), 1.56 (1H), 2.15 (1H) , 2.49 (ZH), 2.92 (1H), 3.27 (2H), 4.34 (2H), 4.78 (1H), 5.70 (1H), 6.01 (1H), 6.42 (1H), 7.38 (1H), 7.60 (1H), 7.80 (1H), 7.83 (1H) ppt.

Example 241

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(2,2,3,3-tetrafluoro-4-hydroxybutoxy)imidazo|1,2-b|Ipyridazine-3 -yl)y-2-methylbenzamide (A) and

M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino|-6-41E)-2,3,3-trifluoro-4-hydroxybut-1-en-1-yl|oxy)imidazo (1,2-b|pyridazin-3-yl)-2-methylbenzamidon ve t МН МН

MN

Ms. Ste sa

Fe Fe, Fe Fe,

The fairy is E

SIME TV) in Nky

E E r b-E i

M (c) (c) oi A M V M 250 mg (604 μmol) 4-(6b-chloro-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|Ipyridazine-3 -yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 7a, was converted analogously to Example 51, using 2,2,3,3-tetrafluorobutane-1,4-diol, to obtain after treatment and purification 38, 3 mg (12 95) of the title compound A and 88.7 mg (28 Fo) of the title compound B. 1H-NMR (0M50O-ab) of A: b- 0.50 (2H), 0.65 ( 2H), 1.14 (6H), 2.35 (ZH), 2.80 (1H), 3.26 (2H), 3.90 (2H), 4.71 (1H), 4.89 (2H ), 6.01 (2H), 6.89 (1H), 7.33 (1H), 7.90 (1H), 7.93 (1H), 7.97 (1H), 7.28 (IN) mp 1H-NMR (0M5O-46) and B: b- 0.50 (2H), 0.65 (2H), 1.14 (6H), 2.35 (ZH), 2.80 (1H), 3.26 (2H), 3.85 (2H), 4.70 (1H), 5.93 (1H), 6.18 (1H), 7.17 (1H), 7.33 (1H), 7 .70 (1H), 7.89 (1H), 7.96 (1H), 8.02 (IN), 8.29 (1H) ppt.

Example 242

M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-14-"trifluoromethyl)phenyl|sulfanyl)imidazo|1,2-b|pyridazin-3-yl)-2- methylbenzamid on on ve / in / (in z. (in ni ni

B OH

50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 4-(trifluoromethyl)benzenethiol to give after work-up and purification 23 mg (36 95) of the title compound.1H-NMR (0M5O-46): 6- 0 .47 (2H), 0.65 (2H), 1.13 (6H), 2.17 (ZH), 2.78 (1H), 3.25 (2H), 4.70 (1), 6, 37 (1H), 7.04-7.10 (2H), 7.59 (1H), 7.69 (1H), 7.79 (4H), 7.95 (1H), 8.18 (1H) ppt

Example 243

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-phenoxyimidazo

P,2-Shipyridazin-3-yl benzenecarbothioamid it is not chn

MN M se /Fya / zi - -- om" zu y o o U

127 mg (316 μmol) of 4-18-K2-hydroxy-2-methylpropyl)amino|-6-phenoxyimidazo 1,2-b|pyridazine-3-ylbenzaldehyde, which was obtained according to Intermediate Example 243a, was converted similarly to Example 13 to obtain after treatment and purification 47 mg (30 95) of the title compound. 1H-NMR (0M5O-avb): 0- 0.71-0.87 (4H), 1.16 (6H), 3.26 (2H), 3.41 (1H), 4.72 (1H), 6.16 (1H), 6.99 (1H), 7.21-7.30 (ZH), 7.44 (2H), 7.57 (2H), 7.91 (2H), 7.99 ( 1H), 10.05 (1H) ppt.

Intermediate Example 24Za 4-18-K2-hydroxy-2-methylpropyl)amino|-6-phenoxyimidazo|(1,2-5B|Ipyridazin-3-yl)benzaldehyde g on /Ffya ; 152 mg (340 μmol) 1-(13-(4-(1,3-dioxolan-2-yl)/phenyl|-6-phenoxyimidazo|(1,2-b|Ipyridazine -8-ylamino)-2-methylpropan-2-ol, which was obtained according to Intermediate Example 2436, was converted analogously to Intermediate Example 13a, obtaining after treatment and purification 132 mg (96 95) of the title compound.

Intermediate Example 2435 1-(13-(4-(1,3-dioxolan-2-yl)uphenyl|-6-phenoxyimidazo|1,2-b|pyridazin-8-yl)iamino)-2-methylpropan-2- ol he he still | o si zm /Y DU Y fi; 07 250 mg (643 μmol) 1-((b-chloro-3-(4-(1,3-dioxolan-2-yl)phenylimidazo|(1,2-b|Ipyridazine-8-ylamino)-2-methylpropane) -2-ol, which was obtained according to Intermediate Example 32c, was converted analogously to Example 51 using phenol to give, after treatment and purification, 157 mg (55 95) of the title compound.

Example 244

M-cyclopropyl-4-76-(3-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino)imidazo|1,2-b|Ipyridazin-3-ylbenzenecarbothioamidon is not che

MN m /Fo /Fya ; with M-Y with 2-Y - -- om om g" F Y is M g (c)

b

79 MG (188 μMOL) of 4-(6-(3-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)benzaldehyde, which was obtained according to Intermediate Example 244a was converted analogously to Example 13, obtaining after treatment and purification 22 mg (22 95) of the title compound. 1H-NMR (0M5O-ab): 6- 0.72-0.86 (4H), 1.15 (6H), 3.41 (2H), 3.49 (1H), 4.72 (1H), 6.18 (1H), 7.03-7.15 (ZH), 7.21 (1H), 7.47 (1H), 7.60 (2H), 7.92 (2H), 8.00 ( IN), 10.07 (1H) ppt.

Intermediate Example 244a

4-(6-(3-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-BI pyridazine-3-ylbenzaldehyde

ОН on ob / om" 4 g 5 di b

He) and 92 MG (198 μMOL) 1-(13-I4-(1,3-dioxolan-2-yl)uphenyl|-6-(3-fluorophenoxy)imidazo|1,2-b|Ipyridazine-8- ilyamino )-2-methylpropan-2-ol, which was obtained according to Intermediate Example 2446, was converted analogously to Intermediate Example 13a, obtaining after treatment and purification 80 mg (96 95) of the title compound.

Intermediate Example 244p 1-(13-(4-(1,3-dioxolan-2-yl)uphenyl|-6-(3-fluorophenoxy)imidazo|1,2-b|Ipyridazin-8-yl)iamino)-2 -methylpropan-2-olone onsite -nsh obtm d 09 07 250 mg (643 μmol) 1-((b-chloro-3-(4-(1,3-dioxolan-2-yl)phenylimidazo|(1, 2-b|Ipyridazin-8-ylamino)-2-methylpropan-2-ol, which was obtained according to Intermediate Example 32c, was converted analogously to Example 51, using 3-fluorophenol, obtaining after treatment and purification 94.2 mg (32 95 ) of the title compound.

Example 245

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(phenylsulfanyl)imidazo|1,2-b|Ipyridazin-3-ylbenzenecarbothioamidon it is not

MN M se sia /Fe fia /

WITH

5 (105 MG (251 μMOL) of 4-18-K2-hydroxy-2-methylpropyl)amino|-6-(phenylsulfanyl)imidazo|1,2-b|pyridazin-3-yl)benzaldehyde, which was obtained according to with Intermediate Example 245a, was converted similarly to Example 13, obtaining after treatment and purification 27.3 mg (21 95) of the title compound. 1H-NMR (0M5O-avb): 6- 0.75-0.87 (4H), 1.12 (6H), 3.22 (2H), 3.43 (1H), 4.69 (1H), 6.24 (1H), 6.98 (1H), 7.46-7.59 (5H), 7.63 (2H), 7.682 (2H), 7.99 (1H), 10.07 (1H) ppt

Intermediate Example 245a 4-18-K2-hydroxy-2-methylpropyl)amino|-6-(phenylsulfanyl)imidazo|1,2-b|pyridazin-3-yl)benzaldehyde

He is not

A) With zm / ef o 155 MG (335 μMOL) 1-(13-I4-(1,3-dioxolan-2-yl)phenyl|-6-«(phenylsulfanyl)imidazo|1,2-b|pyridazine- 8-ylamino)-2-methylpropan-2-ol, which was obtained according to Intermediate Example 245rb, was converted similarly to Intermediate Example 1Za, obtaining after treatment and purification 109 mg (78 95) of the title compound.

Intermediate Example 2455 1-(13-(4-(1,3-dioxolan-2-yl)uphenyl|-6-(phenylsulfanyl)imidazo|1,2-b|pyridazin-8-yl)iamino)-2-methylpropane -2-ol on on si zym Y A / (in (in (in) (in) - - 250 mg (643 μmol) 1-((b-chloro-3-(4-(1,3-dioxolane-2 -yl)phenylimidazo|(1,2-b|Ipyridazin-8-ylamino)-2-methylpropan-2-ol, which was obtained according to Intermediate Example 32c, was converted analogously to Example 51, using benzenethiol, to give after work-up and purification 154 mg (52 95) of the title compound.

Example 246

M-cyclopropyl-4-76-((3-fluorophenyl)sulfanyl|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-ylbenzenecarbothioamidon ve ne chn

MN M ss d) /Fe, in z -- 5 M /ie y ; N

E M o U 94 MG (215 μMOL) 4-16-KZ-fluorophenyl)sulfanyl)|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl/ of benzaldehyde, which was obtained according to Intermediate Example 246ba, was converted analogously to Example 13, obtaining after treatment and purification 9.2 mg (8 95) of the title compound. .87 (4H), 1.12 (6H), 3.23 (2H), 3.44 (1H), 4.71 (1H), 6.31 (1H), 7.07 (1H), 7, 35 (1H), 7.44 (1H), 7.48-7.55 (2H), 7.58 (2H), 7.85 (2H), 8.01 (1H), 10.10 (1H) ppt

Intermediate Example 24ba 4-16-KZ-fluorophenyl)sulfanyl)|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|Ipyridazine-3-ylbenzaldehyde

ОН he you / vm 4 g 5 di b

He) and 108 MG (225 μMOL) 1-(13-14-(1,3-dioxolan-2-yl)phenyl|-6-(3-fluorophenyl)sulfanilyimidazoi|1,2-BI pyridazine-8-ylamino) -2-methylpropan-2-ol, which was obtained according to Intermediate Example 2465, was converted analogously to Intermediate Example 13a, obtaining after treatment and purification 95 mg (97 95) of the title compound.

Intermediate Example 2465 1-(13-(4-(1,3-dioxolan-2-yl)uphenyl|-6-(3-fluorophenyl)sulfanylimidazo|1,2-B)pyridazin-8-ylamino)-2-methylpropane -2-olone onsite - vid d (c) (c) (c) (c) mass - 250 mg (643 μmol) 1-((b-chloro-3-I(4-(1,3-dioxolane) -2-yl/phenylimidazo/1,2-b|pyridazin-8-ylamino)-2-methylpropan-2-ol, which was obtained according to Intermediate Example 32c, was converted analogously to Example 51, using 3-fluorobenzenethiol, to give after working up and purification of 103.2 mg (33 95) of the title compound.

Example 247

M-cyclopropyl-2-methyl-4-(6-C4-trifluoromethyl)phenyl|sulfanyl)-8-

I(3,3,3-trifluoropropyl)amino|imidazo(/1,2-b|pyridazin-3-yl)benzamide

And in

In U

50 mg (104 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo (|1,2-b|Ipyridazin-3-yl)''M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 4-(trifluoromethyl)benzenethiol, with the product after work-up and purification 20.2 mg (32.95) of the title compound. 2.87 (1H), 3.57 (2H), 5.95 (1H), 6.04 (1H), 6.54 (1H), 7.08 (1H), 7.48 (1H), 7 .55 (1H), 7.66 (2H), 7.68 (1H), 7.73 (2H) ppt.

Intermediate Example 247a 4-16-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide and

E ts i

In MN with 2 ki ak se Vg M

Weighed 1.00 g (2.3 mmol) of 6-bromo-3-iodo-M-(3,3,3-trifluoropropyl)imidazo|1,2-b|Ipyridazine-8-amine, which was obtained according to Intermediate Example 247, were converted similarly to Intermediate

Example 1a, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, which was obtained according to Intermediate Example 7b, with obtaining after processing and purification of 580 mg (52 95) of the title compound.

Intermediate Example 247B b-bromo-3-iodo-M-(3,3,3-trifluoropropyl)imidazo|1,2-b|Ipyridazin-8-amine

IS

IS

Ve U vm Fe

And with

Ve and

AND

2.30 g (5.71 mmol) of 6,8-dibromo-3-iodoimidazo(1,2-b|Ipyridazine, which was obtained according to

Intermediate Example 9bs was converted similarly to Intermediate Example 1, using 3,3,3-trifluoropropan-1-amine, to obtain after treatment and purification 2.0 g (81 Fo) of the title compound.

Example 248

M-cyclopropyl-4-16-(2,5-difluorophenyl)sulfanyl)|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y-2-methylbenzamide he he

Fe Fe ve m" / neck 7" / oi r ; re

M M o nn o nn 50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M- cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 2,5-difluorobenzenethiol to give, after work-up and purification, 10.4 mg (17 95) of the title compound. 1H-NMR (0M5O -46): b- 0.49 (2Н), 0.65 (2Н), 1.14 (6Н), 2.20 (ЗН), 2.79 (1Н), 3.25 (2Н), 4, 71 (1), 6.35 (1H), 7.04 (1H), 7.08 (1H), 7.42-7.51 (2H), 7.57 (1H), 7.62 (1H) , 7.66 (1H), 7.94 (1H), 8.22 (1H) ppt.

Example 249

M-cyclopropyl-4-16-((3,4-difluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2 -methylbenzamide

HER

In U

MN MN

DU - DK

Vez y v zy and "I" V» oi and he

50 mg (104 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)y"N-cyclopropyl-2- of methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 3,4-difluorobenzenethiol, to give after work-up and purification 5.0 mg (8 95) of the title compound. 1H-NMR (SOCIZ): b- 0.64 (2H), 0.90 (2H), 2.42 (ZH), 2.52 (2H), 2.93 (1H), 3.61 (2H), 5.88 (1H), 8 .90 (1H), 5.94 (1H), 7.20-7.28 (2H), 7.39 (1H), 7.51 (1H), 7.56 (1H), 7.57 (1H ), 7.70 (1H) ppt.

Example 250

M-cyclopropyl-4-/6-((4-fluorophenyl)sulfanyl|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u.2 -methylbenzamide

HER

In U

МН МН вы зм -ЛО62иЛ0У- и / ой Хон 50 mg (104 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazine- 3-yl)"N-Cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 4-fluorobenzenethiol to give, after work-up and purification, 3.8 mg (7 95) of the title compound. 1H-NMR (SOSIS): b- 0.64 (2H), 0.90 (2H), 2.41 (3H), 2.50 (2H), 2.93 (1H), 3.59 (2H) , 5.87 (1H), 5.88 (1H), 5.96 (1H), 7.15 (2H), 7.19 (1H), 7.55 (1H), 7.59 (1H), 7.64 (2H), 7.70 (IN) ppt.

Example 251

M-cyclopropyl-4-16-((3,5-difluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2 -methylbenzamide

HER

In U

MN MN

DU - TO

In winter, in winter, To r

M M o nn o nn 50 mg (104 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl))"M -cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate Example 247a, was converted analogously to Example 51 using 3,5-difluorobenzenethiol to give, after work-up and purification, 2.9 mg (5 95) of the title compound. 1H-NMR ( SOSIZ): b- 0.63 (2Н), 0.90 (2Н), 2.43 (ЗН), 2.52 (2Н), 2.93 (1Н), 3.62 (2Н), 5.86 (1H), 5.96 (1H), 6.00 (1H), 6.88 (1H), 7.18 (2H), 7.29 (1H), 7.65 (1H), 7.69 ( 1H), 7.73 (1H) ppt.

Example 252

M-cyclopropyl-4-16-(2,3-difluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2- methyl benzamide

HER

In U

MN MN

TO - DK

In winter and in winter J

E r o r

M M o nn o nn mg (104 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)u"M -cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 2,3-difluorobenzenethiol, obtaining after treatment and purification 1.6 mg (C 95) of the title compound.

1H-NMR (SOSIS): b- 0.63 (2H), 0.90 (2H), 2.39 (3H), 2.54 (2H), 2.93 (1H), 3.62 (2H) , 5.85 (1H), 5.97 (1), 6.10 (1), 7.16 (1H), 7.20 (1H), 7.33 (1H), 7.41 (1), 7, 56 (1H), 7.57 (1H), 7.69 (1H) ppt.

Example 253

M-cyclopropyl-4-(6-(4-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl-g-methylbenzamidone one

Fe / Fo

Ve zm / -« -- Go) zm /

M Z M o M i o M 50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)" M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 4-fluorophenol to give, after work-up and purification, 27.5 mg (49 95) of the title compound. 1H-NMR (0M5O -46): 6- 0.47 (2H), 0.63 (2H), 1.16 (6H), 2.13 (ZH), 2.77 (1H), 3.27 (2H), 4, 73 (1H), 6.16 (1H), 6.95 (1H), 7.16 (1H), 7.24-7.34 (4H), 7.64 (1H), 7.73 (1H) , 7.91 (1H), 8.19 (1H) ppt.

Example 254

M-cyclopropyl-4-(6-(3,4-difluorophenoxy)-8-((2-hydroxy-2-methylpropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide he he

Fo Fe ve / om /

M | and M o U i o M 50 mg (109 μmol) 4-/16-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-b|pyridazin-3-yl)"M -cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 3,4-difluorophenol to give, after work-up and purification, 18.1 mg (31 95) of the title compound. 1H-NMR ( 0М5О-46): 6- 0.47 (2Н), 0.64 (2Н), 1.16 (6Н), 2.14 (ЗН), 2.77 (1Н), 3.27 (2Н), 4 .73 (1H), 6.17 (1H), 7.00 (1H), 7.13 (1H), 7.18 (1H), 7.51 (1), 7.56 (1H), 7, 65 (1H), 7.75 (1H), 7.91 (1H), 8.21 (1H) ppt.

Example 255

M-cyclopropyl-4-16-(2,5-difluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2- methyl benzamide

And I

In U

MN MN

DU - DK vm" / v" /

E r u. 50 mg (104 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl- The 2-methylbenzamide obtained according to Intermediate Example 247a was converted analogously to Example 51 using 2,5-difluorobenzenethiol to give, after work-up and purification, 13.3 mg (22 95) of the title compound. 6- 0.62 (2H), 0.90 (2H), 2.39 (ZH), 2.53 (2H), 2.92 (1H), 3.62 (2H), 5.87 (1H) , 5.97 (1H), 6.06 (1H), 7.14-7.23 (ZH), 7.39 (1H), 7.57 (1H), 7.59 (1H), 7.70 (1H) ppt.

Example 256

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(4- isopropoxyphenoxy)imidazo|1,2-b|Ipyridazin-3-yl)y.2-methylbenzamidone one u/Fe ste vm / sv om" 7

M u M o o o

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 4-isopropoxyphenol to give after work-up and purification 13.7 mg (15 95) of the title compound. 1H-NMR (SOCIZ): 6- 0 .60 (2H), 0.87 (2H), 1.36 (6H), 1.44 (6H), 2.30 (ZH), 2.89 (1H), 3.31 (2H), 104, 52 (1H), 5.87 (1H), 5.93 (1H), 6.52 (1H), 6.91 (2H), 7.11 (2H), 7.19 (1H), 7.58 (1H), 7.64 (1H), 7.74 (1H) ppt.

Example 257

M-cyclopropyl-4-[6-(4-isopropoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino]imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide and EI

In U

MN MN

Ve zm / c) with /

M u M o o o y Ot M 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl) )y"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 4-isopropoxyphenol, obtaining after treatment and purification 9.3 mg (10 95) of the title compound. 1H- NMR (SOSIS): b- 0.59 (2Н), 0.88 (2Н), 1.37 (6Н), 2.32 (ЗН), 2.56 (2Н), 2.88 (1Н), 3 .66 (2H), 4.53 (1H), 5.84 (1H), 5.88 (1H), 5.91 (1H), 6.93 (2H), 7.14 (2H), 7, 22 (1H), 7.62 (1H), 7.73 (1H), 7.79 (1H) ppt.

Example 258

M-cyclopropyl-4-16-(-2,3-difluorophenoxy)-8-((3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide

IS

E E

In a

IS

MN

M MN uFfy 7 se with MAY vm -- with MAM om ok and r

M o 100 mg (207 μmol) 4-(6-bromo-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-5|pyridazin-3-yl)u"M-cyclopropyl-2- methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51, using 2,3-difluorophenol, to obtain after treatment and purification 22 mg (19 95) of the title compound.

1H-NMR (SOSIS): 6- 0.60 (2H), 0.88 (2H), 2.29 (ZH), 2.58 (2H), 2.89 (1H), 3.70 (2H) , 5.86 (1H), 5.96 (1H), 6.07 (1H), 7.06-7.17 (ZH), 7.22 (1H), 7.53 (1H), 7.66 (1H), 7.71 (1H) ppt.

Example 259

M-cyclopropyl-4-/6-(2-fluoro-

B-methylphenoxy)-8-I((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)y.2-methylbenzamide and E

In a

IS

MN

MN uFfy / se with MM vm --k x MM om o u

My 100 mg (207 μmol) 4-(6-bromo-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-5|pyridazin-3-yl)y"N-cyclopropyl-2- of methylbenzamide, which was prepared according to Intermediate Example 247a, was converted analogously to Example 51 using 2-fluoro-5-methylphenol to give, after work-up and purification, 23 mg (20 95) of the title compound. 1H-NMR (SOCIZ): b- 0.60 (2H), 0.88 (2H), 2.27 (ZH), 2.35 (ZH), 2.58 (2H), 2.89 (1H), 3.68 (2H), 5 .84 (1Н), 5.95 (1Н), 6.11 (1Н), 7.00-7.16 (ЗН), 7.21 (1Н), 7.55 (1Н), 7.71 (2Н ) ppm

Example 260

M-cyclopropyl-4-(6-(3,4-difluorophenoxy)-8-((3,3,3-trifluoropropyl)amino)imidazo|(1,2-b|Ipyridazin-3-yl)y-2- methyl benzamide

IS

E E

In a

IS

MN

M MN Ufa 7 / Photo

CHY, vm --A z /M-J om o ii o Я 7 и o nn 100 mg (207 μmol) 4-/6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo|( 1,2-b|Ipyridazin-3-yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 3,4-difluorophenol, obtaining after treatment and purification 36 mg (31 95) of the title compound. 1H-NMR (SOSIS): 6- 0.61 (2H), 0.88 (2H), 2.34 (3H), 2.57 (2H), 2.90 ( 1H), 3.68 (2H), 5.86 (1H), 5.687 (1H), 6.04 (1H), 6.99 (1H), 7.11-7.29 (ZH), 7.59 (1H), 7.71 (1H), 7.72 (1H) ppt.

Example 261

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(2-thienylsulfanyl)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamido h What is it?

M MN

/F y, se

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1, 2-b|pyridazin-3-yl)'M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using thiophene-2-thiol, obtaining after treatment and purification 34 mg (41 95 ) of the title compound.

1H-NMR (0M50-a6): 0- 0.50 (2H), 0.65 (2H), 1.12 (6H), 2.26 (ZH), 2.80 (1H), 1.64 ( 2H), 4.70 (1H), 6.21 (1H), 7.01 (1H), 7.17 (1H), 7.23 (1H), 7.47 (1H), 7.71 (1H ), 7.76 (1H), 7.94 (2H), 8.23 (1H) ppt.

Example 262

M-cyclopropyl-4-[6-(3,5-difluorophenoxy)-8-((2-hydroxy-2-methylpropyl)amino imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide and on che yo

M MN

/F / se vem - k- om 4! g r (c) M M o n 200 mg (436 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|midazol|1,2-5|pyridazin-3-yl) "M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 3,5-difluorophenol, obtaining after treatment and purification 34.6 mg (15 95) of the title compound. 1H- NMR (0M5O-46): 6- 0.47 (2H), 0.63 (2H), 1.15 (6H), 2.17 (ZH), 2.77 (1H), 3.27 (2H) , 4.74 (IN), 6.19 (1H), 7.08 (1H), 7.12-7.22 (4H), 7.68 (1H), 7.79 (1H), 7.93 (1H), 8.23 (1H) ppt.

Example 263

M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino1|-6-1((35)-2-oxopyrrolidin-3-yl|oxyhimidazo|1,2-b|Ipyridazin-3-yl )-2-methylbenzamide

M MN p

UV eh

Vg M ---j o B se

Y Ch MN ur:

My 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl-2- methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using (35)-3-hydroxypyrrolidin-2-one to give, after work-up and purification, 3.2 mg (4 95) of the title compound. 1H-NMR ( SOSIZ): 6- 0.64 (2Н), 0.89 (2Н), 1.40 (6Н), 2.20 (1Н), 2.49 (ЗН), 2.80 (1Н), 2.92 (1H), 3.27 (2H), 3.37-3.51 (2H), 4.04 (1H), 5.33 (1H), 5.82 (1H), 6.09 (1H), 6.18 (1H), 6.34 (1H), 7.38 (1H), 7.57 (1H), 7.74 (1H), 7.80 (1H) ppt.

Example 264

M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino!|-6-((b-methylpyridin-3-y)oxy|imidazo|1,2-bipyridazin-3-yl-2- methylbenzamid on on still /Fo

Vez and o zim Y sy o

M M also 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-B|pyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using b-methylpyridin-3-ol to give, after treatment and purification, 24.5 mg (30 95) of the title compound.

1H-NMR (0M5O-46): b- 0.50 (2H), 0.66 (2H), 1.19 (6H), 2.14 (ZH), 2.51 (ZH), 2.80 ( 1H), 3.32 (2H), 4.76 (1H), 6.23 (1H), 7.02 (1H), 7.19 (1H), 7.37 (1H), 7.64 (1H ), 7.68 (1H), 7.73 (1H), 7.94 (1H), 8.22 (1H), 8.43 (1H) ppt.

Example 265

M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino|-6-(pyrimidin-5-yloxy)imidazo|1,2-b|Ipyridazin-3-yl-g-methylbenzamidone one

Fe / Fo

200 mg (436 μmol) of 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|midazol|1,2-5|pyridazin-3-yl) "M-Cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using pyrimidin-5-ol to give, after work-up and purification, 34.6 mg (15 95) of the title compound. 1H-NMR (SOSIZ): 6- 0.64 (2H), 0.89 (2H), 1.48 (6H), 2.30 (ZH), 2.92 (1H), 3.35 (2H), 4, 81 (1H), 5.87 (1H), 6.41 (1H), 6.62 (1H), 7.23 (1H), 7.45 (1H), 7.51 (1H), 7.58 (1H), 8.52 (2H), 9.05 (1H) ppt.

Example 266 4-(6-(z-chlorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazoi|1,2-BI pyridazin-3-yl)y"-M-cyclopropyl-2-methylbenzamide

IS

E E

In a

IS

MN

75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(1, 2-B|Ipyridazin-3-yl)y'N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 3-chlorophenol, obtaining after work-up and purification 13.9 mg (17 95) of the title compound. 1H-NMR (SOSIS): 6- 0.61 (2H), 0.88 (2H), 2.34 (3H), 2.58 (2H), 2.90 (1H) , 3.68 (2H), 5.82 (1H), 5.89 (1H), 5.97 (1H), 7.15 (1H), 7.25 (1H), 7.27 (1H), 7.91 (1H), 7.36 (1H), 7.63 (1H), 7.72 (1H), 7.74 (1H) ppt.

Example 267 4-(6-(4-chlorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazoi|1,2-BI pyridazin-3-yl)y"-M-cyclopropyl-2-methylbenzamide

IS

E E

In a

IS

MN

MN

FI / se with MAY vm --» 5 MM om 0-X o Ya r

M c on 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-B|Ipyridazin-3-yl)"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 247a,

was converted similarly to Example 51, using 4-chlorophenol, obtaining after treatment and purification 12.6 mg (12.6 95) of the title compound. 1H-NMR (SOSIS): b- 0.61 (2H), 0.88 (2H), 2.33 (3H), 2.57 (2H), 2.90 (1H), 3.68 (2H) , 5.83 (1H), 5.89 (1H), 5.96 (1H), 7.19 (2H), 7.25 (1H), 7.40 (2H), 7.58 (1H), 7.72 (1H), 7.73 (IN) ppt.

Example 268

M-cyclopropyl-4-76-(2-fluorophenyl)sulfanyl|-8-((3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide

IS

E E

In a

IS

MN

M MN from Y vm -" from MAY 87 7M (in Y city

M on 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 2-fluorobenzenethiol to give, after work-up and purification, 31.8 mg (39 95) of the title compound. 1H-NMR (SOCIZ): 6- 0 .62 (2H), 0.90 (2H), 2.37 (ZH), 2.51 (2H), 2.92 (1H), 3.60 (2H), 5.83 (1H), 5, 89 (1H), 5.94 (1H), 7.16 (1H), 7.20 (1H), 7.25 (1H), 7.51 (1H), 7.56 (1H), 7.59 (1H), 7.66 (1H), 7.70 (IN) ppt.

Example 269

M-cyclopropyl-4-76-((5-fluoro-2-methylphenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u .2-methylbenzamide

EII E sa z.

IS

MN

M MN with MY vm -» CHI 877 (in I du and r

My 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-B|Ipyridazin-3-yl)u"N-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51, using 5-fluoro-2-methylbenzenethiol, to give, after work-up and purification, 6.1 mg (7 95) of the title compound. : 6- 0.63 (2H), 0.90 (2H), 2.39 (ЗН), 2.40 (ЗН), 2.50 (2Н), 2.92 (1Н), 3.59 (2Н ), 5.86 (1H), 5.89 (1H), 5.93 (1H), 7.10 (1H), 7.19 (1H), 7.91 (1H), 7.38 (1H) , 7.57 (1H), 7.60 (1H), 7.71 (1H) ppt.

Example 270

M-cyclopropyl-4-(6-C2-(hydroxymethyl)phenyl|sulfanyl)-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)-2 -methylbenzamide and E

In a

IS

MN

МН уФя / с з MAI vm -» xx MAM on o 857M (c) i h o nn zo b

75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide , which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using (2-sulfanylphenyl)methanol to give, after work-up and purification, 12.3 mg (15 95) of the title compound. 1H-NMR (SOSIS): b- 0 .63 (2H), 0.90 (2H), 2.34 (ZH), 2.51 (2H), 2.92 (1H), 3.61 (2H), 4.83 (2H), 5, 86 (1H), 5.89 (1H), 5.94 (1H), 7.14 (1H), 7.41 (1H), 7.42 (1H), 7.50 (1H), 7.57 (1H), 7.65 (1H), 7.68 (1H), 7.70 (1H) ppt.

Example 271

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-((3-methoxyphenyl)sulfanilyimidazo|1,2-5|Ipyridazin-3-yl)y-2-methylbenzamide and he doesn't

M MN ss

Fe 4 /Fe

Ve -- in zm

M 07 Frebu Zh s 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M -cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 3-isopropoxybenzenethiol to give, after work-up and purification, 18.5 mg (20 95) of the title compound. 1H-NMR (0M5O- 46): b- 0.48 (2Н), 0.65 (2Н), 1.11 (6Н), 1.18 (6Н), 2.21 (ЗН), 2.78 (1Н), 3.20 (2H), 4.58 (1H), 4.71 (1H), 6.21 (1H), 6.95-7.05 (2H), 7.08-7.16 (ZH), 7.34 (1H), 7.71 (1H), 7.73 (1H), 7.94 (1H), 8.23 (1H) ppt.

Example 272 (85)-M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino|-6-(pyrrolidin-3-ylamino)imidazo|1,2-5|Ipyridazin-3-yl- 2-methylbenzamidon on on y y sy M Tok

Ve M - N

H o U ne c) 50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M- cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate Example 9ba, was converted analogously to Example 51 using (K5)-pyrrolidin-3-amine to give, after work-up and purification, 18 mg (36 95) of the title compound.1H-NMR (0М5О-46): b- 0.50 (2Н), 0.65 (2Н), 1.16 (6Н), 1.86 (1Н), 2.15 (1Н), 2.36 (ЗН), 2.80 (1), 3.21 (2H), 3.28 (1H), 3.45 (1H), 3.53-3.65 (2H), 3.71 (1H), 4.27 ( 1H), 5.68 (1H), 6.36 (1H), 7.31 (1H), 7.78 (1H), 8.07 (1H), 8.10 (1H), 8.26 ( 1H), 8.29 (1H) ppt.

Example 273

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-|(3-isopropylphenyl)sulfanilyimidazo|1,2-5|Ipyridazin-3-yl)y-2-methylbenzamidone ve on che ne

M MN ss

Fe / /Fo

Вг M --і в в вой 9 -

M o i 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1 2-b|pyridazin-3-yl)"M-cyclopropyl-2- of methylbenzamide, which was prepared according to Intermediate Example 9ba, was converted analogously to Example 51 using C3-isopropylbenzenethiol to give, after work-up and purification, 14.0 mg (15 95) of the title compound. 1H-NMR (0M5O-46): b- 0.48 (2H), 0.64 (2H), 1.10 (6H), 1.14 (6H), 2.18 (ZH), 2.78 (1H), 2.88 (1), 3 .18 (2H), 4.71 (1H), 6.18 (1H), 6.98 (1H), 7.08 (1H), 7.34-7.43 (ZH), 7.45 (1H ), 7.64 (1H), 7.71 (1H), 7.94 (1H), 8.22 (1H) ppt.

Example 274

M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-2-yloxy)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide ve on che yo

M MN ss

UV eh

Vg M ---j o v oi z r

75 mg (164 µmol) 4-[6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-B|pyridazin-3-yl)]N-cyclopropyl- 2-Methylbenzamide, which was prepared according to Intermediate Example 9ba, was converted analogously to Example 51 using pyridin-2-ol to give, after work-up and purification, 11.0 mg (14 95) of the title compound. 1H-NMR (0M50-ab ): b- 0.48 (2Н), 0.64 (2Н), 1.14 (6Н), 2.33 (ЗН), 2.79 (1Н), 5.27 (2Н), 4.73 ( 1H), 6.33 (1H), 6.47 (1H), 6.48 (1H), 7.21 (1H), 7.33 (1H), 7.54 (1H), 7.79 (1H ), 7.82 (1H), 7.91 (1H), 8.03 (1H), 8.24 (1H) ppt.

Example 275

M-cyclopropyl-4-/6-I3-(2-hydroxy-2-methylpropoxy)phenoxy)|-8-((2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazine-3- yl)y-2-methylbenzamido on on

Fe /F

50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2 -b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51, using 3-2-methyl-2-(triisopropylsilyl)oxy|propoxy)uphenol, with obtaining after processing and purification 2.3 mg (4 95) of the title compound. 1.15 (6H), 2.14 (ZH), 2.76 (1H), 3.27 (2H), 3.66 (2H), 4.59 (1H), 4.74 (1H), 6.14 (1H), 6.76-6.86 (ZH), 6.97 (1H), 7.16 (1H), 7.91 (1H), 7.70 (1H), 7.79 (1H), 7.92 (1H), 8.21 (1H) ppt.

Example 276

M-cyclopropyl-4-76-((3-fluorophenyl)sulfanyl|-8-(2-hydroxyethyl)amino)imidazo|1,2-b|pyridazin-3-yl)y.2-methylbenzamide

MN MN

/Fe se vm" / vm /

M and M contain 15 mg (174 μmol) of 4-16-bromo-8-(2-hydroxyethyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which obtained according to Intermediate Example 276a, converted analogously to Example 51 using C3-fluorobenzenethiol, yielding after work-up and purification 14.5 mg (17 95) of the title compound. 1H-NMR (0M5O-46): b- 0.48 (2H), 0.65 (2H), 2.20 (ZH), 2.78 (1H), 3.33 (2H), 3.57 (2H), 4.82 (IN), 6.19 ( 1H), 7.12 (1H), 7.33 (1H), 7.38-7.54 (4H), 7.66 (1H), 7.71 (1H), 7.94 (1H), 8 .23 (1H) ppt.

Intermediate Example 27ba 4-16-bromo-8-K(2-hydroxyethyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)"N-cyclopropyl-2-methylbenzamide is not available for M

MN from M

Fo » Ve M

A total of 198 g (5.17 mmol) of 2-(6-bromo-3-iodoimidazo|(1,2-b|Ipyridazin-8-yl)uamino)ethanol obtained according to Intermediate Example 2760 was converted similarly to Intermediate

Example 1a, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, obtaining after treatment and purification 1.27 d ( 51 Fo) of the compound specified in the title.

Intermediate Example 2765 2-(6-bromo-3-iodoimidazo|(1,2-B|pyridazin-8-yl)amino|)ethanol

Ve il MN su. and c 2 in and -f

Ve M

AND

2.50 g (6.21 mmol) of 6,8-dibromo-3-iodoimidazo(1,2-b|Ipyridazine, which was obtained according to

Intermediate Example 9bs was converted similarly to Intermediate Example 16, using 2-aminoethanol, to obtain after treatment and purification 1.99 g (81 95) of the title compound.

Example 277

M-cyclopropyl-4-(6-(3-fluorophenoxy)-8-K(2-hydroxyethyl)amino|imidazo

P,2-Shipyridazin-3-yl)y-2-methylbenzamide in u

MN MN

Ve zm / in c) zm /

M ge. M

Cheeks

15 mg (174 μmol) of 4-16-bromo-8-(2-hydroxyethyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to the Intermediate Example 276a was converted analogously to Example 51, using 3-fluorophenol, to obtain after treatment and purification 17.2 mg (21 95) of the title compound. 1H-NMR (0M5O-46): b- 0.46 (2H), 0.63 (2H), 2.14 (ZH), 2.76 (IN), 3.38 (2H), 3.62 (2H), 4.84 (1H), 6.08 (1H), 7 ,07-7.20 (ZH), 7.24 (1H), 7.41 (1H), 7.48 (1H), 7.66 (1H), 7.76 (1H), 7.92 (1H ), 8.21 (1H) ppt.

Example 278

M-cyclopropyl-2-methyl-4-(6-(2,2,3,3-tetrafluoro-4-hydroxybutoxy)-8-

I(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazine-3-ilybenzamide (A) and

M-cyclopropyl-2-methyl-4-(6-ShCl1E)-2,3,3-trifluoro-4-hydroxybut-1-en-1-yl|oxy)-8-((3,3,3- triftorpropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)benzamide

E sa in vu

E E

MN

M MN MN y, /Fo /Fo

Vg M -- 2 .M Her and 2. Y vom EURO M

N E r i r o M on on on

And in 100 mg (207 μmol) 4-(6-bromo-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-5|pyridazin-3-yl)u"M-cyclopropyl-2- of methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 2,2,3,3-tetrafluorobutane-1,4-diol to give, after work-up and purification, 5.2 mg (4 95) of the title compound A and 5.3 mg (4 95) of the title compound B. 1H-NMR (OM5O-46) of A: b- 0.50 (2H), 0.65 (2H), 2.35 (ZH), 2.65 (2H), 2.80 (1H), 3.56 (2H), 3.91 (2H), 4.91 (2H), 5.97 (1H), 6.00 (1H), 7 .33 (1H), 7.60 (1H), 7.90 (1H), 7.92 (1H), 7.97 (1H), 8.27 (1H) mp 1H-NMR (0M5O-46) ой B: 6b- 0.50 (2Н), 0.66 (2Н), 2.35 (ЗН), 2.66 (2Н), 2.80 (1Н), 3.59 (2Н), 3.66 (2H), 5.92 (1H), 6.14 (1H), 7.33 (1H), 7.70 (1H), 7.84 (1H), 7.89 (1H), 7.97 ( 1H), 8.02 (1H), 8.28 (IN) ppt.

Example 279 methyl ester 2-13-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-B|pyridazin-6b-yl-5 -Fluoro-benzoic acid is not

M MN

UF / de vm ---- zi Y

E (c) (c) i s h g (c) zo b y 600 mg (1.31 mmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|midazo|1,2 -5|pyridazin-3-yl)"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 1, using 14-fluoro-2-(methoxycarbonyl)/phenyl|boronic acid. After treatment, 19 ml of tetrahydrofuran was added to the crude product and the suspension was cooled to 3 °C. 21.8 ml of a freshly obtained solution of diazomethane in diethyl ether was added in portions over 2 hours. The solvent was removed and the residue was purified by chromatography to give 52.7 mg (995) of the title compound. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.65 (2H), 1.17 (6H), 2.36 (ZH), 2.80 (1H), 3.33 ( 2H), 3.47 (ZH), 4.75 (1H), 6.52 (1H), 6.96 (1H), 7.30 (1H), 7.51-7.59 (2H), 7 .78 (1H), 7.92 (1H), 7.97 (1H), 8.04 (IN), 8.23 (1H) ppt.

Example 280

M-cyclopropyl-4-(6-(2-hydroxyphenoxy)-8-(3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide and and

In U

MN MN

/Fo sho Fo obi obi g o"

M M more

A mixture of 28.0 MG (53 μmol) M-cyclopropyl-4-/16-(2-methoxyphenoxy)-8-

I(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-iluya2-methylbenzamide, which was obtained according to Example 223, 44.8 mg of sodium methanethiolate and 350 μl of M,M-dimethylformamide were heated with microwave irradiation for 30 min. at 120 "C. The mixture was poured into water, the pH was adjusted between 7 and 8 by adding ammonium chloride and extracted with a mixture of dichloromethane and methanol. The combined organic phases were dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to give 11.5 mg (40 95) of the title compound 1H-NMR (0M5O-46): 6- 0.47 (2H), 0.63 (2H), 2.09 (3H), 2.68 (2H), 2 .76 (1H), 3.59 (2H), 6.08 (1H), 6.83 (1H), 6.97 (1H), 7.05-7.17 (ZH), 7.55 (1H ), 7.62 (1H), 7.75 (1H), 7.90 (1H), 8.18 (1H), 9.53 (IN) ppt.

Example 281

M-cyclopropyl-4-(6-(3-fluorophenoxy)-8-(tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamide 5 5 t, t,

Fo Fe -- 15 MG (150 μmol) 4-16-bromo-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo)

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 281a was converted analogously to Example 51, using 3-fluorophenol, obtaining after treatment and purification 33.7 mg (40 95) of the title compound. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.66 (2H), 1.32 (2H), 1.78 (1H), 2.04 (2H), 2.17 ( ЗН), 2.59 (4Н), 2.79 (1Н), 3.22 (2Н), 6.09 (1Н), 7.15 (2Н), 7.18 (1Н), 7.27 (1Н ), 7.50 (1H), 7.68 (1H), 7.72 (1H), 7.78 (1H), 7.93 (1H), 8.22 (1H) ppt.

Intermediate Example 281a 4-16-bromo-8-Ktetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide 5 each

MN - with /Fe with. u/Fo Ve M su. - f

Ve M! and 2.22 g (4.90 mmol) of 6-bromo-3-iodo-M-(tetrahydro-2H-thiopyran-4-ylmethyl)imidazo|1,2-b|Ipyridazin-8-amine, which obtained according to Interim Example 2816,

converted similarly to Intermediate Example 1a, using

M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl/benzamide), obtaining after treatment and purification 1.49 g (55 95) of the specified in the compound header.

Intermediate Example 2816 6-bromo-3-iodo-M-(tetrahydro-2H-thiopyran-4-ylmethyl)imidazo|1,2-b|Ipyridazin-8-amine 5

What

DU O- y

FU - f

Ve M! everything

In the amount of 2.31 g (5.75 mmol) of 6,8-dibromo-3-iodoimidazo(1,2-b|Ipyridazine, which was obtained according to

Intermediate Example 9bs was converted similarly to Intermediate Example 16, using 1-(tetrahydro-2H-thiopyran-4-ylumethanamine), with the result that after processing and purification, 2.23 g (81 Fo) of the title compound was obtained.

Example 282

M-cyclopropyl-4-[6-(3-fluoro-5-methylphenoxy)-8-|(tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl) u.2-methylbenzamide 5 5 s, t,

15 MG (150 μmol) 4-16-bromo-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 281a, converted similarly to Example 51, using 3-fluoro-

B-methylphenol, yielding after treatment and purification 14.1 mg (16 95) of the title compound. 1H-NMR (0M5O-ab): b- 0.50 (2H), 0.66 (2H), 1.32 (2H), 1.77 (1H), 2.04 (2H), 2.18 ( ЗН), 2.34 (ЗН), 2.59 (4Н), 2.79 (1Н), 3.22 (2Н), 6.07 (1Н), 6.96 (1Н), 6.97 (1Н ), 7.04 (1H), 7.20 (1H), 7.68-7.74 (2H), 7.680 (1H), 7.93 (1H), 8.23 (1H) ppt.

Example 283

M-cyclopropyl-4-[6-(2-fluorophenoxy)-8-K(tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2- methylbenzamide 5 5 c, t, /F /Fo -- ve" / (o) zm / o oy oy 15 MG (150 μmol) 4-16-bromo-8-((tetrahydro-2H-thiopyran-4-ylmethyl) amino) imidazo|1,2-b|Ipyridazin-3-yl"-M-cyclopropyl-2-methylbenzamide, which was obtained according to

Intermediate Example 281a was converted analogously to Example 51, using 2-fluorophenol, to obtain after processing and purification 26.6 mg (32 95) of the title compound. 1H-NMR (0M50O-ab): b- 0.49 (2H), 0.66 (2H), 1.33 (2H), 1.80 (1H), 2.06 (2H), 2.11 ( ЗН), 2.60 (4Н), 2.78 (1Н), 3.23 (2Н), 6.16 (1Н), 7.13 (1Н), 7.30 (1), 7.37 (1Н ), 7.43 (1H), 7.47 (1H), 7.61 (1H), 7.69 (1H), 7.74 (1H), 7.93 (1H), 8.21 (1H) ppt

Example 284

M-cyclopropyl-2-methyl-4-/6-(phenylsulfanyl)-8-((tetrahydro-2H-thiopyran-4-

ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl)ibenzamid t, t, -- vm , A , on on 15 MG (150 μmol) 4-16-bromo-8-((tetrahydro- 2H-thiopyran-4-ylmethyl)amino|imidazo

P,2-Shipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate 5 Example 281a, was converted analogously to Example 51 using benzenethiol, obtaining after treatment and purification 45.3 mg (54 95) of the title compound. 1H-NMR (0M5O-46): b- 0.48 (2H), 0.65 (2H), 1.22 (2H), 1.60 (1H), 1.91 (2H), 2.21 ( ЗН), 2.52 (4Н), 2.78 (1Н), 3.08 (2Н), 5.99 (1Н), 7.10 (1Н), 7.44-7.53 (ЗН), 7 .59-7.73 (5H), 7.91 (1H), 8.24 (1H) ppt.

Example 285

M-cyclopropyl-4-[6-((3-fluorophenyl)sulfanyl|-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u .2-methylbenzamide 5 5 t, t, /F /Fo --f.

MG (150 μmol) of 4-16-bromo-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo 15P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to the Interim

Example 2814 was converted similarly to Example 51, using 3-fluorobenzenethiol, to obtain after treatment and purification 9.8 mg (11 95) of the title compound. 1H-NMR (0M5O-46): b- 0.49 (2H), 0.65 (2H), 1.23 (2H), 1.64 (1H), 1.93 (2H), 2.21 ( ЗН), 2.53 (4Н), 2.79 (1Н), 3.11 (2Н), 6.10 (1Н), 7.13 (1Н), 7.34 (1Н), 7.44 (1Н ), 7.48-7.54 (2H), 7.68 (1H), 7.72 (1), 7.74 (1H), 7.93 (1H), 8.25 (1H) ppt.

Example 286

M-cyclopropyl-4-(6-|(3-fluoro-5-methylphenyl)sulfanyl)|-8-(tetrahydro-2H-thiopyran-4-ylmethyl)aminoimidazol|1,2-b|pyridazin-3-yl -2-methylbenzamide 5 5 c, t, /F /Fo --» vy vy ry r roy oy 15 MG (150 μmol) 4-(6-bromo-8-((tetrahydro-2H-thiopyran-4-ylmethyl )amino|imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 281a, converted similarly to Example 51, using 3-fluoro-

B-Methylbenzenethiol, with treatment and purification yielding 9.1 mg (10 95) of the title compound. 1H-NMR (0M5O-46): b- 0.48 (2H), 0.65 (2H), 1.23 (2H), 1.62 (1H), 1.92 (2H), 2.21 ( ЗН), 2.31 (ЗН), 2.52 (4Н), 2.79 (1Н), 3.11 (2Н), 6.07 (1Н), 7.14 (1Н), 7.17 (1Н ), 7.26-7.32 (2H), 7.68-7.76 (HN), 7.93 (1H), 8.25 (1H) ppt.

Example 287

M-cyclopropyl-4-16-|(3-hydroxyphenyl)sulfanyl|-8-Ctetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2- methylbenzamide 5 c, t,

Fe /F --» vm" / 5 zm / r ver roy oy 100 mg (200 μmol) 4-(6-bromo-8-Ktetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo 5 P,2- 5-Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 281a, converted similarly to Example 51, using

3-Methoxybenzenethiol, with treatment and purification yielding 14 mg (12 95) of the title compound. 1H-NMR (0M5O-46): b- 0.49 (2H), 0.65 (2H), 1.22 (2H), 1.58 (1H), 1.90 (2H), 2.24 ( ЗН), 2.52 (4Н), 2.79 (1Н), 3.07 (2Н), 5.95 (1Н), 6.686 (1Н), 6.96 (1Н), 7.01 (1Н), 7.17 (1H), 7.26 (1H), 7.69 (1H), 7.73-7.80 (2H), 7.92 (1H), 8.24 (1H), 9.76 ( 1H) ppt.

Example 288

M-cyclopropyl-2-methyl-4-16-(pyridin-3-yloxy)-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl )ibenzamid 5 5 t, t, -»

15 MG (150 μmol) 4-16-bromo-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 281a was converted similarly to Example 51, using pyridin-3-ol to obtain after treatment and purification 25.2 mg (31 95) of the title compound. 1H-NMR (0M5O-ab): b- 0.46 (2H), 0.63 (2H), 1.30 (2H), 1.76 (1H), 2.02 (2H), 2.12 ( ЗН), 2.57 (4Н), 2.76 (1Н), 3.20 (2Н), 6.13 (1Н), 7.13 (1Н), 7.51 (1), 7.60 (1Н ), 7.68 (1H), 7.76 (1H), 7.80 (1H), 7.90 (1H), 8.21 (1H), 8.48 (1H), 8.57 (1H) ppt

Example 289

M-cyclopropyl-4-16-((2-hydroxyphenyl)sulfanyl|-8-Ctetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2- methylbenzamide 5 5 t, no

Pho Fe --»

Ve zm / 5 zm /

Soy 15 mg (150 μmol) 4-16-bromo-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 281a was converted analogously to Example 51, using 0 2-methoxybenzenethiol, to obtain after treatment and purification 40.9 mg (4895) of the title compound.

1H-NMR (0M50O-ab): b- 0.49 (2H), 0.65 (2H), 1.20 (2H), 1.57 (1H), 1.688 (2H), 2.23 (3H) , 2.52 (4H), 2.79 (1H), 3.03 (2H), 5.86 (1H), 6.687 (1H), 6.98 (1H), 7.12 (1H), 7, 34 (1H), 7.46 (1H), 7.60 (1H), 7.72 (1H), 7.74 (1H), 7.90 (1H), 8.23 (1H), 10.01 (1H) ppt.

Example 290

M-cyclopropyl-4-(6-(4-fluorophenoxy)-8-tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamide 5 5 mg (150 μmol) 4-16-bromo-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo

P,2-Shipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 281a was converted analogously to Example 51, using 4-fluorophenol, to obtain after treatment and purification 45.6 mg (54 95) of the title compound. 1H-NMR (0M50-ab): b- 0.46 (2H), 0.63 (2H), 1.29 (2H), 1.75 (1H), 2.02 (2H), 2.12 ( ЗН), 2.56 (4Н), 2.76 (1Н), 3.19 (2Н), 6.06 (1Н), 7.15 (1Н), 7.23-7.35 (4Н), 7 .63 (1H), 7.68 (1H), 7.72 (1H), 7.90 (IN), 8.21 (1H) ppt.

Example 291 4-(6-(4-chloro-3-fluorophenoxy)-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|1,2-b|pyridaz in-3-yl)U- M-cyclopropyl-2-methylbenzamide 5 5 t, t, /F /Fo --хх

Ve zm / c) zm / r zeadoy a on 15 mg (150 μmol) 4-16-bromo-8-(Ctetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 281a was converted analogously to Example 51, using 4-chloro-3-fluorophenol, to obtain after treatment and purification 5.4 mg (6 95) of the title compound. 1H-NMR (SOSIS): b- 0.64 (2H), 0.91 (2H), 1.54 (2H), 1.80 (1H), 2.20 (2H), 2.37 (ЗН) , 2.65-2.79 (4H), 2.93 (1H), 3.26 (2H), 5.86 (1H), 5.67 (1H), 5.97 (1H), 7.04 (1H), 7.16 (1H), 7.30 (1H), 7.46 (1H), 7.62 (1H), 7.74 (2H) ppt.

Example 292 4-(6-(4-chlorophenoxy)-8-(tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo

P,2-Shipyridazin-3-yl)u-M-cyclopropyl-2-methylbenzamide 5 5 t, t, --

Vu i o Z 6) i si 6) i 15 mg (150 μmol) 4-16-bromo-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 281a was converted analogously to Example 51, using 4-chlorophenol, to obtain after treatment and purification 30.7 mg (36 95) of the title compound. 1H-NMR (0M5O-46): b- 0.46 (2H), 0.63 (2H), 1.29 (2H), 1.75 (1H), 2.02 (2H), 2.12 ( ЗН), 2.56 (4Н), 2.77 (1Н), 3.19 (2Н), 6.07 (1Н), 7.16 (1Н), 7.91 (2Н), 7.50 (2Н ), 7.62 (1H), 7.72 (2H), 7.90 (1H), (821 1H) ppt.

Example 293

M-cyclopropyl-4-16-(-2,3-difluorophenoxy)-8-|(tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u. 2-methylbenzamide 5 5 t, t, so s -»

Ve zm / c) zm / ver r E r oy oy

MG (150 μmol) 4-16-bromo-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 281a was converted analogously to Example 51, using 2,3-difluorophenol, obtaining after treatment and purification 19.1 mg (22 95) of the title compound. 1H-NMR (SOSIS): b- 0.60 (2H), 0.88 (2H), 1.52 (2H), 1.79 (1H), 2.19 (2H), 2.30 (3H) , 2.61-2.79 15 (4H), 2.89 (1H), 3.25 (2H), 5.82 (1H), 5.92 (2H), 7.05-7.17 (ЗН ), 7.22 (1H), 7.54 (1H), 7.68 (1H), 7.70 (1H) ppt.

Example 294 4-(6-(4-chlorophenoxy)-8-1(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)umethyl amino)imidazo(1,2-b|Ipyridazin-3-yl|-HM -cyclopropyl-2-methylbenzamide (A) and 4-(6--4-chlorophenoxy)-8-(|(cis/htrans)-1-oxidotetrahydro-2H-thiopyran-4-yl methyl)amino)imidazo|1, 2-5|Ipyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide (B) 5

MN MN MN

/ Fo -- 223 b be om o7tm and ote 7

ZA" with U shchi on si o Ye si o sa

And in

To a solution of 22.4 MG (41 μMOL) 4-(6-(4-chlorophenoxy)-8-(tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|1,2-b|pyridazin-3-yl) "M-cyclopropyl-2-methylbenzamide, which was obtained according to Example 292 in 327 μl of trichloromethane, was added 13.7 mg of 3-chlorobenzenecarboperoxoic acid (77 95), and the mixture was stirred at 23 "C for 40 minutes. Saturated sodium bicarbonate solution was added and the solvents were removed. The residue was purified by chromatography to give 9.1 mg (38 95) of the title compound A and 3.1 mg (13 95) of the cis/trans mixture of the title compound B. 1H-NMR (0M50-a6) and A: 6b - 0.47 (2H), 0.63 (2H), 1.66 (2H), 1.98-2.15 (ZH), 2.12 (ZH), 2.77 (1), 2.97 -3.15 (4H), 3.25 (2H), 6.16 (1H), 7.17 (1H), 7.30 (2H), 7.50 (2H), 7.62 (1H), 7.72 (1H), 7.79 (1H), 7.91 (1H), 8.19 (1H) ppt. 1H-NMR (0M50-a6) and B: b- 0.46 (2H), 0.63 (2H), 1.65 (2H), 1.95-2.17 (ZH), 2.12 (ZH ), 2.76 (1), 2.96-3.16 (4H), 5.27 (2H), 6.17 (1H), 7.16 (1H), 7.30 (2H), 7, 50 (2H), 7.62 (1H), 7.72 (1H), 7.82 (1H), 7.91 (1H), 8.22 (1H) ppt.

Example 295

M-cyclopropyl-4-I8-4(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)umethylamino)-6-(4-fluorophenoxy)imidazo|1,2-b|Ipyridazin-3-yl|-2 -methylbenzamide (A) and M-cyclopropyl-4-(6-(4-fluorophenoxy)-8-H|(cis/trans)-1-oxidotetrahydro-2H-thiopyran-4-ylmethyl)amino)imidazo|1,2 -5|Ipyridazin-3-yl|-2-methylbenzamide (B)

o o chn MN x, /Fi y - Fo b be

Z M o z o z Y yav od" ol

M

E o nn E o M E o M

And in 37 mg (70 μmol)

M-cyclopropyl-4-[6-(4-fluorophenoxy)-8-(tetrahydro-2H-thiopyran-4-ylmethyl)aminoimidazo|1,2-Bb|pyridazin-3-yl)-2-methylbenzamide, which was obtained according to Example 290, was converted similarly to Example 294, obtaining after processing and purification 5.2 mg (13 95) of the title compound A and 1.7 mg (4 95) of the cis/trans mixture of the title compound B. 1H - NMR (0M50-a6) of A: 6b- 0.47 (2Н), 0.63 (2Н), 1.66 (2Н), 1.95-2.17 (ЗН), 2.12 (ЗН) , 2.76 (1), 2.97-3.16 (4H), 3.22 (2H), 6.15 (1H), 7.15 (1H), 7.23-7.36 (4H) , 7.63 (1H), 7.72 (1H), 7.76 (1H), 7.90 (1H), 8.19 (1H) ppt. 1H-NMR (0M50-a6) and B: b- 0.47 (2H), 0.63 (2H), 1.38 (1H), 1.64-2.26 (5H), 2.12 (ЗН ), 2.57 (2H), 2.67-2.88 (2H), 3.19 (2H), 6.11 (1H), 7.15 (1H), 7.22-7.35 (4H ), 7.63 (1H), 7.68-7.77 (2H), 7.90 (1H), 8.19 (1H) ppt.

Example 296

M-cyclopropyl-4-I8-4(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)umethylamino)-b-(pyridin-3-yloxy)imidazo(1,2-b|Ipyridazin-3-yl| -2-methylbenzamide (A) and M-cyclopropyl-2-methyl-4-18-(|(cis)-1-oxidotetrahydro-2H-thiopyran-4-yl methyl)amino)-6-(pyridin-3-yloxy) )imidazo|1,2-b|pyridazin-3-yl|benzamide (B) and M-cyclopropyl-2-methyl-4-I8-"trans)-1-oxidotetrahydro-2H-thiopyran-4-yl methyl)amino )-6-(pyridin-3-yloxy)imidazo|1,2-b|pyridazin-3-yl|benzamide (C) about 5

Go , , s, cha M -- -- ss. i Dn i se s

І и 24 4 s и о и и ? ?7 M r M r o n o nn on on

A in c 171 mg (33 μmol)

M-cyclopropyl-2-methyl-4-16-(pyridin-3-yloxy)-8-tetrahydro-2H-thiopyran-4-ylmethyl)aminoimidase 911,2-5|Ipyridazin-3-yl)benzamide, which was obtained according to with Example 288, was converted similarly to Example 294, obtaining after treatment and purification 6.7 mg (37 905) of the title compound A, 2.4 mg (12 Fo) of the title compound B and 3.1 mg (16 95 ) of the compound indicated in the title C. 1H-NMR (SOSIS) of A: b- 0.61 (2H), 0.88 (2H), 1.96-2.11 (3H), 2.29 (2H), 2.32 (ZH), 2.89 (1H), 3.04 (2H), 3.14 (2H), 3.37 (2H), 5.90 (1H), 5.92 (1H), 6 .51 (1H), 7.24 (1H), 7.40 (1H), 7.55 (1H), 7.62 (1H), 7.64 (1H), 7.72 (1H), 8, 54 (1H), 8.61 (1H) ppt. 1H-NMR (SOSIS) of B: b- 0.61 (2H), 0.88 (2H), 1.87-2.01 (ZH), 2.24 (2H), 2.32 (ZH), 2.48 (2H), 2.89 (1H), 3.10 (2H), 3.33 (2H), 5.89 (1H), 5.92 (1H), 6.02 (1H), 7 .24 (1H), 7.39 (1H), 7.56 (1H), 7.62 (1H), 7.66 (1H), 7.71 (1H), 8.53 (1H), 8 .60 (1H) ppt. 1H-NMR (SOSIS) of C: b- 0.61 (2H), 0.688 (2H), 1.57 (2H), 1.99 (1H), 2.29 (2H), 2.31 (3H) , 2.68 (2H), 2.89 (1H), 3.30 (2H), 3.40 (2H), 5.87-5.92 (2H), 5.99 (1H), 7.23 (1H), 7.39 (1H), 7.55 (1H), 7.62 (1H), 7.65 (1H), 7.71 (1H), 8.53 (1H), 8.60 (1H) ppt.

Example 297

M-cyclopropyl-4-I8-4(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)umethyliamino)-

6-(2-fluorophenoxy)imidazo|(1,2-b|Ipyridazin-3-yl|-2-methylbenzamide

MN in

KU - sr zem MY o m o m o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

M-cyclopropyl-4-(6-(2-fluorophenoxy)-8-(tetrahydro-2H-thiopyran-4-ylmethyl)aminoimidazo|1,2-Bb|pyridazin-3-yl)-2-methylbenzamide, which was obtained according to Example 283, was converted similarly to Example 294, obtaining after treatment and purification 9.8 mg (47 95) of the title compound. 1H-NMR (SOSIS): b- 0.60 (2H), 0.88 (2H), 1.94-2.08 (ZH), 2.26 (ZH), 2.28 (2H), 2, 89 (1H), 3.02 (2H), 3.13 (2H), 3.36 (2H), 5.82 (1H), 5.94 (1H), 5.99 (1H), 7.17 -7.33 (5H), 7.53 (1H), 7.68 (1H), 7.71 (IN) ppt.

Example 298

M-cyclopropyl-4-I8-4(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)umethylamino)-6-(3-fluorophenoxy)imidazo|(1,2-b|Ipyridazin-3-yl|- 2-methylbenzamide (A) and M-cyclopropyl-4-(6-(3-fluorophenoxy)-8-(|(cis/trans)-1-oxidotetrahydro-2H-thiopyran-4-ylmethyl)amino)imidazo|1, 2-5|Ipyridazin-3-yl|-2-methylbenzamide (B) 5 oo o chn MH MH s M se - de DV o M ol o zm

E hurrah C u: C u:

M M M on o n o n

And in 25.5 mg (48 μmol)

M-cyclopropyl-4-(6-(3-fluorophenoxy)-8-(tetrahydro-2H-thiopyran-4-ylmethyl)aminoimidazo|1,2-Bb|pyridazin-3-yl)-2-methylbenzamide, which was obtained in accordance with Example 281, was converted similarly to Example 294, obtaining after treatment and purification 12.3 mg (43 95) of the title compound A and 5.6 mg (21 95) of a cis/trans mixture of the title compounds B. 1H- NMR (SOSIS) for A: 6b- 0.61 (2Н), 0.88 (2Н), 1.93-2.08 (ЗН), 2.28 (2Н), 2.33 (ЗН), 2, 89 (1H), 3.02 (2H), 3.13 (2H), 3.35 (2H), 5.84 (1H), 5.86 (1H), 6.04 (1H), 6.95 -7.09 (ЗН), 7.25 (1Н), 7.39 (1Н), 7.81 (1Н), 7.72 (1Н), 7.74 (1Н) ppt. 1H-NMR (SOSIS) for B: 6b- 0.60 (2H), 0.88 (2H), 1.55 (1H), 1.89 (1H), 1.97 (1H), 2.15- 2.31 (2H), 2.32 (ZH), 2.47--2.67 (2H), 2.89 (1H), 3.08--3.39 (2H), 3.29 (2H ), 5.84--5.87 (1Н), 5.89 (1Н), 6.13 (1Н), 6.95-7.07 (ЗН), 7.25 (1Н), 7.39 ( 1H), 7.61 (1H), 7.72 (1H), 7.74 (1H) ppt.

Example 299

M-cyclopropyl-4-76-(4-fluoro-2-(hydroxymethyl)phenyl|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y- 2-methylbenzamidon on on u/Fo Dn vm / Ch-0-k zm /

E on h t? o nn o nn

250 mg (545 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|midazol|1,2-5|pyridazin-3-yl)y"N-cyclopropyl-2-methylbenzamide , which was obtained according to Intermediate Example 9ba, was converted analogously to Example 1, using 14-fluoro-2-(hydroxymethyl)phenyl|Iboronic acid, which was obtained according to Intermediate Example 299a, obtaining after treatment and purification 239 mg (87 95) of the indicated in the title compound. 1H-NMR (OM50O-ab): b- 0.48 (2H), 0.64 (2H), 1.15 (6H), 2.34 (3H), 2.79 (1H), 3.28 (2H), 4.65 (2H), 4.73 (1H), 5.91 (1H), 6.41 (1H), 6.97 (1H), 7.19 (1H), 7 .32 (1H), 7.40 (1H), 7.53 (1H), 7.91 (1H), 7.95 (1H), 7.99 (1H), 8.26 (1H) ppt.

Intermediate Example 299a

I4-fluoro-2-(hydroxymethyl)phenyl|boronic acid on on

Von Von -» dk dk

OTIRB on

To a solution of 2.60 g (7.97 mmol) of (4-fluoro-2-triisopropylsilyl)oxy|methylphenyl)boronic acid, which was obtained according to Intermediate Example 299p, in 10 ml of dichloromethane was added 6b, 14 ml of trifluoroacetic acid, and the mixture was stirred for 16 hours at 23 "7C.

The solvent was removed and the residue was crystallized from n-hexane to give 682 mg (50 95) of the title compound.

Intermediate Example 2996 (4-fluoro-2-triisopropylsilyl)oxy|methylphenyl)boronic acid

What

Kon!

Zh. 6520 Zhzh.

OTIRZ OTIR5

7.31 ml of n-butyllithium (2.5M in hexane) at -78 °C. After 20 min of stirring, 5.58 ml of trimethyl borate was added and stirring was continued for another 60 min. The mixture was heated to 23 °C, poured into a saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to give 3.16 g (58 95) of the title compound.

Intermediate Example 299 p

K2-bromo-5-fluorobenzyl)oxy|(triisopropyl)silane

Vg Vg sewed 10) he OTIRZ

To a solution of 5.00 g (244 mmol) (2-bromo-5-fluorophenylmethanol in 100 ml M,

M-dimethylformamide was added to 2.49 g of imidazole, 6.20 ml of chloro(triisopropyl)silane, 1.49 g of M,

of M-dimethylpyridin-4-amine, and the mixture was stirred at 23 "C for 2 days. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to give 8.17 g (93 95) of the compound specified in the title.

Example 300

M-cyclopropyl-4-16-((3,4-difluorophenyl)sulfanyl)|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y-2- methylbenzamide on on

Fo Fe vm / vm /

M o, M (c) (c) zo b b 200 mg (436 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|midazo|1,2-5|pyridazine- 3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba,

was converted similarly to Example 51, using 3,4-difluorobenzenethiol, to obtain after treatment and purification 5.8 mg (2 95) of the title compound. 1H-NMR (SOS3/CO300): b- 0.62 (2H), 0.88 (2H), 1.33 (6H), 2.37 (ZH), 2.89 (1H), 3.22 ( 2H), 5.95 (1H), 6.13 (1H), 6.42 (1H), 7.17 (1H), 7.21 (1H), 7.35 (1H), 7.47 (1H ), 7.51 (1H), 7.52 (1H), 7.62 (IN) ppt.

Example 301

M-cyclopropyl-4-(8-1(1,1-dioxidotetrahydro-2H-thiopyran-4-ylmethylyl|amino)- 6-(3-fluorophenyl)sulfanilyimidazo(1,2-b|pyridazin-3-yl)- 2-methylbenzamide o Ko) 5 o

MH MH vm / vm" / r dron o Y 25 MG (47 μmol) 4-(6-bromo-8-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methyl amino)imidazo(1, 2-b|Ipyridazin-3-yl)y-N-cyclopropyl-2-methylbenzamide, which was obtained according to

Intermediate Example C01a, converted similarly to Example 51, using

C-Fluorobenzenethiol, yielding after work-up and purification 13.0 mg (48 95) of the title compound. 1H-NMR (0M5O-46): b- 0.48 (2H), 0.65 (2H), 1.62 (2H), 1.94 (1H), 2.01 (2H), 2.20 ( ЗН), 2.79 (1), 2.96-3.11 (4Н), 3.23 (2Н), 6.25 (1Н), 7.11 (1Н), 7.34 (1Н), 7 ,44 (1H), 7.49 (1H), 7.54 (1H), 7.65 (1H), 7.70 (1H), 7.82 (1H), 7.94 (1H), 8, 24 (1H) ppt.

Intermediate Example C01a 4-(6-bromo-8-(1,1-dioxidotetrahydro-2H-thiopyran-4-ylylmethyl|amino)imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide (A) and 4-(6-bromo-8-(((cis/htrans)-1-oxidotetrahydro-2H-thiopyran-4-yl) |methyl)amino)imidazo

P,2-5-Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide (B) (c) (c) o o

MN MN h,

M dtu ru Ko

Ve M Ve zim Ve zm sa uhr o n o n o Y

And in 328 MG (655 μMOL) 4-(6-bromo-8-Ktetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)u"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 281a, was converted similarly to Example 294, obtaining after treatment and purification 167 mg (48 95) of the title compound A and 128 mg (38 95) of the title compound B.

Example 302

M-cyclopropyl-4-I8-4(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)umethyliamino)-6-(phenylsulfanyl)imidazo(1,2-B|Ipyridazin-3-yl|---methylbenzamide oo oo and E

25 mg (47 μmol) 4-(6-bromo-8-((1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methylamino)imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 301a was converted analogously to Example 51, using benzenethiol, to obtain after treatment and purification 10.1 mg (26 95) of the title compound. 1H-NMR (0M5O-46): b- 0.48 (2H), 0.65 (2H), 1.61 (2H), 1.91 (IN), 1.99 (2H), 2.19 ( ЗН), 2.78 (IN), 2.96-3.12 (4Н), 3.20 (2Н), 6.15 (1Н), 7.08 (1Н), 7.44-7.53 ( ЗН), 7.58-7.65 (ЗН), 7.69 (1Н), 7.77 (1Н), 7.93 (1Н), 8.23 (1Н) ppt.

Example 303

M-cyclopropyl-2-methyl-4-I8-((cis)-1-oxidotetrahydro-2H-thiopyran-4-yl methyl)amino)-6-(phenylsulfanyl)imidazo|1,2-b|Ipyridazine-3- yl|benzamide (A) and M-cyclopropyl-2-methyl-4-N8-"trans)-1-oxidotetrahydro-2H-thiopyran-4-yl methyl)amino)-6-(phenylsulfanyl)imidazo|1,2- b|Ipyridazin-3-yl|benzamide (B)

And "I Ob" OV he he he

And in 25 mg (48 μmol) 4-(6-bromo-8-«((cis/htrans)-1-oxidotetrahydro-2H-thiopyran-4-yl|methyl)amino)imidazo(1,2-b|Ipyridazine -3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to

Intermediate Example 301a was converted analogously to Example 51 using benzenethiol, obtaining after treatment and purification 3.7 mg (14 95) of the title compound A and 2.5 mg (9 95) of the title compound B. 1H-NMR ( SOSIZ) oi A: 6- 0.62 (2H), 0.89 (2H), 1.75-1.88 (ZH), 2.15 (2H), 2.38 (ZH), 2.42 ( 2H), 2.91 (1H), 3.05 (2H), 3.19 (2H), 5.87 (1H), 5.89 (1H), 5.97 (1H), 7.20 (1H ), 7.41-7.50 (ZH), 7.61-7.686 (4H), 7.69 (1H) ppt. 1H-NMR (SOSIS) of B: 6- 0.62 (2H), 0.89 (2H), 1.46 (2H), 1.83 (1H), 2.17 (2H), 2.39 ( ЗН), 2.60 (2Н), 2.92 (1Н), 3.15 (2Н), 3.34 (2Н), 5.82 (1Н), 5.85 (1Н), 5.90 (1Н ), 7.21 (1H), 7.42-7.51 (HN), 7.61-7.68 (4H), 7.70 (1H) ppt.

Example 304

M-cyclopropyl-4-(6-((3-fluorophenyl)sulfanyl|-8-3 (cis)-1-oxidotetrahydro-2H-thiopyran-4-ylmethyl)amino)imidazo|1,2-5|pyridazine- 3-yl)-2-methylbenzamide (A) and

M-cyclopropyl-4-(6-((3-fluorophenyl)sulfanyl|-8-4 (trans)-1-oxidotetrahydro-2H-thiopyran-4-yl|methyl)amino)imidazo|1,2-B| Ipyridazin-3-yl)-2-methylbenzamide (B)

t 9, 9, x t t

МН МН МН and: Mon: Sh; vy vy vyt g Y r y re o n on on

And in 25 mg (48 μmol) 4-(6-bromo-8-«((cis/htrans)-1-oxidotetrahydro-2H-thiopyran-4-yl|methyl)amino)imidazo(1,2-b|Ipyridazine -3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to

Intermediate Example 301a was converted similarly to Example 81, using 3-fluorobenzenethiol, with the result that after processing and purification, 7.4 mg (27 95) of the title compound A and 4.8 mg (18 95) of the title compound B were obtained. 1H- NMR (SOSIS) of A: 6- 0.63 (2H), 0.89 (2H), 1.74-1.89 (ZH), 2.17 (2H), 2.40 (ZH), 2, 43 (2H), 2.92 (1H), 3.06 (2H), 3.22 (2H), 5.90 (1H), 5.92 (1H), 5.98 (1H), 7.15 (1H), 7.23 (1H), 7.35-7.44 (H), 7.63 (1H), 7.65 (1H), 7.69 (1H) ppt. 1H-NMR (SOSIS) of B: 6- 0.62 (2H), 0.90 (2H), 1.49 (2H), 0.87 (1H), 2.20 (2H), 2.40 ( ЗН), 2.62 (2Н), 2.92 (1Н), 3.19 (2Н), 3.35 (2Н), 5.87 (2Н), 5.93 (1Н), 7.15 (1Н ), 7.24 (1H), 7.35-7.44 (ZH), 7.64 (1H), 7.65 (1H), 7.70 (1H) ppt.

Example 305

M-cyclopropyl-4-76-((4-fluorophenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamidone он с шх ве / п-"5ЙОк ним" /

I I OA he y o y

A mixture containing 75 mg (164 μmol) of 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)y"-M- cyclopropyl-2-methylbenzamide, which was obtained according to

Intermediate Example 9ba, with ml of dimethyl sulfoxide, 61.1 mg of 1,1"-binaphthalene-2,2'-diylbisidiphenylphosphine), 30.0 mg of tris(dibenzylideneacetone)dipalladium (0) and 55 mg of sodium 2-methylpropane-2- olate was heated to 160 "C under microwave irradiation for an hour. The reaction mixture was poured into water and extracted with dichloromethane. The combined organic phases were dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to give 11.3 mg (1495) of the title compound. 1H-NMR (0M5O-46): 6- 0.52 (2H), 0.66 (2H), 1.18 (6H), 2.37 (ZH), 2.81 (1H), 3.15 ( 2H), 4.81 (1H), 5.85 (1H), 6.55 (1H), 7.10 (2H), 7.35 (1H), 7.65 (2H), 7.76 (1H ), 7.84 (1H), 8.04 (1H), 8.29 (1H), 8.94 (1H) ppt.

Example 306 4-(6-anilino-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2-methylbenzamidone one

Fo Fo viti --onmyi and in Ov oi oi

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using aniline to give, after work-up and purification, 15.8 mg (21 95) of the title compound. 1H-NMR (0M5O-ab): b- 0.51 ( 2H), 0.66 (2H), 1.18 (6H), 2.38 (ZH), 2.81 (1H), 3.16 (2H), 4.81 (1), 5.89 (1H ), 6.53 (1H), 6.90 (1H), 7.27 (2H), 7.34 (1H), 7.66 (2H), 7.77 (1H), 7.85 (1H) , 8.12 (1H), 8.30 (1H), 8.92 (1H) ppt.

Example 307

M-cyclopropyl-4-/6-((3,4-difluorophenyl)amino|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u .2-methylbenzamide on on

Fo Fe

50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazine -3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 3,4-difluoroaniline, obtaining after treatment and purification 8.3 mg (14 95) of the indicated in 1H-NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 1.18 (6H), 2.36 (3H), 2.81 (1H), 3 ,16 (2H), 4.80 (1), 5.85 (1H), 6.65 (1H), 7.22 (1H), 7.91 (1H), 7.34 (1H), 7, 76 (1H), 7.82 (1H), 7.91 (1H), 8.00 (1H), 8.30 (1H), 9.17 (1H) ppt.

Example 308

M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino|-6-(3-methylphenyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamide 50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b| pyridazin-3-yl)'M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using m-toluidine to give after treatment and purification 8.3 mg (16 95) of the title compound . (1H), 3.15 (2H), 4.81 (1H), 5.89 (1H), 6.51 (1H), 6.71 (1H), 7.14 (1H), 7.33 ( 1H), 7.40 (1H), 7.51 (1H), 7.77 (1H), 7.95 (1H), 8.01 (1H), 8.29 (1H), 8.83 (1H ) ppm

Example 309

M-cyclopropyl-4-76-((5-fluoro-2-methylphenyl)amino|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|pyridazin-3-yl)u -2-methylbenzamide is on it

Fo / F

50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazine-3 - yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba,

was converted similarly to Example 305, using 5-fluoro-2-methylaniline, to obtain after treatment and purification 5.9 mg (11 95) of the title compound. 1H-NMR (0M5O-46): b- 0.49 (2H), 0.64 (2H), 1.19 (6H), 2.23 (ZH), 2.26 (ZH), 2.79 ( 1H), 3.17 (2H), 4.82 (1H), 6.15 (1H), 6.51 (1H), 6.74 (1H), 7.18 (1H), 7.23 (1H ), 7.77-7.687 (ZN), 7.95 (1H), 8.01 (IN), 8.25 (1H) ppt.

Example 310

A-16-(4-chlorophenyl)amino|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|!1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2-methylbenzamidone en ) vimy 4 to 4 on a on 50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)u "M-Cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 4-chloroaniline, obtaining after treatment and purification 8.1 mg (15 95) of the title compound. 1H-NMR (0M5O-46): 6- 0.52 (2H), 0.67 (2H), 1.18 (6H), 2.38 (ZH), 2.81 (1H), 3.16 ( 2H), 4.80 (1), 5.67 (1H), 6.60 (1H), 7.29 (2H), 7.37 (1H), 7.67 (2H), 7.77 (1H ), 7.84 (1H), 8.02 (1H), 8.30 (1H), 9.08 (1H) ppt.

The following examples of compounds were prepared analogously to the procedure described in Example 51, using the appropriate intermediate and the corresponding alcohols, thiols, or amines.

LC-MS Method A, unless otherwise specified) |: practice Structure; Name | Analytical data inn AK cont kpk uyu EK AAU KAAAKN KANTA AAU KA AAU A AAAATN KA AAU VAAAAAA MK AAAAnKya nen po a zy | m M-diclopropyl-ya-8-3rto | 1H!-YMe (MBO ex y | rphenoxy)-8-(C1-methylait |o47 en); 083 (2), 133)

A, | eridinevilylmethyliaminoi | (233, 1.77 (3H), Z, 1x (ZN),

It is: ry tnek, and yVO; and midazoi 1,2-piperidazine-3-th | 237 (2) A (Z) in, | pi2-methylbenzamide | (1), 3.05 (28); 3.23 (2),

Ж m | and wait for me a a What is the meaning of the dream?

Shelter. Stukura 00000 | Knife 00000000 Analytical data 0000 lower (183, 7.78 IN), 791 (B). orto Tue:

529.65 times the number of NN and svia m was detected or | Kecyclopropyl-i(B-PZch(dy | INYAMR (OMVO et

G | methypamino)propyl|amino) 0.47 (2H), 0.62 (2H), 1.85

B F | "in (Zafluorophenoxy midase | (2) Y etipbenzamid den) 807 (IN), 708 shchi one | | tivnu TA? YN) 728. i» | In), tav in) 766 (IN), (tlv nu, tia IN), tv (IN) rot (ntebz

Mu was found out of 5036

MUM calculated "509.6 and nolotons of its tue 0000 sh | rfenoxim8-C2(methipsu | MU found: 52468 with seh | pfonip)ethylaminomide | MUU calculated "523.8 o tati | 3o11,2-BIpyridazine-Z-ily-I-

KI methylenzamide : I- ! | ! 4 | you | AB (o-amino-e-methygyro | 1nNAYAMe (MBO

Well, | pilamino 6-(3-fluoropheno (at (gin), 6.63 (2H), 125.

GREED | xyimidazoi1.2-vipyridases vn) 2.14 (ZNO), 2.78 (IN), on Y n-z- (350 (an) 631 НУ 7. v | ip M-cycloprovyl-2-methy | (FI) , 7.17 183, 7.24 PN), ! to them lbenzamid became nu tv Nu t (tn), tv mon), v2ya (IN), ! 8.38.

MUU was detected - 489.6

MU is calculated by haVEV. 60000000 Caetidisimethy WTO 00000

Co | vminoi b-fenoxyimidazoii | MAMA was detected x 469.8 sv F | "2-Yupyridazine-3- | MU calculated -468.6 sh | tA Mecyclopropyl-e-methy c | pbenzamide she a she she

With ok | Mapyclopropiachi-(8-(2-id | LN-NMR (MBO) ich | roxy-2-methylpropyluamine | 09 (28). 0.852), 1 pd shSChy; | ogachan- 24-triazolZil (BN), 228 (ZN) . (2H), 7.88 (28), 7.95

WELL; 827 NU 882 (B) more | in Tue" b8B

MU? found "785.6 1817 What / Mediclopropyl-448-Co-id | Tuesday - 0! t | roxy-2-methylpropyl)amine | MUU was detected x 492.6 id g 7 | o1-5-(4-methyl-1H-midazole | FLY calculated 54915 nka a in Kvas py nya and

Kk E | "2chil) sulfanihimidazogi, se p 2-v|niridazinoZ-v y | ipiolmethyloenzamide and | Mecyclopropyl-Y(8-(eyes | LN-NMR (OMVO i | roxy-2-methylpropytsamine | 0.50 (2), 0565 (2), pe Ko; | ov Numidazole-ochlsul | (НУ 2.59 (3Н ), 5 (1, sh- shi / phanyl)imidazo!,2-c)pyride | 3.19 (2H), 6.13 (1H), 7.00 y re: | zineZti i-methypbenzamide | (Nu 7201 ), 7691),

NK | | 774 1), 784 IN), VO (en) 824 (Nu rot

And lnninoi mya 00000000 pi, OO oto xPrykya. ; Structure Name | Analytical data and nin nn in p o rn i: | | MU" was found x 478.5; | | Go. and | | MU is calculated x477.6 818 VN | Mecyclopropyp-ya-(8-Co-tide | KT 087 ! I | roxy-2-methylpropyluamine | MUU vyanpeno g 476.5 ! Ak | : : ! ! ! rot | vI-b-((-methyl-yH-pyrazole - | MUM is calculated for 786 baked goods. You

Y r | Bl)oxyimidazoi!,2-B)pyr. her X : H | AND! and and" | idazine-z-

N y y y Y N : m | It-2-methypoOenzamide (320 «one | M-cyclopropyl-4-48-(2-hyd) CT: 0.81 ! | And more !!

Yi tsik, more | Roxymethylpropylamine / MUU was detected - 556.7 su, СбоО | o1-6-14-(riregakhin-1-ipufen MM calculated "Bob?

SHY X | oxy|imidazo 1,2-B1pridase: ! ! | i and j i i i In-Z-it 2:methylbenzamide o write in Vol a

For | san | mcyclopropyl-y-(b-(2-id | 1H-NMR (0MVOchavu ho ! | pa | roxy-2-methyllrogytsamine | 055 (2 0.782 130

N N M : A I va be | Oyechyl-methyln-pyrazole" ((bH). 228 (30), 2.82 shOH nn | acyloxymidazoli!,2-Bipyr 3.19 (2), 3.75 (ZH), 573

EOorlioidazine-Z- | IN). bzbvIyN), 878 (IN), and zn ili-?-methypbenzamide OTYia (2), 7.33 2), 74 and and ! at. | ! shchi (en), 7,581), 8:08 (1H) shk | (vet

Vte0ov and | | MUU was detected x 478.8

AI and | | MU calculated watt 322 t -E tri-butyl | KG t 1.36

Bi | 4-43 hcyclopropylka | MU was detected - 566.8

St | rebamaili-z-methyleniya B | MU Considered "BV. and and zi 'y;

In SU | "Kolydroxy-ia-methyprogi or shi | p)aminoimidazog1,2-bipyrs

Du piaminoimidazop I fIPiri : : - oi ' and zle vih a | inroxyphenylinicherazine - | Ezharbosylat!

Prieyi Strupura; shi S SYN

ЗЗ | (with ! Mm-cyclopropyl-a-15-(3-ft | TYM MBO aVI os v | orphenoxy)-8-(tetrahydro / 0.46 (24), 0.64 (2), 121.)

A A av | "-VNiran-dchilmethyltamino | (ZNU in) 1931), aaoy | Yamidazog! 2-Bitridazine-z- 214 (ZI 2575 YN 323 r; | ile-methylbenzamide, | (2 327 (OH), Z (NI,

Ka | | 609 (NU oi in, (ZNU 7.25 (IN), TAT IN. 7.85 (1), 7.73 AN), 778 opNu te in), in (mon) shi | orrt Tue 1.30

MUM detected: 516.9 she | |M'M calculated BI5o 00000000 Myclopropyl-iecaft |1H-NMR. (fFMeOchavy se , that | orphenylaminoi-8-(3.3;3-t | omanu, ov (2H), 2:35 with | riftorlpropip)amino|mida | (ZNO); 2.67 (2). 2.80 118), ! Shk nyanno Y zori, 2-ripyridazine-Z- (Zm ZaB(2H) 582 (Nu i; | ip.?-methypbenzamide | 870 NU 721 - 740 i | | (AN), 7.72 (18). 7.78 ( IN), and (782 IN). 805 (IN), 830. anu ag Nu rrt she | | vtetza

MUU detected x 5135:

MUU calculated 512.5 va 16u00000000000000 | Metseclopropitavch3ft | HN-NMR (SOCI3U «5 050. , also | orphenoxy)-in Kz-hydroxy sn 087 (2H), 135 (BN), 2 Kha | -3-methylbutylaminoimide | 1.84 (2H), 2.31 (ZNU, 2.88.

Her oil | zo/1,2-B|pyridazine-3-In), 550 (2n), 588 CH),

With | ilr2-methylbenzamide -bla(n), weight -7.09(ZH), weight (weight NU 738 (NU 760.

b. I anu 770 (2H) rriy te 1.25

МХХ was detected x 5046 nsh NN sia

Application | Structure (pava | C lnalytical data from | in | 446-(benzyloxy)-B-(2-id | TIN-NMR (SOSIZH «063. 1 ! ! more | oxy-2-methylpropyl)amine | (Nu; 0882) .

S she I | with. Gen 535 (on tu YN) (E 0 | iprvecyclopropyl-o-methy 5.95 (18), 633 (1H), 7.321 ! em ! ! m | luenzamid o- TV1 (6НЙ 763 (НН), 784 (2Ну rot Tue e 119! ! MMu detected - 486,

MU av and | MUH calculated x 455.6

KD KI | M-cyclopropyl-ia-IV-SHI- VT IV : what | duxidotetrahydrothiophene | MU revealed xx 5506 and i re va n | "Zl)mety amino Kb-(3-4t | MU calculated x 548.6 : ше У и шо. е и !

Y and shk sh 7 and srphenoxyimidazoi 1.2-01p1 | ! y 3 Ityadazine-z-yl 2-methyloben a-y ' amide shi 2 | And! ask pot el t p t HO p o p oto pon vv ots vvv 328 | B | Mucyclopropyl-i-18-(Zavt | 1H-NMR (SOSIZK -- VI: g. ii | orphenoxy)-8-(tetrahydro | (2H); 0.88 (2H), 1.69 (1H). sh: MH ! and

And Ak furan-z-ipmetitaminoiimi | 2.19 (IN), 2.32(3Н), ЗВ в в | dazogy2-b)pyridazin-ya- (IN), 280 (1), 3.32 (ZNU. p; ip-2-methylbenzamide | 3.72 - 4004), oral:

With | I W o. with : | | MUU was detected ex 502.6; MUU is calculated at 2,501.6,329 | hoo me! I stlosroni via nt 119

On: 1 and o rphenoxy) 8 1xmethyl-ze | MUU was found to be 528.6

XX Ka n / oxopyrrolidine-Z-yl)methini | MM calculated « 528.8

Co. aminoimidazog 2-1 both | aminosmidase 12-rypyride 3 zin-Z-ip -methybenzamium she mesh

Y dn 01000 Short it pn ny lym V pani (zo oh | Micycloprolip-a 843.3 | 1H-NMR (SOSIZH "500. t | difluorocyclobutylumetigi | HO; b,via H), 2.33 (Z) , he sbchet, amino 8443-fluorophenoxy 2.39 (2, 2.1 (2

And Y imidazog!,2-rIpyridazin-3- (- 2.95 (3), 348 (28), yiv, | ily-e-methylisenzamide, | 57) 51) 827 ok | Is it? - 7.07 (ZNU;

BO 725(N)U 738 YN), 760. (18), 7,722) mouth still | I you

MU; 8236 detected

IAM calculated " 521.6 ! zi Coplotopiachvottia |name (methe cho | roxy-2-methylpropyl)amine (052 (nu 077 (ene, ie | oi8-o-methoxyethyl)amine | (2H), 1.28 (vn). 238 an and | orimidazoi 1,2 Oiptridazine- (2,vy (SY), ZY. ON), head.

Hu : Zylro-methylbenzamide (en, Za en) zv en), ! H kerosene H 1 H in! iy | (5at IN), Be? (IN) vv. she GIn) tiB on), 726 (1), ! 744 IN) 77 IN) your. what | | anuvrt še | eater

MU detected x 453 5 00 days - 20 0 and (MMK calculated x 4526 (332 sleep | Mecyclopropyl-a-(8-Cso-hyde) (NYAM (DM) more

Sh and | roxy-2-methylpyroyl)amine (2), 0.70 (2), 1.27

With br | orb-(pyridine-i yloxysmid ((6H), 2.42 (ZH), 2.85 (1H), nn ra | azo1,2-bipyridazin-3-za (2), 482 (IN), 6.32 lu pEya | ipr2-methybenzamium | (2H), 85691) 740 YN, oi | | 742 pn), tvz (Nu Vy (yn vovnu, 32 (2). 8.34 (1H) рrt yat-ova

MM found 473.6 0000000 Mu calculated and read by Stueuv 00000000 pressed 00000000 Analyzed 0000 zaz | pos os pe on sho | roxy-2-methylpropylamine | MUM was detected x 489.6 she Ko; | about (pyridine and ipsulfani | MA calculated - 488.6

C | pmidaoi 1,9-0Ipyridazine: and p: | Zp) -2-methylbenzamide tire nn 334 | . in Mecyclopropyl-448-2-hyde CT 1.05

And he | roxy-2-methylpropyl)vmin | MUU was detected "х 485.6 and ХК, 1 | oi-bya«pyridine-2-ipsulsrani | MUU is calculated - 488.6 a! pimidazogy2-vipridazine-

Ak LO Zapro-methylbenzamide oy oo za ni nn nn pn sten o pyun PO nin o rn 335 on | Mecyclopropyl-ia-8-ethide | 1N-AYAME. (MOVU set na | roxy-2-mathylyropylamine | 0.51 (2H), 0.85 (2), 13 a be | oi-b-stetrahydro-?H-pyran- | (n) 1.65 (2H) 208 (28). not | d-ylsulfanipimidazoi! 2- 12.38 (ZNU 281 (1) 322 ie | Bipyridazin-3-en) zat OH); 397 (2n) p.; | ipi-2-methypibenzamid al (nu, 514 IN), ze o InugZ5 (IN) 7989 (2H), tetinuvovynuroto vte 1.09

MUM was found x 4967 et retttuttttttpno nV z38 | he | 4-(6-(cyclopentylsulfa | 1H-YAME (MBO) i y | nipu8-Co-pdroxy- methyl O,5o (2), 055 anu 113 p. ho | propyl)amichoimidazogy 2-5 (inh 153 - 176 ( vn. i y / Ipyridazine-3- | 2.20 (2). 2.35 (ZN), 2.80 y y | iluModyklopropipo-methiarin 321 СН, 409 рn y. | pbenzamide Galan, vis yn), vv yn taz Nu tvo ON) (te In), vovnu, Vo.

ОН) ррт вте 31

Pryka | Ormyav structure: Analytical data

And | MA was calculated to be 479.7 (3857 | y | KEcycloporogyl-yaa-No-pd | yan-yaMR FMS Ce and | oxy-2-methylpropyl)amine 0.50 (OH), 0.65 (2H); 118! the bottom we drink and ! and not that P, | o1b4piperidin-y-yl)imidase (BNO, 1.58 (6H), 2.27 (NU, and their | o11.2х0)pyridazin-3- c235(3H), 2.78 ІН), 328, ! I would p. Cheek from the | ipu-2-methyloenzamide (2) 47518), 807 YN «Ш

M | own (1), 7.33 (IN), 7.86,

CH), 7.98 (1), 803, 827 (1Н) ppm

Tuesday 18 1! MU was detected x 453.5

Sh MUU is calculated - 452.6

The following examples of compounds were prepared analogously to the procedure described in example 101, using the appropriate intermediate compound and argyboronic acid rilyopod BioskK (data

LC-MS, such as retention time (CT in min) or mass peak observed, were collected using LC-MS Method A unless otherwise noted:

At | The structure of the name Analytical data p p p p p p o p o p o p o p o p o p o p o p o p o p o (vte2077 an | 4-8-(azetidin-zimethyluaminoi che | MU was found -

What | di | "Hydroxymethylifenikimidazogi 2-81 G483.5

ИЗ 01 et Я | and and more Z | pividazine-Z- | MM 7 in | and Aecycloprolyl-d-methybenzamide ' calculated - and | th ravine:

M | (va voi | yin zro I tert-butyl ovt- 24

And | . and and in | With (cyclopropylcarbamoyl)--m and MUU was found - . . Also, I o M ethylphenyl 6-(2-(hydroxymethylpheni I 583.7 ! zeing ut ia women, le | pymidazoi1.2-v|pyridazinea- | MU : ! - IJ Z | iamino)methyp|azetidine- | calculated - ksevny N y i y u. | 1-karbosypat | VIT

Prykp, ribbon | Name | Analytical data! with Ya and Mon t s | | dte iz in this | M-cyclopropyl-4-(8-P(4-pdroxy-4-m | MM was found to be zi | o. sho. Epicyclohexylmethyliamino)v-2 | 540.7 enro zm Me ! | What I I and is G : | tidoxymethylrheniutimidase 1.2-bipi | MU o s | ! . ' ! | ma | ridazine-3-yl-2-methyloenzamide | calculated by

N that I: still | | 539.7

SHE B I

BU | | yat- 105

CA | Mecyclopropiony B (3-hydrocois-me | MM detected - Bacon SHY ion. that m r Fi U | typbutyl)aminoyY-642-tihydroxymethyl) | 500.6

I still have cancer Phenyl|midazolii,2-Bipyridazine-3- | MU ' and no vn and mre-methyloenzamide | calculated w y

How | | BGN 9.6 what! Her naya

OH | | bodybuilder

M nn | (K5)-M-cyclopopraptyl-44842-hydroxy | MUM was detected - schu schi - ik methylphenyliv-(4-podroxypentyl)v 500.5

With uncle ; mino|imidazoi1,2-VIpyridazine-Z- | MOOOO! | I and : ho in I pu methypbenzamide calculated 5 more | 499.6

I. is not! SHI

VI | and,

Go. V shy vn od tiv | ЯК) -Metsikpopropyl-448--podroxy» MU was detected by | pd Co; | Zsmetipbutylamino v-2-(podroxime 1 5006 : och | M i ! she sche r. " | ethylphenylimidazog! 2-bipyridazine-ya | MU : ! M ! : i ! y | "ipre-methypbenzamide | calculated in avav 2 | 1 nn a

Application | Structure Name | Analytical data | W: 096 no | M-cyclopropia-4-(6-12-(hydroxymeth: ! kN I | | | MUM was found "and ! sne Its in | puphenylv-(1-methyl-oka hg ha I pocoopioolivinoZlinoimidya, z4 | schi y in | oxopyrrolidine-Z-yl)methyliaminamide | MM ! ! i ! | i i Ba i i | zo/1,2-vipyridazine-Z-ily-o-methylbenz | | I : | seh B | calculated t i I- What are you doing?

And ). | And! | scha | (KBIMcyclopropylaya Vo tidroxy | MU was found « ! NOM and ! I V zach | r. ie; | methyl)phenyl-84(tetrahydrofuran-Z- | 498.6

S r; | ylmethyliamino midazogy, 2-bitiridase | Mu! | : in in | nempre-methypoenzamide calculated - m; and she shi 497.6 nyshshshshi shishishinsh nn

INYAMRO S

: ((rmeoyaYavu o (o5e (2H), 0.88 (Gen 144 (zn). (78 nu 209 anu zat (zn), zvo (in), Za shk; | | what she | onu ZA (B), un | Mecyclopropyl-a-(8-2-(hydroxymeth 402 (2), my and

For g: li N N y : ! S v r | methyl)aminoimidazoI 1,2-VIpyridazine-| 822 (1), 538 and, | Zchpug-methylbenzamide anu 7.28 (nu. and san Y that tav o iNU tive) 1 ! to

Sen 750 (on),

ОТвО(2NIrot

And Tuesday" 108

MM was discovered - led by | vm calculated --

pp znin MO t po p p p po i sys pyv i t p sti

And Prikia, ! Structure | The name of IANAyetic data of yr

UNO INN Po pov and 347 7th | 448-(2-cyanoethyl)amino-8(3-fluoro (tya 118

G | enoxyimidazoi 1,2-bipyridazine-Z-| MUM detected 5) ! ! NK of the city! | : ; ! greyl MUcyclopropnio-methyloenzamide | 4715

KE! . ! : | uche usual | And MU: and! om : ! and: ro. and | calculated and | And "at0.5! : KE

Eat! : 1нН-яЯМе !

She and she !

OMeOchavu t, omu (2n), 083 : i še | well, look (ZNU p27v in zav (in), 365 (ZNU v2v (1), 707. (720 (ZNU toB;

And and! . 4 beds, 748 beds. yav in 76 and : and In sshcha (EN), 78? well open (NU 822 nn nn cos

Example 348 4-16-K4-chloro-2-fluorophenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y"-M-cyclopropyl- 2-methylbenzamidon on vm / TU-k nim / o H c on 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b |pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 4-chloro-2-fluoroaniline, obtaining after treatment and purification 3.1 mg (C 95) of the compound indicated in the title. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.65 (2H), 1.18 (6H), 2.31 (ZH), 2.79 (1H), 3.16 ( 2H), 4.79 (IN), 6.15 (1H), 6.59 (1H), 7.19 (1H), 7.31 (1H), 7.43 (1H), 7.77 (1H ), 7.79 (1H), 7.95 (1H), 8.15 (1H), 8.27 (1H), 8.63 (1H) ppt.

Example 349

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(5-methoxy-2-methylphenyl)amino|imidazo(1,2-b|Ipyridazin-3-yl-2 -methylbenzamid on on on /Fo

Ve zm 7 -- НМ зии уху уху ухой 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazine- 3-yl)y"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305, using 5-methoxy-2-methylaniline, obtaining after treatment and purification 9.1 mg (10 95) of the title compound. 1H-NMR (0M50-ab): b- 0.48 (2H), 0.64 (2H), 1.18 (6H), 2.17 (ZH), 2.22 (ZH) , 2.78 (1Н), 35.16 (2Н), 3.62 (ЗН), 4.81 (1Н), 6.04 (1Н), 6.43 (1Н), 6.56 (1Н), 7.08 (1H), 7.20 (1H), 7.34 (1H), 7.80 (1H), 7.85 (1H), 7.88 (1H), 8.02 (1H), 8 .23 (1H) ppt.

Example 350

M-cyclopropyl-4-76-(4-fluoro-2-(hydroxymethyl)phenyl|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl) u.2-methylbenzamide

And I

In b

MN MN u/Fe a) ve / - zm /

E r sn LC on on 50 mg (104 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)u" M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 1, using 14-fluoro-2-(hydroxymethyl)phenyl|Iboronic acid, obtaining after treatment and purification 10.4 mg (18 Fo) of the title compound. 1H-NMR (0M50-ab): b- 0.48 (2H), 0.64 (2H), 2.34 (3H), 2.67 (2H), 2.79 (1H) , 3.61 (2H), 4.65 (2H), 5.34 (1H), 6.36 (1H), 7.20 (1H), 7.33 (1H), 7.41 (1), 7.59 (1H), 7.67 (1H), 7.91 (1H), 7.95 (1H), 8.01 (1H), 8.27 (1H) ppt.

Example 351

M-cyclopropyl-4-16-((3,5-difluorophenyl)amino|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u. 2-Methylbenzamidone /F /Fo vm / -0U-x nim / r g ro oy 75 mg (164 μmol) 4-/6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo (1,2-B|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305, using 3,5-difluoroaniline, to obtain after treatment and purification 4, 9 mg (6 95) of the title compound. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.66 (2H), 1.18 (6H), 2.35 (3H), 2.81 (1H), 3.17 (2H), 4.80 (IN), 5.87 (1H), 6.67 (1H), 6.73 (1H), 7.30-7.39 ( ЗН), 7.77 (1Н), 7.79 (1Н), 8.01 (1Н), 8.91 (1Н), 9.40 (IN) ppt.

Example 352

M-cyclopropyl-4-16-(2,3-difluorophenyl)amino|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u.2 -methylbenzamide on on

Fo Fe vm / Ch-k nmbm' y / ve r ! 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(/1,2-b|pyridazin-3-yl)"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 2,3-difluoroaniline to give, after work-up and purification, 4.3 mg (5 95) of the title compound.1H-NMR (0M5O-46) : b- 0.49 (2Н), 0.65 (2Н), 1.18 (6Н), 2.30 (ЗН), 2.79 (1Н), 3.17 (2Н), 4.80 (1Н ), 6.16 (1H), 6.62 (1H), 7.02 (1H), 7.12 (1H), 7.28 (1H), 7.80 (2H), 7.92 (1H) , 8.00 (1H), 8.27 (1H), 8.77 (IN) ppt.

Example 353

M-cyclopropyl-4-/6-((3-fluoro-4-methoxyphenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y- 2-methylbenzamido on Ge)

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazine) -3-yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305, using 3-fluoro-4-methoxyaniline, obtaining after treatment and purification 16.8 mg (1995 ) of the title compound. 1H-NMR (0M50O-ab): b- 0.50 (2H), 0.66 (2H), 1.18 (6H), 2.35 (3H), 2.681 (1H), 3.15 (2H), 3.77 (ZH), 4.680 (1H), 5.82 (1H), 6.55 (1H), 7.06 (1H), 7.21 (1H), 7.32 (1H), 7.70 (1H), 7.75 (1H), 7.83 (1H), 8.04 (1H), 8.29 (1H), 8.91 (1H) ppt.

Example 354

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-((4-methoxyphenyl) amino|imidazo|(1,2-b|pyridazin-3-yl)u.2 -methylbenzamidon on s s ve / -090-k nim" /

75 mg (164 μmol) 4-/6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-B|pyridazin-3-yl)" M-Cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate Example 9ba, was converted analogously to Example 305 using 4-methoxyaniline to give, after work-up and purification, 11.4 mg (13 95) of the title compound. 1H-NMR (0M5O -46): b- 0.51 (2Н), 0.66 (2Н), 1.18 (6Н), 2.37 (ЗН), 2.81 (1Н), 3.14 (2Н), 3, 70 (ZH), 4.680 (1H), 5.83 (1H), 6.46 (1H), 6.86 (2H), 7.33 (1H), 7.55 (2H), 7.75 (1H ), 7.85 (1H), 810 (1), 8.29 (1H), 8.71 (1H) ppt.

Example 355 4-16-KZ-chlorophenyl)amino|-8-(2-hydroxy-2-methylpropyl)amino|imidazo

P,2-Shipyridazin-3-yl)y-N-cyclopropyl-2-methylbenzamidone

Pho / Pho

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazine- 3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 3-chloroaniline, obtaining after treatment and purification 15.4 mg (18 95) of the title compound. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.66 (2H), 1.18 (6H), 2.36 (ZH), 2.81 (1H), 3.16 ( 2H), 4.80 (1), 5.88 (1H), 6.64 (1H), 6.92 (1H), 7.27 (1H), 7.36 (1H), 7.71 (1H ), 7.58 (1H), 7.83 (1H), 7.93 (1H), 7.95 (1H), 8.28 (1H), 9.15 (1H) ppt.

Example 356

M-cyclopropyl-4-16-(2,4-difluorophenyl)amino|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u.2 -methylbenzamide on on

Fo Fe viti -0-k bottoms

Kk F on y on 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl -2-methylbenzamide, which was prepared according to Intermediate Example 9ba, was converted analogously to Example 305 using 2,4-difluoroaniline to give, after work-up and purification, 5.0 mg (6 95) of the title compound. 1H-NMR (0M5O- ab): b- 0.50 (2Н), 0.65 (2Н), 1.18 (6Н), 2.28 (ЗН), 2.79 (1Н), 3.14 (2Н), 4.680 (IN ), 6.06 (1H), 6.54 (1H), 7.04 (1H), 7.27 (1H), 7.30 (1), 7.78 (1H), 7.79 (1H) , 7.94 (1H), 7.99 (1H), 8.25 (1H), 8.48 (1H) ppt.

Example 357

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-2-ylamino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo| 1,2-b|pyridazin-3-yl)'M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using pyridin-2-amine, yielding after treatment and purification 10.1 mg (12 95) of the title compound. 1H-NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 1.18 (6H), 2.39 (3H), 2 .81 (1H), 3.16 (2H), 4.80 (1H), 6.27 (1H), 6.60 (1H), 6.91 (1H), 7.36 (1H), 7, 69 (1H), 7.80 (1H), 7.86 (1H), 8.01 (1H), 8.08 (1H), 8.23 (1H), 8.31 (1H), 9.48 (1H) ppt.

Example 358

M-cyclopropyl-4-[6-((4-fluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide and EI

In U

MN MN

75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl) y"N-Cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305 using 4-fluoroaniline to give, after work-up and purification, 20.1 mg (24 95) of the title compound. 1H-NMR (0М5О-46): 6- 0.52 (2Н), 0.66 (2Н), 2.37 (ЗН), 2.68 (2Н), 2.81 (1Н), 3.49 (2Н), 5.79 (1), 7.11 (2H), 7.28 (1H), 7.35 (1H), 7.65 (2H), 7.77 (1H), 7.84 (1H), 8 .04 (1H), 8.29 (1H), 8.98 (1H) ppt.

Example 359

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-3-ylamino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide he he

Fo Fe viti Y -0-k nyu zni

Z r oy 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)u"M -cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using pyridine-2-amine to give, after work-up and purification, 12.6 mg (13 95) of the title compound. 1H-NMR ( 0М5О-аб): b- 0.51 (2Н), 0.66 (2Н), 1.19 (6Н), 2.39 (ЗН), 2.81 (1Н), 3.17 (2Н), 4 .82 (IN), 5.91 (1H), 6.66 (1H), 7.28 (1H), 7.34 (1H), 7.78 (1H), 7.81 (1H), 8, 06 (1H), 8.11 (1H), 8.13 (1H), 8.31 (1H), 8.80 (1H), 9.13 (1H) ppt.

Example 360

M-cyclopropyl-4-16-(2-fluoro-4-methylphenyl)sulfanyl|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y- 2-methylbenzamidon on ve" / p"-k vm" /

E o | o 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide , which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 2-fluoro-4-methylbenzenethiol to give, after work-up and purification, 43.2 mg (48 95) of the title compound. 1H-NMR (0M5O-46) : b- 0.48 (2Н), 0.65 (2Н), 1.13 (6Н), 2.19 (ЗН), 2.39 (ЗН), 2.79 (1Н), 3.24 (2Н ), 4.72 (1H), 6.29 (IN), 6.97 (1H), 7.00 (1H), 7.14 (1H), 7.25 (1H), 7.52 (1H) , 7.57 (1H), 7.64 (1H), 7.93 (1H), 8.24 (1H) ppt.

Example 361

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(3- isopropoxyphenoxy)imidazo|1,2-b|Ipyridazin-3-yl)y.2-methylbenzamide

Ge) on

Fe /Fove" / -090 o7zm" / p OO c) i A He) and 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1 ,2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 3-isopropoxyphenol, obtaining after treatment and purification 33.3 mg (37 95) of the title compound. 1H-NMR (0M5O-46): b- 0.46 (2H), 0.63 (2H), 1.15 (6H), 1.20 (6H), 2.14 ( ЗН), 2.76 (1Н), 3.27 (2Н), 4.58 (1Н), 4.74 (1Н), 6.14 (1Н), 6.73-6.83 (ЗН), 6 .96 (1H), 7.15 (1H), 7.30 (1H), 7.70 (1H), 7.80 (1H), 7.92 (1H), 8.21 (1H) ppt.

Example 362

M-cyclopropyl-4-16-(2-fluoro-4-methylphenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y. 2-methylbenzamide

And I

In U

MN MN

DUOo-To vm / vm / ov | o 75 mg (15 bmmol) 4-6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)y"N-cyclopropyl-2-methylbenzamide , which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 2-fluoro-4-methylbenzenethiol to give, after work-up and purification, 30.3 mg (34 95) of the title compound.1H-NMR (0M5O-46) : b- 0.48 (2Н), 0.66 (2Н), 2.19 (ЗН), 2.40 (ЗН), 2.64 (2Н), 2.80 (1Н), 3.55 (2Н ), 6.23 (1H), 7.01 (1H), 7.15 (1H), 7.26 (1H), 7.53 (1H), 7.57 (1H), 7.64 (1H) , 7.66 (1H), 7.94 (1H), 8.25 (1H) ppt.

Example 363 4-(6-(4-chloro-2-(hydroxymethyl)phenyl|-8-K2-hydroxy-2-methylpropyl)amino imidazo|1,2-b|Ipyridazin-3-yl)y"-M- Cyclopropyl-2-methylbenzamidone 75 mg (164 μmol) 4-/6-bromo-8-K(2-hydroxy-2-methylpropyl)amino |imidazo(1,2-B|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted similarly to Example 1, using

Id-chloro-2-(hydroxymethyl)phenyl|boronic acid to obtain after treatment and purification 22.5 mg (26 95) of the title compound. 1H-NMR (0M5O-46): b- 0.48 (2H), 0.64 (2H), 1.15 (6H), 2.33 (ZH), 2.79 (1H), 3.31 ( 2H), 4.64 (2H), 4.73 (1H), 5.32 (1H), 6.42 (1H), 7.00 (1H), 7.32 (1H), 7.43 (1H ), 7.51 (1H), 7.65 (1H), 7.91 (1H), 7.95 (1H), 8.00 (1H), 8.26 (1H) ppt.

Example 364 4-(6-(4-chloro-2-(hydroxymethyl)phenyl|-8-(3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y"- M-cyclopropyl-2-methylbenzamide

And I be U

MN MN

Fe F9 vm" / sho zm / uh si uh on oy oy 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b| Ipyridazin-3-yl)'N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 1, using

Id-chloro-2-(hydroxymethyl)phenyl|boronic acid, obtaining after treatment and purification 15.6 mg (18 95) of the title compound. 1H-NMR (0M50-ab): b- 0.48 (2H), 0.64 (2H), 2.33 (ZH), 2.67 (2H), 2.79 (1H), 3.61 ( 2H), 4.64 (2H), 5.35 (1H), 6.37 (1H), 7.32 (1H), 7.43 (1H), 7.57 (1H), 7.65 (1H ), 7.68 (1H), 7.91 (1H), 7.94 (1H), 8.01 (1H), 8.26 (1H) ppt.

Example 365

M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino|-6-(pyridin-4-ylamino)imidazo|1,2-b|Ipyridazin-3-yl-g-methylbenzamidone one

Fo /Fo viti Y -0-k nyu zi s

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl -2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using pyridine-4-amine to give, after work-up and purification, 10.7 mg (14 95) of the title compound. 1H-NMR (0M5O- 46): 6- 0.52 (2H), 0.67 (2H), 1.18 (6H), 2.40 (ZH), 2.82 (1H), 3.18 (2H), 4.81 (1H), 5.95 (1H), 6.77 (1H), 7.38 (1H), 7.59 (2H), 7.81 (1H), 7.83 (1H), 8.06 ( 1H), 8.27-8.35 (ZN), 9.45 (IN) ppt.

Example 366

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-((b-methoxypyridine-

Z-yl)lamino|imidazo|1,2-5|pyridazin-3-yl-2-methylbenzamidone / p"5ox nim" / 7 rechy r o i ra He) Y 75 mg (164 μmol ) 4-/6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-B|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba was converted analogously to Example 305, using 4-methoxyaniline, to give after treatment and purification 27 mg (33 95) of the title compound. 1H-NMR (0M5O-46): b- 0.50 (2H), 0, 65 (2H), 1.18 (6H), 2.36 (ZH), 2.80 (1H), 3.15 (2H), 3.79 zo (ZH), 4.680 (1H), 5.683 (1H) , 6.55 (1H), 6.77 (1H), 7.30 (1), 7.76 (1H), 7.77 (1H), 7.92 (1H), 8.09 (1H), 8.28 (1H), 8.45 (1H), 8.82 (1H) ppt.

Example 367

M-cyclopropyl-4-16-(2-fluoro-5-methylphenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y. 2-methylbenzamide and others

In U

MN MN

DYU 0-X vita nyu zm

IS

A I theo oi oi 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl|-M- cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate Example 247a, was converted analogously to Example 305 using 2-fluoro-5-methylaniline to give, after work-up and purification, 18.7 mg (22 95) of the title compound.1H-NMR (0М5О-46): b- 0.48 (2Н), 0.65 (2Н), 2.23 (ЗН), 2.28 (2Н), 2.68 (ЗН), 2.79 (1Н), 3.48 (2H), 6.10 (1H), 6.79 (1H), 7.09 (1H), 7.24-7.32 (2H), 7.78 (1H), 7.87 ( 1H), 7.90 (1H), 7.94 (1H), 8.25 (1H), 8.47 (1H) ppt.

Example 368 4-(6-anilino-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl-

M-cyclopropyl-2-methylbenzamide

Yi I

In U

MN MN

UV Fe viti -o- low and » OD oi oi 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazine- 3-yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using aniline, to obtain after work-up and purification 21.1 mg (26 95) of the title compound. 1H - NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 2.38 (3H), 2.68 (2H), 2.81 (1H), 3.49 (2H ), 5.84 (1), 6.90 (1Н), 7.23-7.31 (ЗН), 7.34 (1Н), 7.66 (2Н), 7.78 (1Н), 7, 84 (1H), 8.12 (1H), 8.30 (1H), 8.96 (1H) ppt.

Example 369

M-cyclopropyl-4-16-((2-fluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide EY

In U

MN MN du Au-ud

Ve zm / nyu zm /

E. i. 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl))"M -cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate Example 247a, was converted analogously to Example 305 using 2-fluoroaniline to give, after work-up and purification, 12.0 mg (14 95) of the title compound. 1H-NMR (0M5O- 46): b- 0.50 (2Н), 0.65 (2Н), 2.32 (ЗН), 2.68 (2Н), 2.80 (1Н), 3.49 (2Н), 6.14 (1), 7.00 (1H), 7.14 (1H), 7.23 (1H), 7.26-7.34 (2H), 7.79 (1H), 7.81 (1H), 8.02 (1H), 8.17 (1H), 8.27 (1H), 8.57 (1H) ppt.

Example 370

M-cyclopropyl-4-(6-C2-(hydroxymethyl)phenyl|amino)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2 -B|Ipyridazin-3-yl)-2- methylbenzamide and i

RU U

MN MN

DU

Ve zm / nyu zm /

75 mg (156 μmol) of 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)yl) M-Cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305 using (2-aminophenyl)methanol to give, after work-up and purification, 5.2 mg (6 95) of the title compound. NMR (0M50-ab): b- 0.49 (2H), 0.64 (2H), 2.25 (3H), 2.69 (2H), 2.78 (1H), 3.50 (2H) , 4.55 (2H), 5.30 (1H), 5.94 (1H), 7.05 (1H), 7.18-7.29 (ZH), 7.38 (1H), 7.77 -7.687 (ZH), 8.01 (1H), 8.07 (1H), 8.24 (1H) ppt.

Example 371

M-cyclopropyl-4-76-|(3-fluoro-5-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazin-3-yl)u-2-methylbenzamide I

In U

МН МН с с вм" / - nim" / r дхрой ой 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2- b|Ipyridazin-3-yl)u"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using 3-fluoro-5-methylaniline, obtaining after treatment and purification 20.2 mg (23 95) of the title compound. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.66 (2H), 2.25 (ЗН), 2.35 (ЗН), 2, 68 (2H), 2.81 (1H), 3.49 (2H), 5.82 (1H), 6.53 (1H), 7.05 (1H), 7.29-7.39 (2H) , 7.54 (1H), 7.77 (1H), 7.87 (1H), 7.98 (1H), 8.30 (1H), 9.12 (1H) ppt.

Example 372 4-16-K4-chloro-3-fluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazin-3-yl)y-N-cyclopropyl-2-methylbenzamide and I

In U

MN MN co

75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2- b|Ipyridazin-3-yl)"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305 using 4-chloro-3-fluoroaniline, yielding after work-up and purification 16.9 mg ( 19 95) of the title compound. 1H-NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 2.36 (3H), 2.68 (2H), 2.81 (1H), 3.50 (2H), 5.81 (1), 7.26 (1H), 7.35 (1H), 7.39 (1H), 7.44 (1H), 7.77 ( 1H), 7.80 (1H), 7.95 (1H), 7.98 (1H), 8.91 (1H), 9.36 (1H) ppt.

Example 373

M-cyclopropyl-4-16-((3,4-difluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-B|pyridazin-3-yl)-2- methylbenzamide and EI

In U

MN MN

Fe chen Fo viti n zum r gr o n i on 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin- 3-yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using 3,4-difluoroaniline, obtaining after treatment and purification 11.9 mg (14 95) of the indicated in 1H-NMR (OM5O-ab): b- 0.51 (2H), 0.66 (2H), 2.36 (3H), 2.68 (2H), 2.81 (1H), 3 .50 (2H), 5.79 (1), 7.22 (1H), 7.28-7.39 (ZH), 7.77 (1H), 7.81 (1H), 7.91 (1H ), 8.00 (1H), 8.30 (1H), 9.20 (1H) ppt.

Example 374 4-(6-K4-chlorophenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazoi|1,2-B)pyridazin-3-yl)y"-M-cyclopropyl-2 -methylbenzamide and EI

In U

МН МН pra 4 д я ой с ой 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl) )y"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305 using 4-chloroaniline, obtaining after work-up and purification 14.3 mg (17 95) of the title compound. 1H- NMR (0M5O-46): 6- 0.52 (2H), 0.67 (2H), 2.38 (3H), 2.68 (2H), 2.81 (1H), 3.49 (2H) , 5.82 (IN), 7.30 (2H), 7.33 (1H), 7.38 (1H), 7.68 (2H), 7.78 (1H), 7.84 (1H), 8.02 (1H), 8.30 (1H), 9.12 (1H) ppt.

Example 375

M-cyclopropyl-4-/6-|(5-fluoro-2-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl) y-2-methylbenzamide

E E

E E

In U

MN MN

DU Co

75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazine-3 - yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using 5-fluoro-2-methylaniline, obtaining after treatment and purification 6.6 mg (8 95) indicated in of the title compound. 1H-NMR (0M50-abb): 0- 0.49 (2H), 0.64 (2H), 2.24 (ZH), 2.26 (ZH), 2.63-2.85 ( ЗН), 3.50 (2Н), 6.11 (1Н), 6.75 (1Н), 7.19 (1Н), 7.24 (1Н), 7.29 (1Н), 7.78-7.86 (ZH), 7.96-8.03 (2H), 8.25 (1H) ppt.

Example 376 4-16-K4-chloro-2-fluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo

N,2-Shipyridazin-3-yl)-N-cyclopropyl-2-methylbenzamide and EI

In U

MN MN

/Fe se DK viti ny zum

E ich r Ov o y s o y 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)u) "M-Cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305 using 4-chloro-2-fluoroaniline, obtaining after treatment and purification 10.8 mg (12 95) of the title compound. 1H-NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 2.31 (3H), 2.68 (2H), 2.80 (1H), 3.49 ( 2H), 6.12 (1H), 7.21 (1), 7.32 (1H), 7.35 (1H), 7.46 (1H), 7.79 (1H), 7.680 (1H), 7.96 (1H), 8.18 (1H), 8.28 (1H), 8.69 (1H) ppt.

Example 377 4-16-Kb-chloro-2-methylphenyl)amino|-8-(3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y"-M-cyclopropyl -2-methylbenzamide and EI

In U

MN MN

/Fe se DK vy ty n y zum r water oy oy oy oy 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazine-3 - yl)u"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using 5-chloro-2-methylaniline, obtaining after treatment and purification 9.7 mg (11 95) of the specified in the title compound. 1H-NMR (0M5O-46): b- 0.48 (2H), 0.64 (2H), 2.24 (ЗН), 2.26 (ЗН), 2.70 (2Н), 2.78 (1H), 3.50 (2H), 6.06 (1H), 7.00 (1H), 7.21 (1H), 7.26 (1H), 7.29 (1H), 7.683 (1H), 7.89 (1H), 7.91-7.95 (2H), 8.04 (IN), 8.23 (1H) ppt.

Example 378

M-cyclopropyl-4-16-((3,5-difluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-B|pyridazin-3-yl)-2- methylbenzamide and EI

In U

MN MN

75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazine- 3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305 using 3,5-difluoroaniline, obtaining after work-up and purification 14.7 mg (17 95) of the title compounds. 1H-NMR (0M5O-ab): b- 0.50 (2H), 0.66 (2H), 2.35 (3H), 2.68 (2H), 2.81 (1H), 35, 51 (2H), 5.80 (1H), 6.69 (1H), 7.31-7.38 (ZH), 7.43 (1H), 7.78 (1H), 7.79 (1H ), 8.00 (1H), 8.91 (1H), 9.43 (1H) ppt.

Example 379 4-(6-CH-chlorophenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-B)pyridazin-3-yl)y"-M-cyclopropyl-2 -methylbenzamide and EI

In U

MN MN

/Fe se DK development of the mixture roo oy oy 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazine-3 - yl)u"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using 3-chloroaniline, obtaining after treatment and purification 16.7 mg (19 95) of the title compound. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.66 (2H), 2.36 (ZH), 2.68 (2H), 2.81 (1H), 3.50 ( 2H), 5.82 (1), 6.93 (1H), 7.28 (1H), 7.32-7.39 (2H), 7.50 (1H), 7.79 (1H), 7 .83 (1H), 7.92 (1H), 7.94 (1H), 8.28 (1H), 9.18 (1H) ppt.

Example 380

M-cyclopropyl-4-16-(2,3-difluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-B|pyridazin-3-yl)-2-methylbenzamide and EI

In U

MN MN

/Fe se DK development of ver e roi oy 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazine -3-yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using 2,3-difluoroaniline, obtaining after treatment and purification 6.6 mg (8 95) of the specified in the title compound. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.65 (2H), 2.31 (3H), 2.68 (2H), 2.80 (1H), 3.50 (2H), 6.13 (1), 7.02 (1H), 7.13 (1H), 7.28 (1H), 7.37 (1H), 7.79 (1H), 7 .81 (1H), 7.95 (1H), 7.99 (1H), 8.28 (1H), 8.81 (1H) ppt.

Example 381

M-cyclopropyl-2-methyl-4-16-3-(propan-2-yloxy)phenoxy|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3- il)ibenzamid and EI

In U

MN MN

UV Fovity iom" / rema d o y ac o y 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazine -3-yl)"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 3-isopropoxyaniline to give, after work-up and purification, 4.8 mg (5 95) of the title compound 1H-NMR (0M5O-46): b- 0.46 (2H), 0.63 (2H), 1.21 (6H), 2.14 (ZH), 2.67 (2H), 2.76 (1Н), 3.58 (2Н), 4.58 (1Н), 6.09 (1Н), 6.75-6.84 (ЗН), 7.15 (1Н), 7.91 (1Н), 7.66 (1H), 7.70 (1H), 7.79 (1H), 7.93 zo (IN), 8.21 (1H) ppt.

Example 382

M-cyclopropyl-4-16-((4-fluoro-3-methylphenyl)amino|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)u -2-methylbenzamide

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2- b|pyridazin-3-yl)"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305, using 4-fluoro-3-methylaniline, to obtain after work-up and purification 16.5 mg ( 19 95) of the title compound. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.66 (2H), 1.18 (6H), 2.18 (3H), 2.34 (ЗН), 2.81 (1Н), 3.15 (2Н), 4.80 (1Н), 5.84 (1Н), 6.52 (1Н), 7.02 (1Н), 7.34 ( 1H), 7.44-7.51 (2H), 7.75 (1H), 7.92 (1H), 7.96 (1H), 8.27 (1H), 8.83 (1H) ppt.

Example 383

M-cyclopropyl-4-16-(2-fluoro-5-methylphenyl)amino|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y- 2-methylbenzamide

Ge) on

Fe /Fo viti 0-kh nu

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M -cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 2-fluoro-5-methylaniline to give, after work-up and purification, 10.5 mg (12 95) of the title compound. NMR (0М5О-46): b- 0.48 (2Н), 0.65 (2Н), 1.18 (6Н), 2.23 (ЗН), 2.28 (ЗН), 2.79 (1Н) , 3.15 (2H), 4.79 (1H), 6.13 (1H), 6.52 (1H), 6.79 (1H), 7.09 (1H), 7.27 (1H), 7.78 (1H), 7.86 (1H), 7.88 (1H), 7.95 (1H), 8.25 (1H), 8.42 (1H) ppt.

Example 384

M-cyclopropyl-4-76-(2-fluorophenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamidone one

Fe /Fo ve / 0-x nim /

It contains 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M- cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 2-fluoroaniline to give, after work-up and purification, 8.3 mg (10 95 ) of the title compound. 1H-NMR (0M5O-ab ): b- 0.50 (2Н), 0.65 (2Н), 1.18 (6Н), 2.31 (ЗН), 2.80 (1Н), 3.16 (2Н), 4.79 ( 1H), 6.17 (1H), 6.54 (1H), 7.00 (1H), 7.14 (1H), 7.22 (1H), 7.28 (1H), 7.78 (1H ), 7.81 (1H), 8.02 (1H), 8.14 (1H), 8.27 (1H), 8.52 (1H) ppt.

Example 385

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino1|-6-|(3-isopropylphenyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u.2 -methylbenzamide

He) on web / -90-k nim" / о о ой 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b| pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305, using 3-isopropylaniline, to obtain, after work-up and purification, 11.6 mg (14 95) of the title compound compounds 1H-NMR (0M50-ab): 0- 0.50 (2H), 0.66 (2H), 1.16 (6H), 1.18 (6H), 2.37 (ZH), 2.74- 2.87 (2H), 3.15 (2H), 4.79 (1H), 5.89 (1H), 6.51 (1H), 6.79 (1H), 7.18 (1H), 7 .26 (1H), 7.32 (1H), 7.68 (1H), 7.76 (1H), 7.93 (1H), 8.02 (1H), 8.28 (1H), 8 .84 (1H) ppt.

Example 386

M-cyclopropyl-4-(6-C4-(2-hydroxyethyl)phenyl|amino)-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-5|pyridazin-3-yl)- 2-methylbenzamidone and MH seste u/Fo - -k them /

Ve M ikh r u Ye

M o n o n Fn 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M- cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate Example 9ba, was converted analogously to Example 305 using 2-(4-aminophenyl)ethanol to give, after work-up and purification, 10.6 mg (13 95) of the title compound.1H-NMR (0М5О-46): 6- 0.52 (2Н), 0.66 (2Н), 1.18 (6Н), 2.38 (ЗН), 2.64 (2Н), 2.81 (1Н), 3.15 (2H), 3.54 (2H), 4.57 (1H), 4.80 (1H), 5.87 (1H), 6.49 (1H), 7.10 (2H), 7 .34 (1H), 7.55 (2H), 7.76 (1H), 7.84 (1H), 8.12 (1H), 8.91 (1H), 8.82 (1H) ppt.

Example 387

M-cyclopropyl-4-76-((3-fluoro-2-methylphenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u .2-methylbenzamide

And I

In U

MN MN

Fe /Fe vm / -о- vm /

OD ой ой 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was prepared according to Intermediate Example 247a, was converted analogously to Example 51 using 3-fluoro-2-methylbenzenethiol to give, after work-up and purification, 35.3 mg (42 95) of the title compound. 1H-NMR (0M5O -46): b- 0.49 (2H), 0.65 (2H), 2.18 (ЗН), 2.27 (ЗН), 2.62 (2Н), 2.79 (1Н), 3, 54 (2H), 6.19 (1H), 7.06 (1H), 7.30-7.42 (2H), 7.48 (1H), 7.55 (1H), 7.65 (1H) , 7.68 (1H), 7.95 (1H), 8.24

Z0 (IN) ppt.

Example 388

M-cyclopropyl-4-16-((2-methoxyphenyl)amino1|-8-(3,3,3-trifluoropropyl)amino imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide and and

In U

MN MN

Фе /Фо вый о | 200 mg (415 μmol) 4-(6-bromo-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-5|pyridazin-3-yl)y"N-cyclopropyl -2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305 using 2-methoxyaniline to give, after work-up and purification, 68.3 mg (31 95) of the title compound. 1H-NMR (0M50-a6) : 0- 0.51 (2H), 0.65 (2H), 2.35 (ЗН), 2.69 (2Н), 2.80 (1Н), 3.29 (ЗН), 3.49 (2Н ), 6.28 (1H), 6.87-7.05 (ZH), 7.21 (1H), 7.31 (1H), 7.78 (1H), 7.84 (1H), 8, 02 (1H), 8.09 (1H), 8.24-8.32 (2H) ppt.

Example 389

M-cyclopropyl-2-methyl-4-16-(2-(methylamino)phenoxy|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl) Ibenzamide and i

In U

MN MN

ХХО-ДК vy ros" / ше ой ой 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3- yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51, using 2-(methylamino)phenol, to obtain, after work-up and purification, 35.1 mg (43 95) of the title compound compounds. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.65 (2H), 2.33 (3H), 2.46 (2H), 2.80 (1H), 3, 25 (2Н), 3.29 (ЗН), 5.21 (1Н), 6.84 (1Н), 6.95 (1Н), 7.06 (1Н), 7.14 (1Н), 7.19 (1H), 7.31 (1H), 7.82 (1H), 8.04 (1H), 8.09 (1H), 8.26 (1H), 9.54 (1H) ppt.

Example 390

M-cyclopropyl-4-/6-(5-fluoro-2-methylphenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y-2- methylbenzamide and i

In U

MN MN

Fo Fe vy --IO-om / r s r roy oy 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b| Ipyridazin-3-yl)'M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51, using 5-fluoro-2-methylphenol, obtaining after treatment and purification 31.5 mg (38 95 ) of the title compound. 1H-NMR (0M5O-46): b- 0.46 (2H), 0.63 (2H), 2.10 (6H), 2.69 (2H), 2.76 (1H ), 3.60 (2H), 6.16 (1), 7.07 (1H), 7.13 (1H), 7.18 (1H), 7.37 (1H), 7.60 (1H) , 7.69 (1H), 7.72 (1H), 7.93 (1H), 8.21 (1H)

C0 ppt.

Example 391

M-cyclopropyl-4-76-(5-fluoro-2-methylphenoxy)-8-|((2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y). 2-Methylbenzamidonone / Phove" / -0-k om" / r ode oy oy oy oy oy oy oy oy oy oy 50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo |1,2-b|pyridazin-3-yl)'M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51, using 5-fluoro-2-methylphenol, with the result after treatment and purification 29.4 mg (54 95) of the title compound 1H-NMR (0M5O-ab): b- 0.46 (2H), 0.73 (2H), 1.17 (6H), 2.10 (6H ), 2.76 (1H), 3.28 (2H), 4.76 (1H), 6.20 (1H), 6.98 (1H), 7.06 (1H), 7.13 (1H) , 7.17 (1H), 7.36 (1H), 7.61 (1H), 7.71 (1H), 7.92 (1H), 8.21 (1H) ppt.

Example 392 4-(6-C4-chloro-2-(hydroxymethyl)phenyl|sulfanyl)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)- M-cyclopropyl-2-methylbenzamide

And I

In U

MH MH vit onov / on c on 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl) "M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using (5-chloro-2-sulfanylphenyl)methanol, obtaining after treatment and purification 49.0 mg (55 95) of the indicated 1H-NMR (OM50-ab): b- 0.48 (2H), 0.65 (2H), 2.19 (3H), 2.63 (2H), 2.79 (1H), 3 .54 (2H), 4.58 (2H), 543 (1H), 6.21 (1H), 7.06 (1H), 7.42 (1H), 7.47 (1H), 7.58- 7.70 (4H), 7.94 (1H), 8.24 (1H) ppt.

Example 393 4-(6-C4-chloro-2-(hydroxymethyl)phenyl|sulfanyl)-8-|(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)- M-cyclopropyl-2-methylbenzamide on on

Ve Shcho » he 8 Shcho he a he 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl) "M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using (5-chloro-2-sulfanylphenyl)methanol, obtaining after treatment and purification 57.0 mg (63 95) indicated in 1H-NMR (OM5O-46): b- 0.48 (2H), 0.65 (2H), 1.13 (6H), 2.19 (3H), 2.79 (1H), 3 ,24 (2H), 4.57 (2H), 4.72 (1H), 5.42 (1H), 6.28 (1H), 6-98 (1H), 7.06 (1H), 7, 41 (1H), 7.48 (1H), 7.59 (1H), 7.61 (1H), 7.64 (1H), 7.92 (1H), 8.23 (1H) ppt.

Example 394

M-cyclopropyl-4-76-((3-fluoro-5-methylphenyl)amino|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)u -2-methylbenzamide on on

Fo Fe vm / Ch8-x nim / r dh r oy oy 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazine -3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 3-fluoro-5-methylaniline, obtaining after treatment and purification 9.7 mg (11 95) of the title compound. 1H-NMR (0M5O-46): b- 0.49 (2H), 0.65 (2H), 1.18 (6H), 2.24 (3H), 2.34 (3H) , 2.81 (1H), 3.16 (2H), 4.81 (1H), 5.89 (1H), 6.52 (1H), 6.61 (1H), 7.05 (1H), 7.32 (1H), 7.53 (1H), 7.76 (1H), 7.88 (1H), 7.98 (1H), 8.29 (1H), 9.11 (1H) wt.

Example 395 4-(6-(2-aminophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazin-3-yl)y"-M-cyclopropyl-2-methylbenzamide and and

In U

MN MN

Fo Fe vm / sha om" /

НМ их r Охой ой 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)u)" M-Cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate Example 247a, was converted analogously to Example 51 using 2-aminophenol to give, after work-up and purification, 25.6 mg (32 95) of the title compound. 1H-NMR (0M50O -ab): b- 0.47 (2H), 0.63 (2H), 2.13 (ZH), 2.69 (2H), 2.76 (1H), 3.58 (2H), 4, 92 (2H), 6.08 (1H), 6.58 (1H), 6.79 (1H), 6.97 (1H), 7.03 (1), 7.13 (1H), 7.59 (1H), 7.67 (1H), 7.83 (1H), 7.91 (1H), 8.20 (1H) ppt.

Example 396 4-(6-(2-amino-4-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide (A) apa M-cyclopropyl-4-16-(4-fluoro-2-hydroxyphenyl)amino |-8-((3,3, 3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamide (B) more E E

In U U

MN MN MN

Fo Fo Fe vm / o om" / t nm zm nm but their ears blew: he y oy y oy

And in 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 2-amino-5-fluorophenol to give, after work-up and purification, 14.8 mg (18 95) of the title compound A apa 12.6 mg ( 15 95) of the title compound B. 1H-NMR (0M5O-46) of A: 6- 0.47 (2H), 0.64 (2H), 2.15 (3H), 2.69 (2H), 2.77 (1H), 3.58 (2H), 5.27 (2H), 6.08 (1H), 6.34 (1H), 6.55 (1H), 7.03 (1H), 7 .15 (1H), 7.60 (1H), 7.67 (1H), 7.83 (1H), 7.92 (IN), 8.22 (1H) ppt.

1H-NMR (0M5O-46) and B: 6b- 0.50 (2H), 0.66 (2H), 2.34 (ZH), 2.68 (2H), 2.81 (1H), 3, 49 (2H), 6.38 (1H), 6.55 (1H), 6.79 (1H), 7.26 (1H), 7.30 (1H), 7.76 (1H), 7.82 (1H), 8.04 (1H), 8.09 (1H), 8.14 (IN), 8.29 (1H), 9.86 (1H) ppt.

Example 397 4-(6-(2-chloro-3-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo

P,2-Shipyridazin-3-yl)y-N-cyclopropyl-2-methylbenzamidone

Pho Fe ve / -0- nim" / ve r; roy oy 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b |pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 2-chloro-3-fluoroaniline, obtaining after treatment and purification 6.0 mg (6 95) of the compound indicated in the title. 1H-NMR (0M5O-ab): b- 0.51 (2H), 0.66 (2H), 1.17 (6H), 2.36 (ZH), 2.81 (1H), 3.17 ( 2H), 4.83 (1), 5.95 (1H), 6.68 (1H), 7.28 (1H), 7.35 (1H), 7.40 (1H), 7.76 (1H ), 7.81 (1H), 7.95 (1H), 7.99 (1H), 8.91 (1H), 9.51 (1H) ppt.

Example 398

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino1|-6-|(3-methoxy-2-methylphenyl)amino|imidazo(1,2-b|Ipyridazin-3-yl- 2-methylbenzamide on on

Fo Fe ve / -0- nim" / uh ze uh oy oy 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b| pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305, using 3-methoxy-2-methylaniline, obtaining after treatment and purification 16.7 mg (20 95 ) of the title compound. 1H-NMR (0M50-ab): b- 0.48 (2H), 0.64 (2H), 1.18 (6H), 2.06 (ZH), 2.21 (ZH), 2.78 ( 1H), 3.15 (2H), 3.77 (ZH), 4.81 (1H), 5.97 (1H), 6.40 (1H), 6.73 (1H), 7.13 (1H ), 7.18 (1H), 7.24 (1H), 7.79 (2H), 8.01 (2H), 8.22 (1H) ppt.

Example 399

M-cyclopropyl-4-16-((2-hydroxyphenyl)amino|-8-(3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide

Ge) on

Fe Fe nm tm" / Ch-0 nm" / is r ve r oy oy

MG (76 μmol)

M-cyclopropyl-4-16-((2-methoxyphenyl)amino1|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridase n-3-yl/-2-methylbenzamide, which was obtained according to Example 388, was converted similarly

Intermediate Example 280, with treatment and purification yielding 14.7 mg (36 95) of the title compound.

1H-NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 2.35 (3H), 2.68 (2H), 2.80 (1H), 3.48 ( 2H), 6.28 (1H), 6.73-6.88 (ZH), 7.17 (1H), 7.30 (1H), 7.77 (1H), 7.83 (1H), 7.91 (1H), 8.10 (1H), 8.18 (1H), 8.28 (1H), 9.80 (1H) ppt.

Example 400

M-cyclopropyl-4-/6-((4-fluoro-3-methoxyphenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y- 2-methylbenzamide on on

Phew Phew

Ve zm / -- NM zm IY r toad one and one 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazine- 3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Intermediate Example 305, using 4-fluoro-33-methoxyaniline, obtaining after treatment and purification 20.3 mg (24 95) of the title compound. 1H-NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 1.18 (6H), 2.33 (3H), 2.81 (1H) , 3.16 (2H), 3.67 (ZH), 4.680 (1H), 5.85 (1H), 6.57 (1H), 7.08 (1H), 7.23 (1H), 7, 28 (1H), 7.33 (1H), 7.75 (1H), 7.86 (1H), 7.99 (1H), 8.27 (1H), 8.91 (1H) ppt.

Example 401 4-16-(4-chloro-3-fluorophenyl)amino|-8-(2-hydroxy-2-methylpropyl)amino]imidazo|(1,2-b|Ipyridazin-3-yl-"N-cyclopropyl- 2-methylbenzamide on on

Fe Fo

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazine -3-yl)"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Intermediate Example 305, using 4-chloro-3-fluoroaniline, obtaining after work-up and purification 5.6 mg (7 95 ) of the title compound. 1H-NMR (0M50O-ab): b- 0.52 (2H), 0.66 (2H), 1.18 (6H), 2.37 (3H), 2.82 (1H ), 3.17 (2H), 4.81 (IN), 5.91 (1H), 6.69 (1H), 7.28 (1H), 7.35 (1H), 7.41 (1) , 7.76 (1H), 7.81 (1H), 7.95 (1H), 7.99 (1H), 8.31 (1H), 9.41 (1H) ppt.

Example 402

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(2-methoxyphenyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2- methylbenzamide on on

Fo fe ve / nyu / o i i OV oi oi mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazine-3- il)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 2-methoxyaniline, obtaining after treatment and purification 59.7 mg (35 95) of the title compound.

1H-NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 1.18 (6H), 2.35 (ZH), 2.80 (1H), 3.17 ( 2H), 3.84 (ZH), 4.78 (1H), 6.29 (1H), 6.43 (1H), 6.88-6.96 (2H), 7.00 (1H), 7 .91 (1H), 7.77 (1H), 7.84 (1H), 7.92 (1H), 8.09 (1H), 8.25 (1H), 8.29 (1H) ppt.

Example 403

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-((3-methoxyphenyl) amino|imidazo|(1,2-b|pyridazin-3-yl)u.2 -methylbenzamide on on

Fe /F5

150 mg (327 μmol) 4-16-bromo-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|pyridazine -3-yl)"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305, using 3-methoxyaniline, to obtain, after work-up and purification, 44.4 mg (24 95) of the title compound 1H-NMR (0M5O-46): b- 0.51 (2H), 0.67 (2H), 1.18 (6H), 2.36 (3H), 2.81 (1H), 3.15 (2Н), 3.66 (ЗН), 4.80 (1Н), 5.88 (1Н), 6.48 (1Н), 6.55 (1Н), 7.16 (1Н), 7.20- 7.28 (2H), 7.32 (1H), 7.77 (1H), 7.86 (1H), 8.08 (1H), 8.29 (1H), 8.90 (1H) ppt.

Example 404 4-6-(5-chloro-2-methylphenyl)amino1-8-(2-hydroxy-2-methylpropyl)amino)imidazo|(1,2-b|Ipyridazin-3-yl-"M-cyclopropyl- 2-methylbenzamido on on /Fo /Fo

Ve zm / Ch-0-k NM zim / sho od: oi oi 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b |pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 5-chloro-2-methylaniline, obtaining after treatment and purification 6.2 mg (7 95) of the title compound. 1H-NMR (0M5O-46): b- 0.48 (2H), 0.64 (2H), 1.19 (6H), 2.23 (3H), 2.26 ( ЗН), 2.78 (1Н), 3.17 (2Н), 4.82 (1Н), 6.10 (1Н), 6.52 (1Н), 6.99 (1Н), 7.20 (1Н ), 7.26 (1H), 7.82 (1H), 7.88-7.96 (ZH), 8.01 (IN), 8.23 (1H) ppt.

Example 405 4-16-K2-chloro-4-fluorophenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y"-M-cyclopropyl- 2-methylbenzamidon on ve / -0-k nim" / si r r o r oy y on

Zo 75 mg (164 μmol) 4-/6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-B|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide , which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 2-chloro-4-fluoroaniline to give after treatment and purification 7.3 mg (8 95) of the title compound.

1H-NMR (0M50O-ab): b- 0.49 (2H), 0.64 (2H), 1.18 (6H), 2.24 (ZH), 2.78 (1H), 3.17 ( 2H), 4.80 (1), 5.72 (1H), 6.09 (1H), 6.53 (1H), 7.23 (1H), 7.49 (1H), 7.76 (1H ), 7.79 (1H), 7.90 (1H), 7.92 (1H), 8.23 (1H), 8.25 (1H) ppt.

Example 406

M-cyclopropyl-4-16-|(b-fluoropyridin-3-yl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1, 2-B|Ipyridazin-3-yl-g-methylbenzamide he he so s

Ve zm / -U-8U-5Zk NM z / i MA zymon y on 50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2 -b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using b-fluoropyridin-3-amine, obtaining after treatment and purification 9.9 mg (18 95) of the title compound. 1H-NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 1.18 (6H), 2.37 (3H), 2, 81 (1H), 3.17 (2H), 4.80 (1H), 5.687 (1H), 6.67 (1H), 7.10 (1H), 7.34 (1H), 7.76 (1H ), 7.78 (1H), 8.00 (1H), 8.16 (1H), 8.29 (1H), 8.50 (1H), 9.17 (1H) ppt.

Example 407 4-(6--(cyclopentylamino)-8-((2-hydroxy-2-methylpropyl)amino|imidazo1,2-BI pyridazin-3-yl)y"-M-cyclopropyl-2-methylbenzamidone and

Fo Fe vm / 5-5 nim / v, o p» oi oi 50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b |pyridazin-3-yl)"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305, using cyclopentanamine to obtain after treatment and purification 10.8 mg (20 95) of the title compound. 1H-NMR (0M50-ab): 0-0.50 (2H), 0.64 (2H), 1.15 (6H), 1.43-1.72 (6H), 1.97 (2H), 2.34 (ZH), 2.79 (1H), 3.06 (2H), 3.99 (1H), 4.76 (1H), 5.61 (1H), 6.17 (1H), 6 .37 (1H), 7.29 (1H), 7.72 (1H), 7.99 (1H), 8.17 (1H), 8.24 (1H) ppt.

Example 408 4-(6-(cyclopent-3-en-1-ylamino)-8-K(2-hydroxy-2-methylpropyl)amino|imidazo

P,2-Shipyridazin-3-yl)u-M-cyclopropyl-2-methylbenzamidon ve / -05-k nimi" / r o r o oy 100 mg (218 μmol) 4-(6-bromo-8- K(2-hydroxy-2-methylpropyl)amino|midazo(1,2-5|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted similarly to Example 305 using cyclopent -3-en-1-amine, with treatment and purification yielding 12.8 mg (12 95) of the title compound.

1H-NMR (0M50-a6): 6b- 0.50 (2H), 0.64 (2H), 1.15 (6H), 2.25 (1H), 2.28 (1H), 2.34 ( ЗН), 2.73-2.83 (ЗН), 3.07 (2Н), 4.32 (1Н), 4.76 (1Н), 5.61 (1Н), 5.73 (2Н), 6 .21 (1H), 6.57 (1H), 7.931 (1H), 7.73 (1H), 8.02 (1H), 8.13 (1H), 8.25 (1H) ppt.

Example 409

M-cyclopropyl-4-[6-((3-ethenylphenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamide he he

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1 ,2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 3-vinylaniline, obtaining after work-up and purification 28.0 mg (33 95) of the compound indicated in the title. 1H-NMR (0M50O-ab): b- 0.51 (2H), 0.66 (2H), 1.18 (6H), 2.34 (ZH), 2.81 (1H), 3.16 ( 2H), 4.81 (1H), 5.18 (1H), 5.67 (1H), 5.89 (1H), 6.56 (1H), 6.64 (1H), 7.03 (1H ), 7.24 (1H), 7.91 (1H), 7.62 (1H), 7.63 (1H), 7.77 (1H), 7.91 (1H), 8.01 (1H) , 8.29 (1H), 8.94 (1H) ppt.

Example 410

M-cyclopropyl-4-76-((b-fluoropyridin-3-yl)oxy|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u .2-methylbenzamide on on

Fe Fo vm / -0ЬО520О--k ob / vo

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)" M-Cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate Example 9ba, was converted analogously to Example 51 using b-fluoropyridin-3-ol to give, after work-up and purification, 4.1 mg (5 95) of the title compound. 1H - NMR (0M50-ab): b- 0.47 (2Н), 0.64 (2Н), 1.17 (6Н), 2.14 (ЗН), 2.77 (1Н), 3.28 (2Н ), 4.75 (1H), 6.24 (1H), 7.07 (1H), 7.17 (1H), 7.32 (1H), 7.61 (1), 7.68 (1H) , 7.92 (1H), 8.03 (1H), 8.23 (1H),

Yu (825(1H) ppt.

Example 411 5-((3-(4-(cyclopropylcarbamoyl)-3-methylphenyl/|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-6b-yloxy)nicotinamidone one

Fo Fo vm / pk om / r be r

NMU ik, M on o o y 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)" M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 5-hydroxynicotinamide to give, after work-up and purification, 22.0 mg (25 95) of the title compound.

1H-NMR (0M5O-46): b- 0.46 (2H), 0.63 (2H), 1.17 (6H), 2.09 (ZH), 2.76 (1H), 3.13 ( 2H), 4.75 (1), 6.27 (1H), 7.10 (1H), 7.13 (1H), 7.61 (1H), 7.64 (1H), 7.69 (1H ), 7.92 (1H), 8.17-68.22 (ZH), 8.72 (1H), 8.96 (1H) ppt.

Example 412

M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino|-6-(pyrazin-2-ylsulfanyl) imidazo|1,2-b|Ipyridazin-3-yl-g-methylbenzamidone one

Fo /Fe ve" / 0-0 vm" / r lya uh o y oi 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo(1,2 -β|pyridazin-3-yl)"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using pyrazine-2-thiol, obtaining after treatment and purification 17.5 mg (21 95) of the title compound. 1H-NMR (0M5O-46): b- 0.49 (2H), 0.65 (2H), 1.13 (6H), 2.23 (3H), 2.79 ( 1H), 3.25 (2H), 4.71 (1H), 6.48 (1H), 7.16 (1H), 7.19 (1H), 7.66 (1H), 7.71 (1H ), 7.97 (1H), 8.25 (1H), 8.58 (1H), 8.61 (1H), 8.83 (1H) ppt.

Example 413

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(4-methyl-4H-1,2,4-triazol-3-yl)usulfaniliimidazo|1,2-b |pyridazin-3-yl)u.2-methylbenzamid on on du 00.00

Ve zm / 5 zm / r Med - Moi 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazine-3 - yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51, using 4-methyl-4H-1,2,4-triazole-3-thiol, to obtain after treatment and purification 17.5 mg (21 95) of the title compound 1H-NMR (OM5O-ab): b- 0.51 (2H), 0.66 (2H), 1.14 (6H), 2.28 (3 ), 2.80 (1Н), 3.25 (2Н), 3.61 (ЗН), 4.73 (1Н), 6.38 (1Н), 7.17 (1Н), 7.21 (1Н) , 7.48 (1H), 7.60 (1H), 7.96 (1H), 8.28 (1H), 8.93 (1H) ppt.

Example 414

M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino|-6-(1H-pyrazol-5-yloxy)imidazo|1,2-b|Ipyridazin-3-yl-g-methylbenzamide he he

Fo Fo vesm' y / CHU-k om" / r Ov me o o o 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2- b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 1H-pyrazol-5-ol, obtaining after treatment and purification 5.5 mg ( 7 95) of the compound indicated in the title.

1H-NMR (0M5O-46): b- 0.48 (2H), 0.64 (2H), 1.15 (6H), 2.25 (ZH), 2.78 (1H), 3.26 ( 2H), 4.75 (1H), 6.13 (1H), 6.16 (1H), 6.98 (1H), 7.23 (1H), 7.73-7.80 (2H), 7 .91 (1H), 7.93 (1H), 8.26 (1H), 12.45 (1H) ppt.

Example 415

M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino1|-6-(5-methyl-1H-pyrazol-3-yl)oxy|imidazo|1,2-b|Ipyridazine-3 -ylu-2-methylbenzamidon on on to sx vm / 0-x om" /

M y r "ad o y o y 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)" M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51 using 5-methyl-1H-pyrazol-3-ol, obtaining after treatment and purification 6.3 mg (8 95) indicated in the title of the compound. 1H-NMR (0M5O-46): b- 0.48 (2H), 0.64 (2H), 1.15 (6H), 2.23 (ZH), 2.26 (ZH), 2.79 ( 1H), 3.26 (2H), 4.74 (1H), 5.92 (1H), 6.11 (1H), 6.96 (1H), 7.24 (1H), 7.77 (1H ), 7.90 (1H), 7.96 (1H), 8.26 (1H), 12.13 (1H) ppt.

Example 416 4-16-(cyclohexylamino)-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-BI pyridazin-3-yl)y-M-cyclopropyl-2-methylbenzamidone

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b |pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305, using cyclohexanamine, to obtain after treatment and purification 7.8 mg (10 95) of the title compound . 1H-NMR (0M5O-ab): 0-0.50 (2H), 0.64 (2H), 1.11-1.42 (5H), 1.15 (6H), 1.60 (1H), 1.73 (2H), 2.03 (2H), 2.35 (ZH), 2.79 (1H), 3.06 (2H), 3.56 (1H), 4.77 (1H), 5 .61 (1H), 6.17 (1H), 6.25 (1H), 7.28 (1), 7.72 (1H), 7.95(1H), 8.16 (1H), 8, 26 (1H) ppt.

Example 417 4-16-K2-amino-4-fluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y"-M-cyclopropyl -2-methylbenzamide pi c

In U

MN MN

Fo Fe ve / - vm /

N.M ikh r oo on and on

From 75 mg (156 μmol) of 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-B|Ipyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide) , which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 2-amino-4-fluorobenzenethiol to give after work-up and purification 23.7 mg (27 95) of the title compound.

1H-NMR (0M5O-46): b- 0.48 (2H), 0.65 (2H), 2.24 (3H), 2.60 (2H), 2.79 (1H), 3.49 ( 2H), 5.75 (2H), 6.02 (1H), 6.40 (1H), 6.58 (1H), 7.12 (1H), 7.38 (1H), 7.60 (1H ), 7.74 (1H), 7.75 (1H), 7.93 (1H), 8.24 (1H) ppt.

Example 418

M-cyclopropyl-4-/6-(2-methoxy-3-(propane-2-ylphenoxy|-8-(3,3,3- trifluoropropyl)amino|imidazo|(1,2-b|pyridazine-3- il)u.2-methylbenzamide p pi

In R

MN MN

DU - DK

Ve zm / | c) zm / (v u TO B, o n o n 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b| Ipyridazin-3-yl)u"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 3-isopropyl-2-methoxyphenol, obtaining after treatment and purification 45 mg (48 95) of the title compound. 1H-NMR (0M50-46): b- 0.45 (2H), 0.63 (2H), 1.16 (6H), 2.06 (3H), 2.60-2, 80 (ZH), 3.17-3.26 (1), 3.60 (2H), 3.71 (ZH), 6.17 (1H), 7.04-7.23 (4H), 7, 61 (1H), 7.67 (1H), 7.71 (1H), 7.94 (1H), 8.19 (1H) ppt.

Example 419

M-cyclopropyl-2-methyl-4-16-(4-methyl-4H-1,2,4-triazol-3-yl)usulfanyl|-8-

I(3,3,3-trifluoropropyl)amino|imidazo(/1,2-b|Ipyridazine-3-ylbenzamide

She in

In U

MN MN

UV /Fe vm" / sho v" / r ke shadh - My oy 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51, using 4-methyl-4H-1,2,4-triazole-3-thiol, with obtaining after treatment and purification 29.4 mg (35 95) of the title compound. 2.66 (2H), 2.80 (1H), 3.57 (2H), 3.61 (ZH), 6.35 (1H), 7.20 (1H), 7.46 (1H), 7 .59 (1H), 7.84 (1H), 7.96 (1H), 8.27 (1H), 8.93 (1H) ppt.

Example 420

M-cyclopropyl-2-methyl-4-16-(pyrazin-2-ylsulfanyl)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)ibenzamide pi AND

In U

MN MN

WHO - WHERE

Ve zm i v zi Y uh Ov

My 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)"M-cyclopropyl- 2-Methylbenzamide, which was prepared according to Intermediate Example 247a, was converted analogously to Example 51 using pyrazine-2-thiol to give, after work-up and purification, 28.6 mg (34 95) of the title compound. 1H-NMR (0M5O-46 ): b- 0.49 (2Н), 0.64 (2Н), 2.23 (ЗН), 2.64 (2Н), 2.79 (1Н), 3.57 (2Н), 6.43 ( 1H), 7.18 (1H), 7.64 (1H), 7.69 (1H), 7.83 (1H), 7.97 (1H), 8.25 (1H), 8.57-8 .62 (2H), 8.86 (1H) ppt.

Example 421

M-cyclopropyl-4-(6-Z(185,285)-2-hydroxycyclohexyl|oxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|pyridazin-3-yl )-2-methylbenzamid on on /Fo Pho

50 mg (109 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b| pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 51, using (1K5, 2K5)-cyclohexane-1,2-diol, obtaining after treatment and purification 2 .8 mg (5 95) of the title compound. 1H-NMR (0M50-ab): 0- 0.50 (2H), 0.65 (2H), 1.13 (6H), 1.23-1, 39 (4H), 1.66 (2H), 1.89 (1H), 102.36 (ZH), 2.80 (1H), 3.19 (2H), 3.54 (1H), 4.65 (1H), 4.72 (1H), 4.82 (1H), 5.72 (1H), 5.84 (1H), 6.66 (1H), 7.33 (1H), 7.687 (1H ), 7.91 (1H), 8.08 (1H), 8.29 (1H) ppt.

Example 422

M-cyclopropyl-4-76-((4-fluoro-3-methoxyphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl) u.2-methylbenzamide and EI

In U

MN MN

/Fe /Fe

100 mg (207 μmol) 4-(6-bromo-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-5|pyridazine -3-yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using 4-fluoro-3-methoxyaniline, obtaining after treatment and purification 43.1 mg (38 95 ) of the title compound. 1H-NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 2.33 (3H), 2.67 (2H), 2.81 (1H ), 3.49 (2H), 3.67 (ZH), 5.78 (1H), 7.08 (1H), 7.19-7.37 (4H), 7.76 (1H), 7, 85 (1H), 7.99 (1H), 8.27 (1H), 8.94 (1H) ppt.

Example 423

M-cyclopropyl-2-methyl-4-(6-(3-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl) Ibenzamide and i

In U

MN MN

/Fe /Fo

Ve zm / o- nyu zm /

75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazine-3- yl)y"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305 using m-toluidine, obtaining after treatment and purification 14.5 mg (17 95) of the title compound. 1H - NMR (SOSIS): b- 0.63 (2H), 0.90 (2H), 2.35 (ЗН), 2.43-2.58 (2Н), 2.51 (ЗН), 2.61 (1H), 2.92 (1), 3.59 (2H), 5.64 (1H), 5.78 (1H), 5.91 (1H), 6.25 (1H), 6.89 ( 1H), 7.22 (1H), 7.35 (1H), 7.40 (1H), 7.65 (1H), 7.90 (1H), 7.92 (1H) ppt.

Example 424

M-cyclopropyl-4-/6-|(3-fluoro-4-methoxyphenyl)amino|-8-((3,3,3-

trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2-methylbenzamide and and

In U

MN MN

DU 0-0 KO

Ve zm / nyu zm / r oo dh on 79 on 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazine- 3-yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using 3-fluoro-4-methoxyaniline, to obtain after treatment and purification 21.0 mg (24 95) of the title compound. 1H-NMR (SOSIS): b- 0.64 (2H), 0.90 (2H), 2.44-2.60 (2H), 2.51 (3H), 2.92 ( 1H), 3.59 (2H), 3.89 (ZH), 5.55 (1H), 5.78 (1H), 5.94 (1H), 6.20 (1H), 6.92 (1H ), 7.06 (1H), 7.41 (1H), 7.55 (1H), 7.64 (1H), 7.83 (1H), 7.92 (1H) ppt.

Example 425

M-cyclopropyl-4-16-((4-methoxyphenyl)amino1|-8-(3,3,3-trifluoropropyl)amino imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide and and

In U

MN MN

)Fe /Fo

Ve zm / o- nyu zm /

I I (FA o J times, He! J 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-B|Ipyridazine-3- yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using 4-methoxyaniline, with obtaining after work-up and purification 17.8 mg (21 95) of the title compound. 1H- NMR (SOSIZ): b- 0.63 (2Н), 0.90 (2Н), 2.43-2.60 (2Н), 2.51 (ЗН), 2.92 (1Н), 3.57 ( 2H), 3.82 (ZH), 5.56 (1H), 5.77 (1H), 5.91 (1H), 6.10 (1H), 6.91 (2H), 7.35-7 .42 (ZH), 7.64 (1H), 7.83 (1H), 7.98 (IN) ppt.

Example 426

M-cyclopropyl-4-16-((3-methoxy-2-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl) u.2-methylbenzamide and EI

In R

МН МН s s ve / - nim" / uhve uhoy oy 150 mg (311 μmol) 4-(6-bromo-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-5|pyridazine -3-yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using 3-methoxy-2-methylaniline, obtaining after treatment and purification 21.3 mg (12 95 ) of the title compound. 1H-NMR (SOSIS): b- 0.62 (2H), 0.89 (2H), 2.20 (ЗН), 2.47 (ЗН), 2.50 (2Н), 2.92 (1Н) , 3.55 (2H), 3.87 (ZH), 5.63 (1H), 5.81 (1H), 5.89 (1H), 6.00 (1H), 6.72 (1H), 7.16-7.25 (2H), 7.36 (1H), 7.65 (1H), 7.84 (1H); 7.93 (1H) ppt.

Example 427

M-cyclopropyl-4-(6-(C4-(2-hydroxyethyl)phenyl|amino)-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl )-2-methylbenzamide

IS

E E sa U

MN MN ko o z. --e2 threads

Ve M r

Yeh o o n Fn 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl))"M -cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using 2-(4-aminophenyl)ethanol, to obtain after work-up and purification 9.2 mg (10 95) of the title compound. 1H -NMR (0М50-46): b- 0.52 (2Н), 0.66 (2Н), 2.38 (ЗН), 2.58-2.77 (4Н), 2.82 (1Н), 3 ,41-3.59 (4H), 4.59 (1H), 5.682 (1H), 7.11 (2H), 7.24 (1H), 7.34 (1H), 7.56 (2H), 7.77 (1H), 7.83 (1H), 8.12 (1H), 8.32 (1H), 8.86 (1H) ppt.

Example 428

M-cyclopropyl-4-76-((4-fluoro-3-methylphenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u .2-methylbenzamide and and

In U

MN MN

Fo Fe vm" / shiya nim" / ih r ore: oi and oi 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2- b|Ipyridazin-3-yl)u"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using 4-fluoro-3-methylaniline, to obtain after treatment and purification 11.9 mg (14 95) of the compound indicated in the title. 1H-NMR (SOSIS): b- 0.63 (2H), 0.89 (2H), 2.25 (3H), 2.42-2.56 (2H), 2.48 (ZH), 2.92 (1H), 3.53 (2H), 5.57 (1H), 5.87 (1H), 5.99 (1H), 6.39 (1H), 6 .95 (1H), 7.21-7.34 (2H), 7.36 (1H), 7.62 (1H), 7.85 (1H), 7.87 (1H) ppt.

Example 429

M-cyclopropyl-4-16-((b-methoxypyridin-3-yl)amino1|-8-((3,9,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl) y.2-methylbenzamide EI

In U

MN MN about: more;

75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo|1) 2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using b-methoxypyridin-3-amine, to obtain after treatment and purification 8.7 mg (10 95) of the title compound. 1H-NMR (0M5O-46): b- 0.50 (2H), 0.64 (2H), 2.37 (3H), 2.68 (2H), 2 .80 (1H), 3.30 (ZH), 3.49 (2H), 5.77 (1H), 6.78 (1H), 7.25-7.35 (2H), 7.77 (2H ), 7.93 (1H), 8.09 (1H), 8.29 (1H), 8.46 (1H), 8.86

Z0 (IN) ppt.

Example 430

M-cyclopropyl-4-16-(5-methoxy-2-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u .2-methylbenzamide and EI

In U

MN MN

DU 0-0 DK

150 mg (311 μmol) 4-(6-bromo-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-5|pyridazin-3-yl) )"M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305 using 5-methoxy-2-methylaniline, obtaining after work-up and purification 15.5 mg (9 95) of the title compound 1H-NMR (SOSIS): b- 0.62 (2H), 0.89 (2H), 2.26 (ЗН), 2.48 (ЗН), 2.52 (2Н), 2.92 (1Н ), 3.58 (2H), 3.73 (ZH), 5.65 (1H), 5.79 (1H), 5.89 (1H), 5.96 (1H), 6.62 (1H) , 7.14 (1H), 7.31 (1H), 7.38 (1H), 7.66 (1H), 7.87 (1H), 7.90 (1H) ppt.

Example 431

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(2-hydroxyphenyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2- methylbenzamide on on

Phew Phew

Nm zm / -090--k nim / "С шо их ррой ой 40 MG (80 μmol)

M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(2-methoxyphenyl)amino|imidazo(|1,2-5|pyridazin-3-yl)-2- methylbenzamide, which was obtained according to Example 402, was converted analogously to Example 280 to obtain, after treatment and purification, 5.8 mg (13 95) of the title compound. 1H-NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 1.17 (6H), 2.36 (ZH), 2.81 (1H), 3.17 (2H), 4.76 (1H), 6.28 (1H), 6 .40 (1H), 6.71-6.89 (ZH), 7.30 (1H), 7.76 (1H), 7.80-7.91 (2H), 8.11 (1H), 8 .16 (1H), 8.29 (1H), 9.90 (1H) ppt.

Example 432

M-cyclopropyl-4-/6-((4-fluoro-2-methoxyphenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y- 2-methylbenzamide on on

Fo Fe ve / -0-k | Nm zm / (in it 150 mg (327 μmol) 4-(6-bromo-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2-b|Ipyridazin-3- il)"M-Cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 4-fluoro-2-methoxyaniline to give, after work-up and purification, 12.2 mg (6 95) of the title compound 1H-NMR (0M5O-46): b- 0.51 (2H), 0.65 (2H), 1.18 (6H), 2.32 (3H), 2.80 (1H), 3, 15 (2Н), 3.84 (ЗН), 4.79 (1Н), 6.21 (1Н), 6.42 (1Н), 6.72 (1Н), 6.96 (1Н), 7.30 (1H), 7.76 (1H), 7.82 (1H), 7.91 (1H), 8.01 (1), 8.10 (1H), 8.27 (1H) ppt.

Example 433

M-cyclopropyl-2-methyl-4-(6-(3-(propan-2-yl)uphenyl|amino)-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b |pyridazin-3-yl)benzamide and i

In U

MN MN

Ve zm / nyu zm / oy | 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)y"N-cyclopropyl-2 -methylbenzamide, which was prepared according to Intermediate Example 247a, was converted analogously to Example 305 using 3-isopropylaniline to give, after workup and purification, 22.8 mg (26 95) of the title compound.1H-NMR (0M50-ab): 0 - 0.50 (2H), 0.66 (2H), 1.16 (6H), 2.37 (ZH), 2.49-2.88 (4H), 3.49 (2H), 5.84 (1H), 6.79 (1H), 7.19 (1H), 7.23-7.29 (2H), 7.33 (1H), 7.70 (1H), 7.77 (1H), 7.92 (1H), 8.02 (1H), 8.29(1H), 8.88 (1H) ppt.

Example 434

M-cyclopropyl-4-(6-C2-(hydroxymethyl)phenyl|amino)-8-((2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|pyridazin-3-yl)-2- methylbenzamide on on

75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl) "M-Cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using (2-aminophenyl)methanol to give, after work-up and purification, 2.0 mg (2 95) of the title compound. 1H - NMR (0М5О-46): b- 0.49 (2Н), 0.64 (2Н), 1.18 (6Н), 2.26 (ЗН), 2.78 (1Н), 3.18 (2Н ), 4.54 (2H), 4.80 (1H), 5.35 (1H), 5.96 (1H), 6.46 (1H), 7.03 (1H), 7.24 (2H) , 7.36 (1Н), 7.77-7.91 (НН), 8.02 (1Н), 8.06 (1Н), 8.24 (1Н) ppt.

Example 435 4-(6-P4-(2-aminoethyl)phenyl|amino)-8-(2-hydroxy-2-methylpropyl)amino imidazo|1,2-b|pyridazin-3-yl)-M-cyclopropyl- 2-methylbenzamidon vetcha

MN M se sia se /Fi y z MM ---z NM

Vi M ikh r y u

M o nn o nn mn, 75 mg (164 μmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M -cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 9ba, was converted analogously to Example 305 using 4-(2-aminoethyl)aniline to give, after work-up and purification, 11 mg (12 95) of the title compound.1H-NMR (0М50-46): b- 0.51 (2Н), 0.66 (2Н), 1.18 (6Н), 2.38 (ЗН), 2.59-2.65 (2Н), 2.74 -2.85 (ЗН), 3.15 (2Н), 4.82 (1Н), 5.88 (1Н), 6.51 (1), 7.10 (2Н), 7.34 (1Н), 7.58 (2H), 7.76 (1H), 7.84 (1H), z 8.12 (1H), 8.32 (1H), 8.87 (1H) mp.

Example 436

M-cyclopropyl-4-[6-|(b-fluoropyridin-3-yl)oxy1|-8-((3,3,3-trifluoropropyl)amino]imidazo|1,2-b|Ipyridazin-3-yl)u -2-methylbenzamide and i

In U

MN MN

Fe ee DK vm / om" / o r sha. oi y on 200 mg (415 μmol) 4-(6-bromo-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-5|pyridazine -3-yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using b-fluoropyridin-3-ol, obtaining after work-up and purification 4.8 mg (2 95 ) of the title compound. 1H-NMR (0M50-avb): 0-0.47 (2H), 0.64 (2H), 2.13 (ZH), 2.60-2.80 (ZH), 3.61 (2H), 6.19 (1H), 7.17 (1H), 7.32 (1H), 7.60 (1H), 7.67 (1H), 7.77 (1H), 7.93 (1H), 8 .04 (1H), 8.22 (1H), 8.26 (1H) ppt.

Example 437

M-cyclopropyl-4-76-(2-fluoro-4-methoxyphenoxy)-8-I((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y). 2-methylbenzamide and EI

In U

MN MN

ДУОо- ДК вм / оз / р рова о Y -9 Ge! And 400 mg (829 μmol) 4-16-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide , which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 2-fluoro-4-methoxyphenol to give, after work-up and purification, 194 mg (41 95) of the title compound.1H-NMR (0M50-ab): 0 - 0.46 (2H), 0.64 (2H), 2.08 (ZN), 2.60-2.80 (ZN), 3.60 (2H), 3.78 (ZN), 6.16 (1H), 6.84 (1H), 7.06 (1H), 7.15 (1H), 7.33 (1H), 7.61 (1H), 7.67-7.74 (2H), 7.94 (1H), 8.21 (1H) ppt.

Example 438

M-cyclopropyl-4-76-(2-fluoro-4-methoxyphenoxy)-8-I((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)ibenzamid and

In U

MN MN

DU - DK vm / o7zm / uh yuyu Ov o N ra Go! M 400 mg (854 μmol) of 4-/6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)"M-cyclopropylbenzamide, which was obtained according to Intermediate Example 438a, was converted analogously to Example 51 using 2-fluoro-4-methoxyphenol to give after work-up and purification 219 mg (46 95) of the title compound.1H-NMR (0M5O-46): 6-0, 53 (2H), 0.66 (2H), 2.69 (2H), 2.79 (1H), 3.60 (2H), 3.81 (ZH), 6.17 (1H), 6.85 (1H), 7.08 (1H), 7.34 (1H), 7.65 (2H), 7.74 (1H), 7.89 (2H), 8.01 (1H), 8.40 ( 1H) ppt.

Intermediate Example 43va 4-16-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)y-M-cyclopropylbenzamide vec RU

In MN o M ky - u/Fe Ve M

Weigh 1.50 g (3.45 mmol) of 6-bromo-3-iodo-M-(3,3,3-trifluoropropyl)imidazo(1,2-B|Ipyridazine-8-amine, which was obtained according to with Intermediate Example 2470, converted similarly to Intermediate

Example 1a, using I4-(cyclopropylcarbamoyl)phenyl|boronic acid, obtaining after treatment and purification 1.05 g (65 95) of the title compound.

Example 439

M-cyclopropyl-2-methyl-4-16-(pyridin-3-ylamino)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)ibenzamide and She

In U

MN MN

Fo Fe vm / -o- nm" / p

M

? h o n o n 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl)u"M -cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate Example 247a, was converted analogously to Example 305 using pyridine-3-amine to give, after work-up and purification, 15.5 mg (1995) of the title compound. 1H-NMR ( 0М5О-46): b- 0.51 (2Н), 0.66 (2Н), 2.38 (ЗН), 2.68 (2Н), 2.81 (1Н), 3.51 (2Н), 5 .84 (1), 7.29 (1H), 7.34 (1H), 7.38 (1H), 7.79 (1H), 7.80 (1H), 8.06 (1H), 8, 10-8.16 (2H), 8.32 (1H), 8.80 (1H), 9.18 (1H) ppt.

Example 440

M-cyclopropyl-4-16-|(b-fluoropyridin-3-yl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u .2-methylbenzamide

In U

MN MN

DOCK

Ve zm in Nm zi Y

F

M g E h o n o n n 75 mg (156 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2-b|Ipyridazin-3-yl) y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 305, using b-fluoropyridin-3-amine, to obtain after work-up and purification 25.5 mg (30 95) of the title compound 1H-NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 2.37 (3H), 2.68 (2H), 2.81 (1H), 3.50 (2H), 5.80 (1), 7.12 (1H), 7.34 (1H), 7.39 (1H), 7.76-7.80 (2H), 8.00 (1H), 8.16 (1H), 8.91 (1H), 8.51 (1H), 9.21 (IN) ppt.

Example 441

M-cyclopropyl-4-/6-(2-hydroxy-3-(propane-2-ylphenoxy|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazine-3 -yl)u.2-methylbenzamide and EI

In U

MN MN

SYU 0-0 o zm Y o zi Y

Bezo oy oy 32 MG (56 μmol)

M-cyclopropyl-4-16-(2-methoxy-3-(propane-2-ylphenoxy)|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-B|Ipyridazin-3-yl -2-methylbenzamide, which was obtained according to Example 418, was converted analogously to Example 280 to obtain, after treatment and purification, 8.2 mg (25 95) of the title compound. 1H-NMR (0M50-ab): b- 0.46 ( 2H), 0.62 (2H), 1.07 (6H), 2.05 (ZH), 2.69 (2H), 2.75 (1H), 3.04 (IN), 3.60 (2H ), 6.14 (1H), 6.76 (1H), 6.82 (1H), 7.03-7.09 (2H), 7.56 (1H), 7.62 (1H), 7, 77 (1H), 7.93 (1H), 8.19 (1H), 9.37 (1H) ppt.

Example 442

M-cyclopropyl-4-16-|((4-fluoro-3-hydroxyphenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl) u.2-methylbenzamide

EI EI

In U

MN MN

Fe Fe nem" / o- nm m" / be r What. r y on y on 33 MG (61 μmol) M-cyclopropyl-4-(6-(4-fluoro-

3-Methoxyphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, which was obtained according to Example 422, was converted similarly

of Example 280 with obtaining after processing and purification 9.3 mg (27 95) of the title compound. 1H-NMR (0M5O-46): b- 0.51 (2H), 0.66 (2H), 2.36 (3H), 2.67 (2H), 2.81 (1H), 3.47 ( 2H), 5.78 (1H), 7.00 (1H), 7.05 (1H), 7.20-7.27 (2H), 7.33 (1H), 7.78 (1H), 7 .87 (1H), 8.06 (1H), 8.28 (1H), 8.79 (1H), 9.71 (1H) ppt.

Example 443

M-cyclopropyl-4-16-|((5-hydroxy-2-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl )u.2-methylbenzamide

And I

In U

MN MN

SYU - DK ni zm / nyu zm / b» In o) her 6) her 10.5 MG (19 μmol)

M-cyclopropyl-4-16-((5-methoxy-2-methylphenyl)amino1|-8-((3,3,3-trifluoropropyl)amino|imidazoi|1,2-B pyridazin-3-yl/-2 -methylbenzamide, which was obtained according to Example 430, was converted similarly to Example 280, obtaining after treatment and purification 2.0 mg (20 95) of the title compound. 1H-NMR (0M5O-46): 6- 0.47 (2H ), 0.64 (2H), 2.11 (ЗН), 2.24 (ЗН), 2.69 (2Н), 2.77 (1Н), 3.48 (2Н), 5.94 (1Н) , 6.42 (1H), 6.95 (1H), 7.10 (1H), 7.16 (1H), 7.20 (1H), 7.65-7.95 (ЗН), 8.01 (1H), 8.21 (1H), 9.06 (1H) ppt.

Example 444

M-cyclopropyl-4-16-(2-fluoro-4-methoxyphenoxy)-8-|((tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl) Ibenzamide (in) (in t, t,

Fe / Fo --

Ve zm / (o) zm /

IS

6) 400 MG (850 μmol) 4-(6-bromo-8-(tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo

P,2-5-Ipyridazin-3-yl)y-N-cyclopropylbenzamide, which was obtained according to Intermediate Example 444a, was converted analogously to Example 51 using 2-fluoro-4-methoxyphenol, obtaining after treatment and purification 257 mg (54 95) of the title compound. 1H-NMR (0M50-a6): b- 0.53 (2H), 0.66 (2H), 1.22 (2H), 1.62 (2H), 1.94 (1H), 2.80 ( 1H), 3.17-3.32 (AN), 3.81 (ZN), 3.84 (2H), 6.12 (1H), 6.84 (1H), 7.07 (1H), 7 .34 (1H), 7.64 (2H), 7.74 (1H), 107.89 (2H), 7.98 (1H), 8.39 (1H) ppt.

Intermediate Example 444a 4-6-bromo-8-Ktetrahydro-2H-pyran-4-ylmethyl)amino|imidazo(1,2-5I|Ipyridazin-3-yl)"M-cyclopropylbenzamide (c) more MH

MN --- se

CHI, u/Fe Vg M

FU -

Ve M! 5 years:

Mo nn 1.20 g (2.75 mmol) of 6-bromo-3-iodo-M-(tetrahydro-2H-pyran-4-ylmethyl)imidazo|1,2-BI pyridazine-8-amine, which was obtained according to with Intermediate Example 444p, was converted similarly to Intermediate Example a, using (|4-(cyclopropylcarbamoyl)phenyl boronic acid, obtaining after processing and purification 1.08 g (84 95) of the title compound.

Intermediate Example 444b-bromo-3-iodo-M-(tetrahydro-2H-pyran-4-ylmethyl)imidazo(1,2-b|Ipyridazin-8-amine (c)

Ve shchi /Fe - MN

Fe; vm / Fe

AND

Ve with

AND

3.00 g (7.45 mmol) of 6,8-dibromo-3-iodoimidazo|(1,2-b|Ipyridazine, which was obtained according to

Intermediate Example 9bs was converted similarly to Intermediate Example 16, using 1-(tetrahydro-2H-pyran-4-yl)umethanamine, to obtain after treatment and purification 2.81 g (81 95) of the title compound.

Example 445

M-cyclopropyl-4-(6-(2-fluoro-4-methoxyphenoxy)-8-((tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo|1,2-b|pyridazin-3-yl)u .2-methylbenzamide o o

MN MN

/Fo /Fo -»

Ve zm / c) zm /

E o i yo o Y 400 MG (826 μmol) 4-(6-bromo-8-(tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 445a was converted analogously to Example 51, using 2-fluoro-4-methoxyphenol, to obtain after treatment and purification 295 mg (65 95) of the title compound. 1H-NMR (0M5O-46): b- 0.46 (2H), 0.63 (2H), 1.22 (2H), 1.62 (2H), 1.95 (1H), 2.08 ( ЗН), 2.77 (1), 3.19-3.27 (4Н), 3.77 (ЗН), 3.83 (2Н), 6.12 (1Н), 6.83 (1Н), 7 .05 (1H), 7.14 (1H), 7.33 (1H), 7.61 (1), 7.67-7.74 (2H), 7.91 (1H), 8.21 (1H ) ppm

Intermediate Example 445a 4-(6-bromo-8-|((tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo(1,2-b|pyridazine-

3-yl)"M-cyclopropyl-2-methylbenzamide (in МН

MN - with Fo u/Fe Ve zm

Ve zn r

AND

Mo nn 1.58 G (3.62 mmol) 6-bromo-3-iodo-M-(tetrahydro-2H-pyran-4-ylmethyl)imidazo

N,2-B|Ipyridazine-8-amine, which was obtained according to Intermediate Example 4440, was converted analogously to Intermediate Example la, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl)/benzamide, yielding after treatment and purification 1.05 g (57 Fo) of the title compound.

Example 446

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-|(3-hydroxyphenyl)amino|imidazo|(1,2-b|pyridazin-3-yl)u.2 -methylbenzamide on on

Fe Fe nm m" / neck nm m" / yuЯ uh be uh

I M M o nn o n zo MG (60 μmol)

M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-((3-methoxyphenyl)amino|imidazo(1,2-5|pyridazin-3-yl)-2- methylbenzamide, which was obtained according to Example 403, was converted analogously to Example 280, obtaining after treatment and purification 9.60 mg (31 95) of the title compound. 1H-NMR (0M50O-ab): b- 0.50 (2H) , 0.65 (2H), 1.18 (6H), 2.37 (ZH), 2.81 (1H), 3.14 (2H), 4.81 (1), 5.88 (1H), 6.33 (1H), 6.49 (1H), 6.94 (1H), 7.03 (1H), 7.23 (1H), 7.32 (1H), 7.77 (1H), 7 .89 (1H), z 8.12 (1H), 8.29 (1H), 8.77 (1H), 9.25 (1H) ppt.

Example 447

M-cyclopropyl-4-16-((3,4-difluorophenyl)amino|-8-K4,4,4-trifluorobutyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide

IR and

MN MN

Fo /F vm / -x nm" m" /

P scha (c) E scha (in 75 mg (15 µmol) 4-(6-bromo-8-(4,4,4-trifluorobutyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)u" M-Cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate Example 447a, was converted analogously to Example 305 using 3,4-difluoroaniline to give, after work-up and purification, 6.3 mg (7 95) of the title compound.1H-NMR (0М5О-46): 6- 0.51 (2Н), 0.66 (2Н), 1.86 (2Н), 2.26-2.43 (2Н), 2.36 (ЗН), 2.81 (1H), 3.32-3.38 (2H), 5.75 (1H), 7.20-7.39 (4H), 7.75 (1H), 7.81 (1H), 7.90 (1H), 7.99 (1H), 8.28 (1H), 9.14 (1H) ppt.

Intermediate Example 447a 4-6-bromo-8-(4,4,4-trifluorobutyl)amino|imidazo|!1,2-5|Ipyridazin-3-yl)-

M-cyclopropyl-2-methylbenzamide was studied

MN

MN p"-x viky

Ve with

And in about 4.27 g (9.51 mmol) of 6-bromo-3-iodo-M-(4,4,4-trifluorobutyl)imidazo(1,2-β|Ipyridazine-8-amine, which was obtained according to Intermediate Example 4470, converted similarly to Intermediate

Example 1a, using M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide, obtaining after treatment and purification 2.37 g ( 50 Fo) of the title compound.

Intermediate Example 447p b-bromo-3-iodo-M-(4,4 4-trifluorobutyl)imidazo|1,2-5|pyridazin-8-amine,

Ve and 28 and -f --» MN

Vg M u/Fe

AND

Ve with ! 3.96 g (9.83 mmol) of 6,8-dibromo-3-iodoimidazo(1,2-b|Ipyridazine, which was obtained according to

Intermediate Example 9bs was converted similarly to Intermediate Example 1, using 4,4,4-trifluorobutan-1-amine, to obtain after processing and purification 3.43 g (74 Fo) of the title compound.

Example 448

M-cyclopropyl-4-16-(5-fluoro-2-methylphenyl)amino|-8-K4,4,4-trifluorobutyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2 -methylbenzamide ich ich

MN MN

Fe Fe vm / Ch-0-k nm m" /

THEIR

U o U o 75 mg (151 μmol) 4-(6-bromo-8-(4,4,4-trifluorobutyl)amino|imidazo|1,2-b|pyridazin-3-yl)u"M-cyclopropyl- 2-Methylbenzamide, which was prepared according to Intermediate Example 447a, was converted analogously to Example 305 using 5-fluoro-2-methylaniline to give, after work-up and purification, 10.5 mg (12 95) of the title compound. ): b- 0.63 (2Н), 0.89 (2Н), 2.00 (2Н), 2.20-2.33 (2Н), 2.30 (ЗН), 2.50 (ЗН), 2.92 (1H), 3.39 (2H), 5.62 (1H), 5.77 (1H), 5.92 (1H), 6.02 (1H), 6.70 (1H), 7 .14 (1H), 7.40 (1H), 7.65 (1H), 7.76 (1H), 7.84 (1H), 7.87 (1H) ppt.

Example 449

M-cyclopropyl-4-/6-|(Z-fluoro-

B-methylphenyl)sulfanyl/|-8-(4,4,4-trifluorobutyl)amino|imidazo|!1,2-5|Ipyridazin-3-yl)y-2-methylbenzamide and you

МН Ко ве / -б0к Е vm / nm? o M 75 mg (151 μmol) of 4-(6-bromo-8-(4,4,4-trifluorobutyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide , which was obtained according to Intermediate Example 447a, was converted analogously to Example 51 using 3-fluoro-5-methylbenzenethiol to give, after work-up and purification, 44.6 mg (50 95) of the title compound. 1H-NMR (SOSIS): 6 - 0.63 (2H), 0.90 (2H), 1.97 (2H), 2.23 (2H), 2.36 (ЗН), 2.41 (ЗН), 2.92 (1Н), 3.38 (2H), 5.79 (1H), 5.87 (1H), 5.91 (1H), 6.96 (1H), 7.17-7.29 (ЗН), 7.66 ( 1H), 7.69 (1H), 7.72 (1H) ppt.

Example 450

M-cyclopropyl-4-16-(2,3-difluorophenyl)amino|-8-K4,4,4-trifluorobutyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide

E E their ich

MN MN

/F /Fo vm / shi nm m" / vo

IS

U o U o 75 mg (151 μmol) 4-(6-bromo-8-(4,4,4-trifluorobutyl)amino|imidazo|1,2-b|pyridazin-3-yl)u"M-cyclopropyl- 2-methylbenzamide, which was obtained according to Intermediate Example 447a,

was converted similarly to Example 305, using 2,3-difluoroaniline, to obtain after processing and purification 10.6 mg (12 95) of the title compound. 1H-NMR (SOSIS): b- 0.63 (2H), 0.90 (2H), 2.03 (2H), 2.28 (2H), 2.52 (ZH), 2.93 (1H) , 3.43 (2H), 5.64 (1H), 5.75 (1H), 5.91 (1H), 6.40 (1H), 6.81 (1H), 7.03 (1H), 7.40 (1H), 7.66 (1H), 7.78 (1H), 7.98 (1H), 8.07 (1H) ppt.

Example 451 4-6-(5-chloro-2-methylphenyl)amino|-8-K4,4-4-trifluorobutyl)aminoimidazo

P,2-Shipyridazin-3-yl)-N-cyclopropyl-2-methylbenzamide ich ich

MN MN

Fo /Fo web / - nm m" /

IN

U o u o 75 mg (151 μmol) 4-(6-bromo-8-(4,4,4-trifluorobutyl)amino|imidazo|1,2-b|pyridazin-3-yl)u"M-cyclopropyl- 2-Methylbenzamide, which was prepared according to Intermediate Example 447a, was converted analogously to Example 305 using 5-chloro-2-methylaniline to give, after work-up and purification, 12.7 mg (14 95) of the title compound. ): b- 0.61 (2H), 0.88 (2H), 1.99 (2H), 2.17-2.38 (2H), 2.29 (ЗН), 2.48 (ЗН), 2.92 (1H), 3.38 (2H), 5.60 (1H), 5.73 (1H), 5.90 (1H), 5.98 (1H), 6.99 (1H), 7 .13 (1H), 7.43 (1H), 7.65 (1H), 7.76 (1H), 7.91 (1H), 7.93 (1H) ppt.

Example 452

M-cyclopropyl-4-16-(3-fluoro-5-methylphenoxy)-8-(4,4,4-trifluorobutyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide ich

MN Co

Ve zm 7 --» E o zi J

H neo o XM ho b 75 mg (151 μmol) 4-(6-bromo-8-(4,4,4-trifluorobutyl)amino|imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl -2-methylbenzamide, which was obtained according to Intermediate Example 447a, was converted analogously to Example 51 using 3-fluoro-5-methylphenol to give, after work-up and purification, 27.7 mg (32 95) of the title compound. 1H-NMR ( SOSIZ): b- 0.60 (2Н), 0.88 (2Н), 2.04 (2Н), 2.28 (2Н), 2.34 (ЗН), 2.37 (ЗН), 2.90 (1H), 3.46 (2H), 5.81-5.89 (ZH), 6.7 7-6.687 (ZH), 7.27 (1H), 7.66 (1H), 7.73 ( 1H), 7.77 (1H) ppt.

Example 453 4-(6--(cyclopentylamino)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-B)pyridazin-3-yl)y"-M-cyclopropyl-2-methylbenzamide

E E

E E

RU o RU mo MN de 4 ;sh y

In o In o

To a solution of 90 MG (153 μMOL) tert-butyl (6-(cyclopentylamino)-3-(4-(cyclopropylcarbamoyl)-3-methylphenylimidazo(1,2-b|pyridazin-8-yl3,3,3-trifluoropropyl)carbamate , which was obtained according to Intermediate Example 453a, 177 μl of trifluoroacetic acid was added to 1 ml of dichloromethane, and the mixture was stirred for 2 hours at 23 "C. The mixture was poured into water and extracted with dichloromethane. The organic phase was washed with sodium hydrogen carbonate solution and dried over sodium sulfate. After filtering and removing the solvent, the residue was purified by chromatography to give 64.1 mg (82 95) of the title compound.1H-NMR (OM50-46): b- 0.50 (2H), 0.64 (2H), 1 44-1.72 (6H), 1.90-2.05 (2H), 2.34 (ZH), 2.62 (2H), 2.79 (1H), 3.41 (2H), 3, 99 (1H), 5.57 (1H), 6.43 (1H), 6.92 (1H), 7.30 (1H), 7.73 (1H), 7.98 (1H), 8.17 (1H), 8.24 (1H) ppt.

Intermediate Example 453Za 4-(6--(cyclopentylamino)-8-((3,3,3-trifluoropropyl)aminoyl|imidazo|1,2-b|pyridazine-

C-yl)uN-cyclopropyl-2-methylbenzamide

IS

E and RU ok sa ok mo mo Se

OR,

Days of M -- nyu M /F, 5 of them are M

And about 135 mg (250 μmol) tert-butyl

1b-(cyclopentylamino)-3-iodoimidazo(1,2-b|pyridazin-8-yl)(3,3,3-trifluoropropyl)carbamate, which was obtained according to Intermediate Example 4536, was converted similarly to Intermediate

Example And, using (|4-(cyclopropylcarbamoyl)-3-methylphenyl|boronic acid, obtaining after treatment and purification 101 mg (65 95) of the title compound.

Intermediate Example 4535 tert-butyl |b-(cyclopentylamino)-3-iodoimidazo(1,2-b|pyridazin-8-yl|(3,3,3-trifluoropropyl) carbamate

E E

E E a oh a ok mo mo du tod

NM with NM with o o 197 MG (405 μmol) tert-butyl

1b-(cyclopentylamino)imidazo|1,2-b|pyridazin-8-yl)(3,3,3-trifluoropropyl)carbamate, which was obtained according to Intermediate Example 453c, was converted similarly to Intermediate

Example 9bs with obtaining after treatment and purification 141 mg (58 95) of the compound indicated in the title.

Intermediate Example 453c tert-butyl |b-(cyclopentylamino)imidazo(1,2-b|pyridazin-8-yl)|(3,3,3-trifluoropropyl)ucarbamate

IS

IS

And J In approx

U o motu 7 u/Fe 5. M / new M veins ХУ 200 mg (489 μmol) tert-butyl (6-Bromoimidazo|1,2-b|pyridazin-8-yl)(3,3,3-trifluoropropyl ) of the carbamate, which was obtained according to Intermediate Example 4534, was converted similarly

Intermediate Example 305, using cyclopentanamine, with treatment and purification yielding 205 mg (101 90) of the title compound containing a certain amount of reagent.

Intermediate Example 4534 tert-butyl (6-bromoimidazo(|1,2-b|Ipyridazin-8-yl)(3,3,3-trifluoropropylcarbamate

E E

E E

RU Ro

MN --- mo

Ve with Ve dick

To a solution of 1.88 g (6.08 mmol) b-bromo-

M-(3,3,3-trifluoropropyl)imidazo|1,2-b|Ipyridazin-8-amine, which was obtained according to Intermediate

Example 453e, 2.92 g of di-tert-butyl dicarbonate, 74.3 mg were added to 7.0 ml of tetrahydrofuran

M, M-dimethylpyridin-4-amine, and the mixture was heated for 2 hours at 55 "C. Ethyl acetate was added, and the organic phase was washed with saturated sodium bicarbonate solution and dried over sodium sulfate. After filtration and removal of the solvent, the residue was purified by chromatography to give 2.15 g (82 9o) of the compound specified in the title.

Intermediate Example 453e b-bromo-M-(3,3,3-trifluoropropyl)imidazo|1,2-5|pyridazin-8-amine

IS

IS

Ve U ak -- zhk MN

Phew!

Ve M s b;

Weight 5.00 g (18.06 mmol) of 6,8-dibromoimidazo(1,2-B|Ipyridazine, which was obtained according to

Intermediate Example 96ba was converted similarly to Intermediate Example 16, using 3,3,3-trifluoropropan-1-amine, to obtain after treatment and purification 3.04 g (49 Fo) of the title compound.

Example 454

M-cyclopropyl-4-16-|((3-hydroxy-2-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl )u.2-methylbenzamide

And I

In U

MN MN

/F5 /Fe

NM zm / -- - NM zm / ve ve

U o U o 141 MG (26 μmol) M-cyclopropyl-4-16-|(3-methoxy-2-methylphenyl)amino!|-8-(3,3,3-trifluoropropyl)amino|imidazo(1,2 -b|pyridazin-3-yl)y-2-methylbenzamide, which was obtained according to Example 426, was converted analogously to Example 280, obtaining after treatment and purification 4.7 mg (33 95) of the title compound. 1H-NMR (0M50-avb): 0-0.48 (2H), 0.64 (2H), 2.04 (ZH), 2.23 (ZH), 2.60-2.82 (ZH), 3.48 (2H), 5.94 (1H), 6.58 (1H), 6.95 (1H), 7.06-7.29 (ZH), 7.79 (1H), 7.81 ( 1H), 7.93 (1H), 8.03 (1H), 8.22 (1H), 9.24 (1H) ppt.

Example 455 4-(6--(cyclopentyloxy)-8-I|(3,3,3-trifluoropropyl)amino|imidazo|1,2-B)pyridazin-3-yl)y"-M-cyclopropyl-2- methylbenzamide ve

E ts i

In MN

MN Se

ХТ, se --jav v) M (o; i, o

I o B 32 mg (73 μMOL) of 6-(cyclopentyloxy)-3-iodo-M-(3,3,3-trifluoropropyl)imidazo|1,2-b|Ipyridazine-8-amine, which was obtained according to the Intermediate Example 455a, converted similarly to Intermediate Example 1a, using

14-(cyclopropylcarbamoyl)-3-methylphenyl|roronic acid, obtaining after treatment and purification 17.4 mg (47 95) of the title compound. 1H-NMR (SOSIS): b- 0.65 (2H), 0.91 (2H), 1.50-1.73 (6H), 1.84 (2H), 2.40 (2H), 2, 48 (ZH), 2.94 (1), 4.08 (2H), 4.82 (1H), 5.26 (1H), 5.93 (1H), 7.10 (1H), 7.13 (1H), 7.40 (1H), 7.45 (1H), 7.64 (IN) ppt.

Intermediate Example 455a b-(cyclopentyloxy)-3-iodo-I-(3,3,3-trifluoropropyl)imidazo|1,2-b|Ipyridazin-8-amine

EYE EEE

In U

42 MG (134 μmol) 6-(cyclopentyloxy)-M-(3,3,3-trifluoropropyl)imidazo

P,2-B|Ipyridazine-8-amine, which was obtained according to Intermediate Example 4550, was converted analogously to Intermediate Example 9bs to obtain, after treatment and purification, 33 mg (56,965) of the title compound.

Intermediate Example 455p b-(cyclopentyloxy)-M-(3,3,3-trifluoropropyl)imidazo|1,2-b|pyridazin-8-amine

E E

E E a ok RU mo MH po Zo de ge ge 361 mg (max. 784 μmol) tert-butyl (|b-(cyclopentyloxy)imidazo|1,2-b|pyridazin-8-yl (3,3,3- trifluoropropyl)ucarbamate, which was obtained according to Intermediate Example 455c, was converted similarly to Example 453, obtaining after processing and purification 43 mg (17 95) of the title compound.

Intermediate Example 455c tert-butyl |b-(cyclopentyloxy)imidazo|1,2-5|Ipyridazin-8-yl|(3,3,3-trifluoropropyl)ucarbamate

IS

E vok shchi g

U (o; mo u/Fe OM Y om

VI zy o

321 mg (784 μmol) of tert-butyl (6-Bromoimidazo|1,2-b|Ipyridazin-8-yl)(3,3,3-trifluoropropyl) carbamate, which was obtained according to Intermediate Example 4534, was converted similarly

Intermediate Example 51, using cyclopentanol, to give after workup 361 mg of the title compound containing the starting material and products where the carbonate was cleaved.

Example 456

M-cyclopropyl-4-16-|((5-hydroxy-2-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl )u.2-methylbenzamide

And I

In U

MN MN

/F5 /Background change / --5 change background /

F 7 F "on

U o U o 10.5 MG (19 μmol)

M-cyclopropyl-4-76-((5-methoxy-2-methylphenyl)amino1|-8-((3,3,3-trifluoropropyl)amino|imidazoi|1,2-B pyridazin-3-yl/-2 -methylbenzamide, which was obtained according to Example 430, was converted analogously to Example 280 to obtain, after treatment and purification, 2.0 mg (18 95) of the title compound. , 0.64 (2H), 2.21 (ZN), 2.24 (ZN), 2.60-2.83 (ZN), 3.48 (2H), 5.94 (1H), 6.42 (1H), 6.95 (1H), 7.10 (1H), 7.16 (1H), 7.20 (1H), 7.79-7.90 (ЗН), 8.01 (1H), 8.21 (1H), 9.06 (1H) ppt.

Example 457

M-cyclopropyl-4-76-((4-fluoro-2-methoxyphenyl)amino|-8-K4,4,4-trifluorobutyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)y-2 -methylbenzamide ich ich

MN MN

/F /Fo ve / T-x them" / 7 "in (in E shchi (in) 150 mg (302 μmol) 4-6-bromo-8-(4,4,4-trifluorobutyl)amino|imidazo|1, 2-5|pyridazin-3-yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 447a, was converted analogously to Example 305, using 4-fluoro-2-methoxyaniline, to give after work-up and purification 43, 1 mg (24 95) of the title compound 1H-NMR (SOSIS): b- 0.65 (2H), 0.91 (2H), 2.02 (2H), 2.28 (2H), 2, 54 (ЗН), 2.94 (1Н), 3.42 (2Н), 3.92 (ЗН), 5.58 (1Н), 5.66 (1Н), 5.93 (1Н), 6.63 -6.71 (ZH), 7.41 (1H), 7.63 (1H), 7.81 (1H), 8.01 (1H), 8.28 (1H) ppt.

Example 458

M-cyclopropyl-4-76-(2-fluoro-3-«(methylsulfanyl)phenoxy)|-8-K(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl )y-2-methylbenzamide on on

Ve zm / Ge) zm / vo i

U o U o 2.00 g (4.536 mmol) 4-(6-bromo-8-K(2-hydroxy-2-methylpropyl)amino|midazol|1,2-5|pyridazin-3-yl)"M- of cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate Example 9ba, was converted analogously to Example 51 using 2,3-difluorophenol to give, after work-up and purification, 4.6 mg (0.2 95) of the title compound and 933 mg ( 42 95) of the title compound described in Example 92. 1H-NMR (OM5O-ab): b- 0.50 (2H), 0.67 (2H), 1.21 (6H), 2.14 (3 ), 2.52 (ZH), 2.80 (1H), 3.33 (2H), 4.78 (1H), 6.27 (1H), 7.05 (1H), 7.17 (1H) , 7.26 (1H), 7.28-7.34 (2H), 7.64 (1H), 7.70 (1H), 7.95 (IN), 8.23 (1H) ppt.

Example 459 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazin-3-yl)y-2-methyl-M-(1 -methylcyclopropyl)benzamide

IS

E eE Ii U

IN

MN

MN in the afternoon. 2-Y 5 M Y --» OM om

Guo Yu

Eh oh we oh no koh

A mixture containing 10.5 mg (22 μMOL) 4-(6-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl) y-2-methylbenzoic acid, which was obtained according to Intermediate Example 459a, 3.94 mg of 1-cyanocyclopropanaminium chloride, 12.6 mg of M-Kdimethylamino)(ZH-|(1,2,3|griazolo

I4,5-B|Ipyridin-3-yloxy)methylene|-M-methylmethanaminium hexafluorophosphate, 4.06 mg M,

M-dimethylpyridin-4-amine and 0.5 mL of M,M-dimethylformamide were stirred at 23 °C overnight. The solvent was removed and the residue was purified by chromatography to give 4.5 mg (36 95) of the title compound. 1H-NMR (0М5О-46): 6- 1.21 (2Н), 1.50 (2Н), 2.16 (ЗН), 2.68 (2Н), 3.60 (2Н), 6.14 (1Н), 7.14 (2H), 7.25 (2H), 7.49 (1H), 7.67-7.76 (2H), 7.81 (1H), 7.97 (1H), 9.09 ( 1H) ppt.

Intermediate Example 459a 4-(6-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)y-2-methylbenzoic acid p

R

MN

M MN sashe sia o se om --ke CHI, om

Y H is Y

ME

(c) M oon

A mixture containing 231.8 MG (451 µMOL)

M-cyclopropyl-4-76-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, which was obtained according to Example 80, and 7.73 ml of hydrobromic acid was heated at 120 "C for 10 hours. Water was added, the precipitate was filtered and purified by chromatography to give 74 mg (24 9b5) of the title compound, which contained about 30 95 4 -16-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino|midazol|1,2-5|pyridazin-3-yl)y-2-methylbenzamide.

Example 460 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazin-3-yl)-N-(1-methoxycyclopropyl)-2- methyl benzamide

IS

IS

What RU

MN se sa 2 KI Y

WITH -

S. Go

Ho -

E neo (c) no ex 10.5 mg (22 μmol) 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazine- 3-yl-2-methylbenzoic acid, which was obtained according to Intermediate

Example 459a was converted similarly to Example 459, using 1-methoxycyclopropanaminium chloride, to obtain after processing and purification 10.7 mg (85,965) of the title compound. 1H-NMR (0M50O-ab): b- 0.84 (2H), 0.97 (2H), 2.15 (ZH), 2.68 (2H), 3.24 (ZH), 3.60 ( 2H), 6.13 (1), 7.09-7.16 (2H), 7.21 (1H), 7.25 (1H), 7.49 (1H), 7.67 (1H), 7 .71 (1H), 7.78 (1H), 7.94 (1H), 9.04 (1H) ppt.

Example 461 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazin-3-yl)y-2-methyl-M-(1 -methylcyclopropyl)benzamide

IS

E eE Ii U

IN

MN

MN in the afternoon with 2-8 with, .M and 5 Y --- OM om uv d

E (c) 10.5 MG (22 μmol) 4-(6-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl) of y-2-methylbenzoic acid, which was obtained according to Intermediate Example 459a, was converted analogously to Example 459 using 1-methylcyclopropanaminium chloride to give, after work-up and purification, 12.0 mg (98 95) of the title compound. 1H-NMR (SOSIS): b- 0.74 (2H), 0.85 (2H), 1.51 (ЗН), 2.31 (ЗН), 2.58 (2Н), 3.68 (2Н) , 5.89 (1H), 5.99 (1H), 6.07 (1H), 6.94-7.09 (ZH), 7.23 (1H), 7.39 (1H), 7.61 (1H), 7.73 (2H) ppt.

Example 462 3-(3-amino-1H-indazol-b-yl)-6-(3-fluorophenoxy)-M-(3,3,3-trifluoropropyl)imidazo|1,2-b|Ipyridazin-8-amine ve

E and U

In MN

MN NO. don Dn M a Dx 5-Y

THEIR family is the NMOMN. 7 And here

E c) M E

Ve

THOSE m pk me Mn,

42 MG (100 μmol) 3-bromo-6-(3-fluorophenoxy)-IM-(3,3,3-trifluoropropyl)imidazo

P,2-B|Ipyridazine-8-amine, which was obtained according to Intermediate Example 46b2a, was converted analogously to Example 101, using (4-cyano-3-fluorophenyl)boronic acid, to obtain 2-fluoro-4-(6-( 3-Fluoro-phenoxy)-8-(3,3,3-trifluoro-propylamino)-imidazo

P,2-Shipyridazin-3-yl|-benzonitrile. 62 μl (2 mmol) of hydrazine hydrate was added, and the mixture was heated at 80 C overnight. After processing and purification, 5.1 mg (11 95) of the title compound was obtained.

ORI O-M5: KET-1.14, MUU detected - 472.4, MMU calculated - 471.4. LN-NMR (300 MHZ, рм50-а6), b Irritability - 2.65 (ЗН), 3.58 (ЗН), 5.32 (2Н), 6.06 (1Н), 7.00-7.21 (ЗН), 7.38 (1Н), 7.49 (1Н), 7.59 (1Н), 7.73 (1Н), 7.83 (1Н), 7.91 (1Н), 11.91 ( 1H)

Intermediate Example 462a

Z-bromo-6-(3-fluorophenoxy)-M-(3,3,3-trifluoropropyl)imidazo|1,2-b|pyridazin-8-amine in these I I

MN MN dune

Ve no What he is about and

Bg Be 448.9 mg (1.16 mmol) of 3,6b-dibromo-M-(3,3,3-trifluoropropyl)imidazo(1,2-b|Ipyridazin-8-amine, which was obtained according to Intermediate Example 46260 , was converted analogously to Example 51 using 3-fluorophenol to give, after workup and purification, 105.7 mg (22 95) of the title compound. 1H-NMR (300 MHz, OM5O-ab), 6 Irrti: 2.55-2 .73 (2H), 3.55 (2H), 6.06 (1H), 7.00-7.09 (2H), 7.11-7.22 (1H), 7.33-7.49 ( 1H), 7.56 (1H), 7.82 (IN)

Intermediate Example 462

3,6-dibromo-M-(3,3,3-trifluoropropyl)imidazo(1,2-5|Ipyridazin-8-amine

IS

IS

That M E E is yours

Fe, - and that's it

Vg M and MM

Ve SI MN» PTO -/

Vg 3.00 g (8.43 mmol) of 3,6,8-tribromoimidazo|(1,2-B|pyridazine, which was obtained according to

Intermediate Example 462c was converted similarly to Intermediate Example 16, using 3,3,3-trifluoropropane-1-aminium chloride, to obtain after processing and purification 2.97 g (91 95) of the title compound. 1H-NMR (300 MHz, OM5O-avb), b Irrtui: 2.52-2.73 (2H), 3.56 (2H), 6.45 (1H), 7.61 (1H), 8.01 (tn)

Intermediate Example 462c 3,6,8-tribromoimidazo|1,2-b|Ipyridazine

Ve Vg dom se

She, Ve and

Ve

69.2 g (433, 3 mmol) of bromine at room temperature, and the mixture was stirred for one hour. The sediment was filtered, washed with water and dissolved in 10 l of OSM. The organic phase was washed with saturated sodium bicarbonate solution, dried over sodium sulfate, filtered and evaporated to give 81.99 g (64 95) of the title compound. 1H-NMR (400 MHz, OM5O-46), b (rrtui- 7.96 (1H), 8.04 (1H).

Example 463

M-cyclopropyl-4-76-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazine-3-ilubenzamide in in o MN

MN where that and . E o M du t"

E (c) MA

Vg 42 mg (100 μmol) 3-bromo-6-(3-fluorophenoxy)-IM-(3,3,3-trifluoropropyl)imidazo

P,2-B|Ipyridazin-8-amine, which was obtained according to Intermediate Example 462a, was converted analogously to Example 101, using (4-(cyclopropylcarbamoyl)phenylboronic acid, obtaining after treatment and purification 2.9 mg (5 95) of the specified in the compound header.

ORI O-M5: KT-1.31, MUU detected - 500.5, MMU calculated - 499.5. 1LN-NMR (300 MHz, rm50-a6), b (rrtd|- 0.52 (2H), 0.66 (2H), 2.67 (2H), 2.79 (1H), 3.59 (2H ), 6.14 (1H), 7.08-7.17 (2H), 7.24 (1H), 7.33-7.60 (2H), 7.68 (1H), 7.77 (1H ), 7.95(1H), 8.01 (1H), 8.40 (1H).

Example 464

M-cyclopropyl-4-[6-((5-fluoropyridin-3-yl)oxy1|-8-((3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl) y-2-methylbenzamide in I I I

MN MN in 99 n E that -

48 mg (100 μmol) 4-(6-bromo-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-5|Ipyridazin-3-yl)u"M -cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 247a, was converted analogously to Example 51 using 5-fluoropyridin-3-ol, obtaining after treatment and purification 8.1 mg (16 95) of the title compound.

ORI O-M5: KET-1.19, MUU detected - 515.5, MMU calculated - 514.5. 1LN-NMR (300 MHz, rm50-ab6), 6 (rrite 0.41-0.54 (2H), 0.58-0.71 (2H), 2.14 (ZN), 2.59-2, 85 (ZH), 3.61 (2H), 6.21 (1H), 7.17 (1H), 7.61 (1H), 7.70 (1H), 7.81 (1H), 7.93 (1H), 7.95-8.06 (1H), 8.22 (1H), 8.46-8.63 (2H)

The following examples of compounds were prepared analogously to the procedure described in Example 51 using the appropriate phenols or anilines (LC-MS data such as retention time (QT in min) or mass peak observed were collected using LC-MS Method A until otherwise indicated|:

Application Structure of Deva Anapite data of 1125 Muu has been discovered

Its 8295 MUU is calculated "

BIV

Ki. . in 446-(2-amine-5-fluorophene | LE-NMR (300 che | scxi)-8-((3.3.3-trifluorop | MGU OMBO-a8),. « рр» ve i te | ropgdeminoimidazog tt 043- 051 (one), 058-068 ri! mass I Ipyridazine-3-(2H), 215 (ZN); bvoava shu | ily-M-cyclopropyl-?-meth | (ZN), 3.59 (28), 4.83 (2Н), ов | ilbenzamide in NA 6,748.89 IN),

Sh | 885 (IN), 7.03 IN TB (an) 781-770 (on), 7.84.

SHSH (NO; 792 (1), 22 IN)

CT x 1.36 MUU detected x 521.6 MUU calculated - 50.6

NAM (600 in MHz MBO) » Trrtiye in M-cyclopropyl-2-matyl I 0480054 (2, 083-070

VE 4-45-41523, А-tetrahydroch sk Zh z y sho (OH), 1.78-1.82 (28), 279

AI oU nalin-8-yloxyi-8-K3,5,3- I 458 vych 0 18Nu, 2-28 (48), 2,80 rich trifluoropropylamine|yme | o koe et I (IN), 3.12-3.20 (9), 3.61 times the dose of 2-vipyridazine) - More

VN M 2). 5.24 (IN, because KN). ku ilibenzamide ha bo nu 662 (18) 5 OO

I YANU 718 (NO, 7.60 (B,

Tta-t (NU 78 IN), 7.951183, 8.23 (18)

CT - 119 MU detected with 551.6 MU calculated -

FOR

1NYAMe (800 in MHz OoM5O-av), is рrti: ve M-cyclopropygYa(b-(vVyai and ! irrgvi 07055 (2) 08607

Z droxy-Z 4-dihydroquinali" I and that M ku .. (NI, 1882), 231 (ZV),

Kg nenya three 487 sewed | Also 2.62 (2H), 2.69 (2H), 2.83 and fluoropropylaminoimidase: | And what 2 | (NU, Zla (2H), 3.84 (2H), another 1 and 1,2-vipyridazine-Z-I

VK umi | | 572 (Nv NN), 874 your IP 2-methylbenzamide | what they are (189), 6.50-8.94 (1), 7

Is it 72? IN), 7, in4 (H).;

And 7.82 (JAN), 796 (1Н) 825 (18), 9.29 (11) ivoteny!

And I sh--

KT-01 МХ revealed 583.5 ММ calculated - 525 in ZBYАMe (600 in M-cyclopropyl-2-methyl- | Mgz OM5O-a6), - Grrti: vn A-6-|(O-oxo- 047-051 ( 2. 054-065 lev g so 1,2-dihydroquinoline-Villiu | (2H), 2.08 (3H), 2.71-2.82 me xyr8-(3,3,H-trifluoroir | (33, 3.66 (28), 625: (H), which is propyl)aminoimidazog, 2-5) 18.55 (1). 7.08 (IN), 728 p pyridazinoZ-ilibenzamide (1). 7.54 (183. 7.57 (IN),

Sh 782-755 (Nu Tav-t

IN, 7.95 (18), 802 (1), won)

W - 095 MUU detected " 565.8 MUU calculated "

Y 5646 and 1IN-NMR (300 h M-cyclopropyl-d-methyl- | MHC OM5O-ab i Grrtie in 4-02 -methyl-1i Zate | 049-050 (2) 058-068 zvo | g ie trahydroisoquinoline-ite (28). 2,095 (3NuU, 2528 (ZN), 485 ikod kody veda | Й

SODU 0 neeaaayariftoror 253 (9), 260281 (BN),

Ot no ophil)amino|imidazoi 2-5 351 (2), 3.59 (2),

And pyridazine-3-yl)benzamide (18). 897-706 (29, 712 (well at724 (well

BA in? (as well as NU, 7.91 (in), BB)

I Z M-cyclopropyl-2-methyl-a Z 4-(6-(3-methylphenoxime B. | VT 1.42 MU was found to be AK Ai 4(3,3.3-trifluoropropyl)a | 510.5 MAM was calculated - ! I mino|midase 1, 2-Euipyride | 509.5 no U I zin-3-ipibenzamide: food

What | Tue "1.34 MM detected - ! 525.5 MMUU calculated - 525.5

INYAME (400 kA M-cyclopropylaYava4-m | MHC OOM5O-YAB), I Trrtiye

It is ethoxyphenoxy)p8-(3558 and 03050 (NI 060-088 471 shk; "trifluoropropyl)aminoim (BO, 21 (ZNO, 260-273 kiidazoi1,2-B)pyridazine-Z- | (2H), 9.77 (18), 3.592Н), and ily-2-methylbenzamide 375 (ZN), BO? (in), 6.99 (dn 7.13-t.22 (zNi, (58-77 (NU TU pe tight nI

ICT- 1.46 MUU detected 514.5 MUU calculated xz ki 1NyaMe (400

SH Mecyclopropyl-4-(v-(4-f | Mgo OMeO-Ya6) - (rt) and sc torphenoxy)-8-C3.3,3-tr 047 (28), 0.63 (28), 2, 13 se M here in pofrtorpropylaminoimida | (ZM), because the UN,

Ba. 3011 2-B|pyridazine-Z- 273-282 IN). 380 (2), ! on shchy-yan yl-2-methylienzamide BO in A

To UZ, (4), 7.80-7.70 (an), 7t2 NU U, 92 IN, wagons

Application | Structure Name Analytical data ! And! i i Mecyclopropyla- Va 7 se Kot torphenoxy)- 8-3 3Z-tr | CT 5 11/38 MUM revealed - 473 voFe; | 2-Vipyridazine-3-513.5 sodium octylpre-methylbenzamide, ! M-cyclopropyl-methyl "Mn | I I ! re peschikh 448-42-methyphenoxy)-y (KT ex 1.40 MM was found x t, 414 Mokoichtsii 8.3, Z.trifluoropropyl)a 510.5 MUU calculated « sn , With minokmidazo and a vipirida | 509.5 be ; And pe oicyan - zin-Z-ilibenzamide her in Mocycloprolip-4-164 (3-

E nn fluor-Y: ve Ische and KT 2 1.35 MUM revealed that! : she ve ny ox sa i-methoxyphenoxy)v4(3 ! 475 Kc live 5445 MUM calculated zh i "Z,Z-trifluoropropylamine v sh what 543.5 . v imidazoig 2-5 tridazine I i -Zal)-2-methylbenzamide .

VT "g 0.89 MUu was found xz zad MU calculated x n 553.5 shk 4-(8-D4-(acetipaminoipir | TYM (300

The same idine-Z-ipoxy)-8-(3.3.3-| MGn MOV), i Grr)ie it re - g trifluoropropyl)aminoimy | 0.44-0.55 (28), 0.60-0.65

M dit V i s I grief

2-Vipyridazine-3Я | (2H), 2520-2527 (ZN), 2.38 th "AMK with that and vu pr M-tsIkpopromy-o-mety | (ZN); 2.85-2.85 (ZN). 369 o X lbenzamid | (2H), 876 (IN), 78 (1),

And | 784-793 23, 7955804 (2), 8.09 (1H), 8.23-8.34 and ZA), 836 1)

pi

Structure Name Analytical data

VT 2 198 MUM detected t 525.5 MUU calculated - 528.5 ! in av amino-3-fluorob 1H:YMe U z -in-(2:amino-3-fluorophen o ,

More | Mgts OMBOchiv), - (movement of vn oxy)-8-3 3 Z«triftorp and tk A Kk ; , 042-053 (2 05850695

DOA ropyliuaminoimidazog and 2-8 | pi 47 AJ zhi and Sho (2), 9.13 (ZMI, 2.59-2.85.

M M nya fpridazine-3- | What!

Mn, 23 and | (Z), 3.50-3.86 (28), 498. pr iprMeUcyclopropyl-e-meth. and pen nu wl In, 653-663 and ipbaenzamid

Tu (14). 6ez (H), bot

MON" 74 (n) tvolvv, (NA Y, 80 SN TV

In) in2? in)

ET 110 MUH was discovered t

BIV MU calculated - 528.5 in | | 1AYAME (300 v. Mcyclopropyl-4-8-Tsashi and Mgu oM5O-a6), that is fluorine and also known | . 49 3; 589 yo

E mk mino|muazog i bntrida 1 , I y

BU bB.B-B and (2) 689 chezin-Z-anischi; ve i lo 0 (2),

And ip-a-methylbenzamide! and | and ot6vlt5 (Nu t Nu. ot7,82 IN 78? IN OV

ZY av (Well Boteg! seh

KT 141 MUM was found: 510.5 MU was calculated

IS ! 509 ko; And 1H-NMR (360 and Mecyclopropyl-2-methyl-

KN p. | MHz MBO) « Trrtiye nd. oo a be-methypoenoxyv pn shk m ne sho 042-050 (2) 055067 479 Languages Y (353-trifluoropropita | S. ! sho Y ni M Shcho en) 28 (ZM) 231 (ZN),

Sak minonmidazoi 1,5-viprida in SHO | 258-282 (3). 358 (9), but also zin-Z-upbenzamide and M o M VV (NI, 15 IZ), 755

SHY (28), 760-768 (2), 7.75 anutesinuvain and What is 1.255 MUU revealed and 529.5 MUU calculated -

BV B schi | in-yame (300 in M-cyclopropyli-o-CYA-| that , shk ! and MG OoMaO-av), - Trrytse "MV Ftovr-pu s mok SH OR BA (2 060-071 t ve 2-hydroxyphenyl)iaminoi In |. also I

And Kyiv | (2H); 253333, 2.67 (2) 480 m -KZU3,Z-trifluoropropyl)a What are you and what | 2.80 (1). 343-353 (2),

TT UA minomidazo 2 Biprida What to use | 8.1 (NO 6,535 663 (1),

KOM and zin-3-pishche Shk chu | | 6.67 (1H), 718 (1H), 7.30

M ili-ia-methylbenzamide I I:

Her (NN 756 (14 778-785 (1), 790 (1), 7.98-8.14 (3) 828 ST). TOM) ka CT 0.84 MUU revealed - -- MucykpopropinnYayaya VZ s and I 00001 512.5 MUU was calculated - in droxypridine-a- amino I and I sake oi1-8-4(3,3, Z-trifluoroprop Sh and

EE she; (300 units of ipaminomidase)

In Z Mha OoMBONav) i roti: also idazin-3- o, ee 047-056 (28U 062-071 ah ipra-methyloenzamide SHY and SY them! (en; 239 (3), 268 (28,

2.82 (NU 345-356 (28), women (1), 7.32-7.49 (21),

U -TVB (EN VV NO, ob nu ovv (1), Ve (nu, vev(oN)

Example 482

M-cyclopropyl-2-methyl-4-16-(1-phenylethenyl)-8-(3,3,3-trifluoropropyl)amino|imidazo|/1,2-5|pyr

E Mr

Nt nm

KI Fe

Vg Zm | y: zm And here is Mo vu on nm? dazin-3-ilibenzamide and"

To the mixed solution, 24 mg (50 μmol) of 4-16-bromo-8-K(3,3,3-trifluoropropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)U-M-cyclopropyl-2 -methylbenzamide, which was obtained according to Intermediate Example 247a, in 1 ml of TNE, 1.0 ml (0.5 mmol) of a 0.5 M solution of bromo(1-phenylethenyl)magnesium in TNE was added dropwise at room temperature. After stirring overnight at room temperature, the mixture was heated at 50° and stirred for another 3 days to give, after workup and purification, 1.7 mg (5 95) of the title compound.

ORI O-M5: KT-1.36, MUU detected - 506.5, MMU calculated - 505.5. 1LN-NMR (400 MHz, rm50-ab6), 6 (rrite 0.42-0.50 (2H), 0.59-0.66 (2H), 2.15 (ZN), 2.61-2, 71 (2H), 2.77 (1H), 3.60 (2H), 5.74 (1H), 5.99 (1H), 6.36 (1H), 7.16-7.20 (2H) , 7.34-7.45 (ЗН), 7.55 (2Н), 7.79-7.84 (1Н), 7.86 (1Н), 8.01 (1Н), 8.22 (1Н)

The following examples of compounds were prepared analogously to the procedure described in Example 482 using the appropriate Grignard Idani reagents LC-MS, such as retention time (CT in min) or observed mass peak was collected using LC-MS Method A unless otherwise noted|:

pinpppins

Pricks with Structure Name Anapitichi! data about W 1.33 MU ! | discovered with

And 5425 MU. and calculated - 541.5

yum (400

Mgz oMmBO-a is Gb i rogu no | 0.47-0.53(2NO,

E i c ilnvchvChzer 0.62-0.69(2Н).

A vysh and Mecyclapropyl-ia b rtornebu te, 2.82 (ZH), 2.64 i 4-methoxybenzit-B- KZ, 3, Z-trift 483 nina and (2) 2277-24 ron erpropyl)amino midazoi 3 2-01pvry

Kshchyton | well 383 tk: ih Z: shh : . in dazin-zpi-2-methylbenzamide.

Leo (2). 3.76 pits! schi these

M (ZR). Sat (en), 5.20 pn" then 12). 717-723

Mon). 7.3

SN, 747 (IN), 7.93-7.98 (NU vo? in

Her application ! | ! zd Structure Name Anaphytical data

What | II m was discovered in order to mm! calculated - 5255

X-ray NMR (400

Mha OM8O-o 8) mouth odt-05Z(2H).

Le 062-068 (28), ve M-cyclopropyl-4-1843-fluoro- 214-817 (ZNU, za these points, 4-methylbenzig)8-(33Z-triftbr 231 0 (Nu

TU not propyl)aminonmidazog! 2-Bipyridase Fe (NU, also in-z-ipr2-methylbenzamide | 2.80 (1); 3.53

Be Snu 389 (2NI, vo an), 7.08:ni, 7.13 (NI, 718-792 (IN), 7.30 (B), 7.47 (143, 7.82-7.99

IZ), 827) nshsh sh

Application | . :

Structure Name. Analytical data from

VT Aa Mu

Detected - 734 MU calculated - TROUBLE

IN-NMR (400

MGU OM5O-Я 6 я Thiryne ko 0.47-0.532Н), ше AB Brombentia 6ЧиЗ Я o.vo-o; 58 (NO, че -5-3-Bromobenzyl)-8-3 tri che fluoropropylaminoimidano no 0 shi se Vtorpropygaminoimidase 152-61 pi

And live и 258-270 (2), и и: in rydazine-Z3- . I still have methyl 2.vo (1n), 3.54 o with cyclopragyl- o methylpoenzam m: NI B (nu 43 dk Id 7 (Nu 0824

What is it? (IN) 71

CH, 7.36 (18), 7.3857.44 mon 453

BA V in 00785 (zn), 8.27 (1H)

Example 486

M-cyclopropyl-4-76-(3-fluorophenoxy)-8-((3,3,3-trifluoro-2-hydroxypropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y.2 -methylbenzamide

E school

E oo sosu and det eE de M

Oh dear

ZNM E he still

To the mixed solution 96 mg (200 μmol)

M-cyclopropyl-4-(6-(3-fluorophenoxy)-8-(methylsulfonyl)imidazo|1,2-5|Ipyridazin-3-yl|-2-methylbenzamide, which was obtained according to Intermediate Example 486ba, in 2 77.5 mg was added to ml of MMP

(0.6 mmol) of 3-amino-1,1,1-trifluoropropan-2-ol and 77.5 mg (0.6 mmol) of OIREA, and the mixture was heated at 160 C for 30 min. in a microwave oven. After processing and purification, 10.5 mg (9 95) of the title compound was obtained.

ORI O-M5: KT-1.23, MUM detected - 530.5, MMU calculated - 529.5)

Intermediate Example 48ba

M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-(methylsulfonyl)imidazo|1,2-b|pyridazine-

Z-yl|-2-methylbenzamide 87 ого 0.20 Ог82 он de» оон Shk Shoshey,

E om Kk Kk more om x O585o o585o oon oto o i Kk Kk o i,

To the mixed solution 4.96 g (11.06 mmol)

M-cyclopropyl-4-(6-(3-fluorophenoxy)-8-(methylsulfanyl)imidazo|1,2-5|Ipyridazin-3-yl|-2-methylbenzamide, which was obtained according to Intermediate Example 486p, in OME (250 mL) was added 20.4 g (33.18 mmol) of oxone in one portion at room temperature. After reacting for 72 hours, another 30 g (55 mmol) of oxone was added and the mixture was heated at 70 "C for one hour.

Extraction with ethyl acetate/water, filtration of the organic phase through a Whatman filter and evaporation of the organic phase gave crude product (4.96 g, 93 95) which was used without further purification. 1H-NMR (400 MHz, OM5O-ab), 6 IR - 0.44-0.50 (2H), 0.64 (2H), 2.73-2.82 (1H), 3.65 (ZH) , 7.19-7.24 (2H), 7.24-7.29 (1H), 7.39-7.45 (1H), 7.53-7.61 (2H), 7.68 (1H ), 7.72 (1H), 8.28 (1H), 8.37 (tn)

Intermediate Example 486

M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-(methylsulfanyl)imidazo|1,2-b|pyridazine-

3-yl|-2-methylbenzamide 87 ra 5

M

Vg M ГХ 5 Y

S E om -- z ih Zhe on ih

MN N

(c) M o u 8 G (19.2 mmol) of 4-(b-bromo-8-(methylsulfanyl)imidazo|1,2-B1 pyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, which was obtained according to the Interim

Example 486bs was converted similarly to Example 51, using 3-fluorophenol, obtaining after treatment and purification 4.96 g (46 95) of the title compound. 1H-NMR (400 MHz, OM5O-ab), 6 IR - 0.44-0.50 (2H), 0.60-0.67 (2H), 2.13 (ZN), 2.65 (ZN) , 2.76 (1Н), 6.99 (1Н), 7.15-7.25 (ЗН), 7.37 (1Н), 7.49-7.56 (1Н), 7.65 (1Н) , 7.73 (1H), 8.06 (1H), 8.24 zo (IN)

Intermediate Example 486c 4-(b-bromo-8-(methylsulfanyl)imidazo|1,2-b|pyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide in Ufa -ya - pi i O v

Wem | at 2-M

42.1 g (113.9 mmol) of 6-bromo-3-iodo-8-(methylsulfanyl)imidazo|(1,2-b|Ipyridazine, which was obtained according to Intermediate Example 486a, was converted analogously to Example Ta using M -cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) 5 benzamide, with obtaining after treatment and purification 17.78 g (34 95) of the specified in the title compound. 1H-NMR (300 MHz, OM5O-ab), 6 (ppr-: 0.47-0.53 (2H), 0.62-0.70 (2H), 2.36 (4H), 2.64 (ZH), 2.81 (1H), 7.19 (1H), 7.40 (1H), 7.86 (1H), 7.90 (1H), 8.12 (1H), 8 .91 (1H)

Intermediate Example 486a b6-bromo-3-iodo-8-(methylsulfanyl)imidazo|1,2-b|pyridazine

Vg v7

Ve ze t ma" Ve ny !!

To a stirred solution of 51.2 g (146.8 mmol) of 6,8-dibromo-3-iodoimidazo|1,2-b|Ipyridazine, which was obtained according to Intermediate Example 96c, in MMP (450 ml) was added 12.35 g (176.2 mmol) of sodium methanethiolate in one portion at 0" C. After reaction for 15 min., 700 mL of water was added and the precipitate was filtered off and dried. Trituration with ether, filtration and drying in vacuo gave 44.3 g (65 Fo) of the title compound 1H-NMR (400 MHz, OM5O-46), b (rrtui- 2.62 (4H), 7.15 (1H), 7.75 (1H)

The following examples of compounds were prepared analogously to the procedure described in Example 486 using the appropriate amine (LC-MS data such as retention time (CT in min) or mass peak observed were collected using LC-MS Method A unless otherwise noted)| :

The structure of Nazna | Analytical data of goth, sho (vto oi MU di V (Z:amine-3-I

Kk of ipuaminoi-in-(3-fluorine) was found in the eye, oxopropznaminoi b4Zeutorreno it 4 zhi PO 4895 MU eV and all sh SHE IN xy)imidazoi 1 2-vipridazin-z-ion that Is calculated

X IA M-cyclopropit2-methybenzam nei s 488.5 chuk 5 m i ! and and and ia sn BT: 088 MU

TK

! ro was discovered oh yet | WHAT 4896 MU 3 | t M-cyclopropyl-a-IZ-Pocdimethyla! schi that my ivminoi-v(3chr calculated the seam minosetiliamino m O-(Zrtorovnok

AUTO | whales Pe 54886 t silmidazo 1,2-pufidaziinnazialia»

And about iNMR (400 and Methylbenzamide not with- Mhn. MeO-

KO

/x bo roti: 0.45 (2H) 063

Tolya (FOR), 215 (68); veka ni 00275 i, 339 ! (2), 5 OB

IN, 7.09-7,119 (JAN), and well 0748 an tv p; 7.78 (Well 7.90 p, in in

With Tvteyat MM discovered that MA! calculated x HB per 1n-YAMe (300

MORE mgz om8o-a sovkkotaya 9 5 roti: "un Mecyclopragil i 83 rtorfenok o42-051 (ZNU avv also tp types of methyl. 1H-pyrazol- ZChl)m c5VOvV he ie svi" VE ethylpiaminoNmidase Z, 2-vipyridase Y

Same school | I 2143) 2.76 I veZ4Ali »-methyloenzamide and i | inU 00376 i (ZNU 445 2 NK 0ovoo pn" vyv (1), 708-726 (Well, and in, 00758 ipnUuU 0766

IN O0tovi

IN), 7.82 (an), 73-80 anquacin) and dt I LAMI found t 498.5 MM) calculated -897.5

Я1нН-ЯМе. (400

Ммга ом50-й и-х 6) Irrtie i 043-050), also M-cyclopropiv-4-6-(3-fluoropheno o5aovB (2). i or did 23 (ZN); 276 zvo i I as i e ( .

MORE n)-2-methylbenzamide Ш in Z that (well in 19 ше Ше ота ота что (4), 7.23 (No, 752-751

Sn), 755 (2. tl5 (NU, 75.87-7.95 (an), 7o5-805 an in on) vn shk ked "o and fa Sho VT 1.08 MU,

M Memikpopropyl-a-18-(3-fluorofenoc maya I o, revealed).

It is sy)-8-C13-(hydroxymethyl)oxevan-z. 4 lay rya pove a sho , y 5 88 Mu r -ip|metyp amino nmusazo 1 2-Vilry o: | | that it is calculated that rea dazin-Zip is mMethylbenzamide of it 55175 sh

CT 1.04 MU was detected (- 492.5 MU was calculated

AV

IN-YAMER (300

Mgts oMeO-a bo roti: vn 039-051 (2), vo I Tscho kutu 058-088 (2),

So KM-cyclopropyl-Yach (8-2, 3-dihydro | 2.14 (ZE, 2.76 t, pure PI cypropylamino!-b-(3-fluorophenoc (1)); 3.39 481 a propyl 1 b( 3-fluoro (1) db i)imidazoi 1,2-Zzpyridazine-Z- (38), 3.73 schi ilug-methylbenzamide pn ayu sha pn o"98 i" in o ovov (1), 702-720 (Z ), 720737

NOT 1-75 anu 7.86

Mon, 7.7V (p), 78 ni

Application Structure Name Analytical data

SHI tu - 128 MM detected sx 415.5 MA calculated 1 475.5 1n-nMR (400

MgGa ohm 65 Trotiv sm,

B 042:0.50 (NO, still . pav Z-second 080-0.67 (2),

I Chetsykpopil-a V (Zartorfeno What Sh i still emnorki 24 (ZN) 277

M I z-y xy)-8-((2-methoxyethylaminoimide 495 | here is what ynU 0326 kv azoi1,2-vipyridazinaa-

Ka I | (ZNU, Z and ipr2-methylbenzamide not o NE 353-358 m no, in zero lova (300725

IN 3-52 (en). 7.66 av

In, 7.82 n) me. with y

Her and KI

M-cyclopropip-4-I8-(IZ-(dimethyl KT 126 MU tk ie Kk mina)-3- was identified by:

That NI he that 493 p i in oxopregiliamino me (Z-frtorfeno 5150 MUH

M! and xiimidase 1.2-Vipridazine-z-ilya | the calculated ratio of -methylbenzamide is 51856

Like them

Application cStvusura Name "Analytical data

Eh, Eh! t

ИЙ | W 145 MM

Gay "Meadyclopropytchya Vch I I difluoro sh d. m . iamino)-8-(3-6 revealed x ju deya, cyclohexylmethyliamino)-5-(3-9 de LYA Y eutili BBOya MM pn torphenoxynmidazog,2-vipyridase oi zhkh | crein-3-epime-methylovenzamide in m I - 545.6 z i -X was calculated

That Tue 7 MM was detected w 488.5 MUU calculated 4875

Tsh-NMR (300

Мгц ОоМ85О-а 6). 5 (mercury

In 040-051 (NO,

In o 58-0892Н). m and Mecyclopropin-4-1843-fluoropheno | 0575-0891), same day. Sh : 495 I eyes xin a (ohegan-z-illeethylaminoim 12513 (38, 2578

SHY on idazogi, 2-vIniridazine-z-In), Z 81 ha! ! n pashk and | ip»2-methylbenzamide (Nu, and I AH - I vya sn» 463 2 Nu 00 biZ (nu), 7o5-7.20 (zn, 7.25

Nu 7-7 Va 18), 785 in, 75 (1NU, 785-756 (281 NO

SHCI pzhsh E ban

Monn KMcyclopropiv-4-8-3-fluoropheno | BT 1.03 MU g sho ksi VN. | discovered

Хов а І г: ши и ; 496 vet chori x tetrazole-yuchlmethylamino| | midazo | 500.5 MM and r P2-vipyridazine-Z- calculated not in it) -2-methylbenzamide 499.5

SD end she yan, ke «ky I KT 097 MY . Mcyclopropyl-4-18-412 (dimethinla pa: nie i | discovered x

And Ky mino)-2-methylpropylaminomach3-. 497 VO bu zhvU at 1. I SH 517 MM

Lech Fftrophenoxymidazoi 1,2 bipyride.

Co | | razine-Z-it-e-methypOenzamide was calculated. y "BIV k- t 3 a

M

577 sn sk from "DBN x o | | KT -o99 M "vn Macyclopropyl-a- 16 From fluorine substances A m | sho was found 1 pi syrn (a-methypomorpholineYaYa | I 498 | vyty schiny zro 00 MI rya propylaminoimidazoli 1,2-Bipyridase 3 also calculated ineZlIi-2-methypbenzamide not ; t BV i vi i5 se he, sh KT 098 MU shn Mecyclopropyl-ia-I16-(Z-fluorofenok as 00oddeekoyaM, kn, What org was discovered - sy)-8-12-(piperidine-1-ipetilyami 459 vyazak u in SH. 5U b MU and nonmidazo 12 v|pyridazine zli" a | calculated

DN metypbenzamide that her -528.6 more of them

Yam |. 0/5 g of M-cyclopropyl-a-(6--fluorophenoxy) was found in VT "003 MU) of 0/5 g. BOy r yutkdrivuinoY Z | | I 5, MM rya nonimidazo 12-1 pyridazine yana: « and calculated and metypbenzamide:;

AND

NO X n 5306 ay u

Ge u chic, shk still si, and . KT 096 Mocyclopropyl-I8-(3-fluorofenoc p an uv-pocha . vip) was detected

Eat cheese 8-2 (a-matilriregahin-1-uuet

B Sh crust and 544.6 MM roitaminoimidazoi 2 pyridazine-

KO , I calculated p Zli»-methylbenzamide nE and in x BAZ in Me i

My

H 1

M vn Y Kt 096 MM and M-cycloprogyl-a-16-(3-fluorofenoc with Seya-yo iniropidin-i itetinovn were detected and Ky syr 8-P2-(pyrrolidin-1-1 lzetitamin) was not excluded. 4 of 156 MU

X-x onmidazo1,2-viliridazine- with ite-a | calculated

AI methylbenzamide

EV d-N --O 5 1 46 i M ikh bot i eh sht Y 7

ШЧЧ ЧЧ I | CT 1.17 MA with Kecyclopropyl-ia-16-3 fluorofenok and uv-isimethytinet bamoyg) was detected -- and up to 0 db blue 3-Hmethylimethylcarbamoy! vases 1 J . | 68 we in amino)propylamivy midazeg and 2-811 b g calculated 54 iridazine-Zchili-2-methylbenzamide

E x 5456 pen and z

M r

Application | Structure І Name Analytical data: mon and pi in schi In.

How m. p tu - lo MU! in 4-I18-42-acetylamino)ethylaminoi obey, vis F u : M 2, the same substance I was also found: "Zartorfenoximidazogy 2551pi Y I nn | | 5035 MU with ridazin-a or M-cycloprogpip-2-me "Z Y | calculated and tipbendamide I not | I love them

I'm sorry

KI re

As ! | ВТ я 101 MU - M cyclopropyl-4-16-43-fluorophenokin in the group of tagdprogiai was found hot ty sy) a-413-(piperidin-t luprapilia !

BOB shi: U, What 85436 0 MA gray eye minonmidazoi and. 2-bipyridazinoYayaYal | s rya And ! calculated: and 2-methylbenzamide Sh

KE "54

NO I I s

With | tu - 0965 MU chok M-cyclopropyl-a-B- 3 fluorophenoch t 8-i34 folin-a-yl)ni and i niyavpeno - p plete, sy)-vaAD3-(morphoelin-4-1lp)propipia ! ve SOS is the cause of our) new m minonimidazo 1,2-BitridazineZ-(pyr

Her"

NT .x: 0.98 MU detected - 529 6 which is calculated x 528.6 ! ! 1n-nMR 1300

MHz MBO 6 Trrtiv in 0.43-0.50 (2), which OBO BT (YAN),

With 188(4H), 178. zm M-cyclopropyl-4-I6-3-fluorovenoc (hn) хи ! and in these VAZ (pyrrolidine-z il) propitam 507 hundred Y . | | | (ZN); 28-25 inoimidazo!1.2-ripyridazine-Zll|-g | shi

Ba | (NM v, ha "methypbenzamide v v (NYA), Za v NU voi, e i - in tov : shk

SAN), 7.2З (1); 742-752

IN 7 Watt

YN), TV (ST), 782-792 (2), B 17-B p st, probably

First 15 MM "mn KMecyclopropyl-4-16-(3-thorene and se ni somy cm syn 8-C3-(methylulfonigopropyl)

BOV OO) wine Y PI vav mu! and in aminonimidase 1,2-bipyridazine-z-il ku | More | 1 2-methyldenzamide of it in shk 537.6 b was also calculated

Re about VAT

With OVT 2 MYH mn AB DZ acetylamino propygamine x C same uv-3-fluorph of the native vyavlyenO x! п сх оч фортофеноксевимидазо| Teh 5OV Koko and IY vii MU me a: M Biniridazin-z-yl1-M-cyclopropini-ya ku and also calculated -methypbOenzamide "B166

And what are they?

VT 1.26 MM was found to be 432.5 MU, calculated -831.5

IN-nMR (300

Ministry of Local Government

Vb, BO Irotiv dk ve 040-052 (NI, vn, M-cyclopropyl-4-(8-3-frtorfenok 055750,73 (OH), 510 is i sy" (methylaminonmidase, 2-5) 220 (ZNiu

M zh I shk ne veridazine-Znt 2 methyloenzamide 29:82 PNI,

M 2.90(3H), 5558

NU, yo (ZN). 7.24 and), 741-7.55

IN), 7.59-7.73 (2), 7.76

IN 7.90 anna

Come on Structure Name Analytical data

M

In san Mecyclopropyl-4-IV-(Z-torfenok | VT i 110 MAU so shk st-8-o-Y H- | detected

IN: they are in the same place. ;

BO | here is teatrazol-v-itethylaminoimidazoi 5145 MM! Also 1,2-O-Ipyridazin-Z-yl 2-methylbenz | calculated leu 435 nen amide T-v13.5 al lk y

Bk K |. more V e 128 MY ri ee 1 Madyclopropyl-4-184(9,2-difluoro | discovered sch o i typ)aminoi-8-(3-Fluorophenoxy)mid | AV? In MM ko azo1,2-vilividazinez- and not yet calculated There is also 2-methylbenzamide and "815

Their

Ours:

N Y N and 1 | IvI-089MUu., themes of Muacyclopropyl-4-8-TA-Idimethyl y rapeny, mina)butylaminov-(Z-fluorophenopy vis | LY Do yY write and 5176 00 MU she a y |: ximidazog y2-Vipyridazin-3- and

DK in | calculated /

KA - metypovnzamid n y y x 516.65 x days

CT 2 1.06 MUU

NOT

! It was discovered that the art of war | | 505 MU to Sk Mecyclopropyl-ia-46-3-fluorophen

OZ 2 ze x 5 rcalculated ev, VES braids) 8-22 2-trifluoroethylaminoiy What

Fight her sh M u I i 2 vi : y - ach came to life with midaz 1. 2501pyridazin-z» i | NMR (400 units of ipu-2-methylbenzamide at a-iv MHz pM50-a at

M 8) Irrtie 043-051 (2),

Application |Structure Name MAnaphytical data 0.59-0.69 (2), 2.14 (ZN), 272-281 (1), 5.2O (NO; 6.96

CH), 7.157 (NO, 739 (NO 754 and, 7.67

PN) tA (1), 817 1), 8.25 (In) ha

X CT: 129 MUU of he and M-cyclopropyl-ab-3-brothorene were detected - pt sla ; ! y - sia 15th | g and ? | si) H-pyrazole-t-methylami |. 512.6 Let him rule! and noamidazoi 1,2-Viptridazine-z-ithie-| calculated

F | methylovenzamide Sv on and and

Example 516

M-cyclopropyl-4-I6-(2,3-difluorophenoxy)-8-2-(methylsulfonyl)ethyl|amino)imidazo|(1,2-b|Ipyridazin-3-yl|-2-methylbenzamide St. more / ; Z v y chn E sh o -M E M

UF / Su S /

Vg M z o zmin schi no E

N

/y M E n 9) id o M y M 147 MG (300 МКМОЛ) 4-(6-bromo-8-C2-(methylsulfonyl)ethyl|amino)imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 516ba was converted similarly to Example 51, using 2,3-difluorophenol, obtaining after treatment and purification 38 mg (21 95) of the title compound.

ORI C-M5: KET-1.14, MUM detected - 542.6, MM calculated - 541.6

Intermediate Example 516ba 4-(6-bromo-8-C2-(methylsulfonyl)ethylamino)imidazo(1,2-b|pyridazin-3-yl)-

M-cyclopropyl-2-methylbenzamide о тв (c) о и шк МН se se se se ОМ (9) и

Vg M N.M with OM

Vg M 6 - (v

X-MN I (o) XM o u

To the stirred solution, 1.12 g (2.5 mmol) of 4-Ib-bromo-8-(methylsulfonyl)imidazo|1,2-b|Ipyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, which was obtained according to with Intermediate Example 5160, 924 mg (7.5 mmol) of 2-(methylsulfonyl)ethanamine and 1.94 g (15 mmol) of OPIREA were added to 15 ml of MMP and the mixture was heated at 160 "C for 4 hours in a heater. After treatment and without further purification, 1.18 g (96 95) of the title compound was obtained.

ORI C-M5: ET-0.95, MUM detected - 493.4, MM calculated - 492.4

Intermediate Example 5165 4-(b-bromo-8-(methylsulfonyl)imidazo|1,2-b|pyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide v7 0.1.

M

Fa o. o osv on ac ve zm / o Zo: o o Y s s Kk Vg M

Жоо оо 0.20 87 с871 7 ЛооН о оо оо цо и Кк Кк о и. 12 G (28.8 mmol) 4-(β6-bromo-8-(methylsulfanyl)imidazo

P,2-5-Ipyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 4860 was converted similarly to Intermediate Example 486ba, obtaining after treatment and purification 8.61 g (59 95) of the title compound.

ORI C-M5: KT-0.98, MUM detected - 450.4, MM calculated - 449.4

The following examples of compounds were prepared analogously to the procedure described in Example 516 using the appropriate phenol or aniline (LC-MS data such as retention time (QT in min) or mass peak observed were collected using LC-MS Method A until otherwise indicated|:

her

I Mecyclopropyl-y-(vch(5-

And did the cat have fluoride? We have 2-methylphenoxy)-Yacho-(Me | found - 538.8 sia, h typsulfonygetitamine | MUU calculated -: pak and midazoi 1,2-vipividazin-3-y | 5376 in li-g-methypbenzamide

AI | t tue - 133 MM detected - 5546

MUM calculated - 5536 1n-nMR (300 cmt OhM5Ov

I ssh Micycloproviyev (3» ote 04351 i. -e Zh fluor-en). ovo (zn) tv What ee, 4-methoxyphenoxy)-8-012- | 912 (ZN) 2 in, and methylulsphoniethymami 3.05 (ZN), 349 (2, ! pe noimidazog1,2-Bipyridazine | 373-381 (2H), 3.84 same "B-ip|i-2methypbaenzamide (ZN) , 6:13 IN), 7.07 and t Sleep 717 IN), 7-2 Well; 730

NU tav-tva (2n),. 7.77 In), 782 In). in2ogNI

Application "structure Name

VT 42 MM was detected - 554.5

MUU is calculated from

WITHOUT

1H-YAMe (500 se V Y a y | Mgz OMBSnavB » 8 Mecyclopropylaya-ya» y Irrtit 0 049-053 sv o 4 M fluorine. i h u et z 5 vchy | (2NU, 0.660571. (28), and A I 4-methoxyphenoxy)8-19-Y What lot 213 (zn 281 18

E ko metypsulfonitet lam SCHE i in | | Z NO 358 (2),

And nonmidasa! 2 binvydazin oh! and not a-y Y 3.52 (OH), Veg5 (1H), c: "Zhn-2-methylbenzamide; sho ikh be AK IN), 71ach1NU 7.38 (Well, 765 (1) 7579

SNU lion (well, 826 in)

Example 520 4-[8-K2-amino-2-methylpropyl]amino|-6-(3,4-difluorophenoxy)imidazoi|1,2-BI5pyridazin-3-yl)yl]-N-cyclopropyl-2-methylbenzamide

MN not Mn,

MN t

MN

M

Ole, where is he?

M and I - M

Vg M E E o M no she

IS

N

2 o. )h o. 78 mg (171 μmol) of 4-38-(2-amino-2-methylpropyl)amino|-6-bromoimidazo|(1,2-b|pyridazin-3-yl)y"N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 520a, was converted analogously to Example 51 using 2,3-difluorophenol to give after treatment and purification 8 mg (8 95) of the title compound.

ORI C-M5: KT-0.97 MUM detected - 507.5 MUM calculated - 506.5

Intermediate Example 520a 4-[8-K2-amino-2-methylpropyl]amino|-6-Bromimidazo|1,2-b|Ipyridazin-3-yl-

M-cyclopropyl-2-methylbenzamide

Mn, oo t in MN - Y vek Nam vbsm/ / y tya E ikh shchi o. ii and 449 mg (1 mmol) of 4-I(Ib-bromo-8-(methylsulfonyl)imidazo|1,2-b|Ipyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, which was obtained according to the Intermediate Example 5166, converted similarly to Intermediate

Example 516ba, using 2-methylpropane-1,2-diamine, to obtain after treatment and purification 395 mg (86 95) of the title compound.

ORI O-M5: KET-0.75, MMUMU found - 458.4, MMU calculated - 457.4. 1H-NMR (300 MHz, rm50-ab6), 6 (rrit- 0.46-0.53 (2H), 0.62-0.69 (2H), 1.07 (6H), 2.35 (ZH ), 2.80 (1H), 3.16 (2H), 6.50 (1H), 7.36 (1H), 7.85 (1H), 7.91 (1H), 7.93-7 .96 (1H), 8.29 (1H)

The following examples of compounds were prepared analogously to the procedure described in Example 520 using the appropriate phenol or aniline (LC-MS data such as retention time (QT in min) or mass peak observed were collected using LC-MS Method A unless indicated other|:

Prikyo | Structure Name Analytical data Tue - 007 MM detected from: BOB

And MM is calculated -B5OBO ish-YAMe (300.

Mha IOM 5O-06); no, 'roti'

Sn a-O-Co-amino-e-methyliropi 3 044-052 (9),

Cereal amino|Y-6-(4-chlorophenoxyx 059-068 (H),

I. I and I Yu; - ; here are about 4 midasoi! 2-bipyridazin-3- 112 (c) 24 rosi I: i ri | ylMcyclopropyl-o-methylb (3), 2577 ИН) n.s.

Their | INu Titov (zn) 734 ch

TABL (NO 7vo-tvv (H), 7.74 in, your pnuvozinu VT oh 078 Mu and revealed 475.5

N

MUU is calculated nev, | - 4 no. ! ! yin-yaMe (300

Book 48 (2-amino-2-methylarogy

And I can OMBO-av), pc OH: aminoY-b-(pyridine-Z-ylokoy and

M. ZK to Y | , with. and ' Troote 522 pi Zimidazo| 1,2-vipyridazine-Z- o | Oiso85Oo (OH),

Zh / pumecikpopropyl-?-methylb sho naya pvo-ovya en), he | vnzamid 8 This | 114 (in) 212 schools (ZNU 278 (H)

And E

330 (3). 627 in tla an 740 In), tv.

What YN" t75B-7va (Well TV (YN),

TVA IN), and Mon You in 849 (IN), ! 8.57 (1)

Example 523 4-I6-(4-chlorophenoxy)-8-C2-(dimethylamino)ethylamino)imidazoi|1,2-BI pyridazin-3-yl|-I-cyclopropyl-2-methylbenzamide tupu

МН МН se SI se web" that, change Si -- -

What are we?

What nH c) in 07 and 68 mg (150 μMOL) 4-(6-bromo-8-2-(dimethylamino)ethyl|amino)imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 523a was converted analogously to Example 51, using 4-chlorophenol, to obtain after processing and purification 20 mg (27 95) of the title compound.

ORI O-M5: KT-0.97, MMU detected - 506.0, MMU calculated - 505.0. 1LN-NMR (300 MHz, rm50-ab6), b (rrity) - 0.47 (2H), 0.59-0.68 (2H), 2.12 (ZH), 2.18 (6H), 2 .52 (2H), 2.76 (1H), 3.39 (2H), 6.06 (1H), 7.13-7.25 (2H), 7.27-7.35 (2H), 7 ,46-7.54 (2H), 7.63 (1H), 7.72 (1H), 7.90 (1H), 8.22 (1H)

Intermediate Example 523Za 4-(6-bromo-8-C2-(dimethylamino)ethyl|amino)imidazo(1,2-5|Ipyridazin-3Z-yl)-

M-cyclopropyl-2-methylbenzamide 02 in МН щ щ with M Я M y

Vg M stat Vg M i n o. qi o. and their their 449 MG (1 mmol) 4-(b-bromo-8-(methylsulfonyl)imidazo

P,2-5-Ipyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 51606, converted similarly to Intermediate Example 516ba, using M,

M-dimethylethane-1,2-diamine, with treatment and purification yielding 367 mg (80 95) of the title compound.

ORI C-M5: CT-0.70, MUM detected - 458.4, MUM calculated - 457.4. 1H-NMR (300 MHz, rm5090-ab), b Irrtu- 0.50 (2H), 0.65 (2H), 2.17 (6H), 2.35 (ZH), 2.51 (2H), 2.80 (1H), 3.39 (2H), 6.38 (1H), 7.36 (1H), 7.44-7.50 (1H), 7.84 (1H), 7.91 ( 1H), 7.94 (1H), 8.28 (IN)

The following examples of compounds were prepared analogously to the procedure described in Example 523 using the appropriate phenol or aniline (LC-MS data such as retention time (QT in min) or mass peak observed were collected using LC-MS Method A unless indicated other|: tue - 074 Mu sv, Revealed t 4725 em

KI MUU is calculated

M is M-cyclopropyl-4-IV-Ch2-(dimethyl 14715 what else is laminoethylamino»B-(pyridine-a | NAM? (300

Oh houses of thorns and ; about zypoxy) imidazo I, 2-Bipyridazine- MG OMBOavu. NO 3-1|-2-methylbenzamide рр 0 043-0.50: shi ogni) 00859067 ее (nu 22 (B)

And 2.20 (BNO, 2.49-2.59 zatv in tiZz wn), ! | tav VM 7 (IN), 7-7

ВН» 768 (1Н) 7,ВО1Н),; 788-799 anu 82 IN), 89541), 8557 (IN)

Ak nd sh ke . with - ik and her in M-cyclopropyl-yabZ and difluoro | ME with 095 MM go | and i in: phenoxy)-8-(2-(dimethylaminates and found xx 507.5

B io! ше тп ше What and dec titaminoimidazoi 1.2-Vipiridase | MUM is calculated - also I n in-z-yl e-methylbenzamide 596.5

And I AK sho

Their

Example 526

M-cyclopropyl-4-I6-(2,3-difluorophenoxy)-8-((1-methylpiperidin-4-yl)methyl amino)imidazo(1,2-b|Ipyridazin-3-yl|-2-methylbenzamide o

MN no dom sl

OM Y -- IA. with M and : we E about M but E E

IS

N

THYROID: THYROID: 90 mg (181 μmol) 4-(6-bromo-8-1(1-methylpiperidin-4-yl)umethylamino)imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 526ba was converted analogously to Example 51, using 2,3-difluorophenol, obtaining after treatment and purification 16 mg (15 95) of the title compound.

ORI bO-M5: KT-0.97, MMU detected - 547.6, MUM calculated - 546.6. TN-NMR (300 MHz, rm50-ab6), b IRrt)- 0.41-0.52 (2H), 0.58-0.69 (2H), 1.20 (2H), 1.67 (ZH ), 1.80 (2H), 2.11 (6H), 10. 2.67-2.82 (ZH), 3.22 (2H), 6.16 (1H), 6.69-6.81 (1H), 7.13 (1H), 7.26-7.34 (2H), 7.42 (1H), 7.59 (1H), 7.67 (1H), 7.79 (1H), 7.92 (1H), 8.22 (1H).

Intermediate Example 526ba 4-(6-bromo-8-C1-methylpiperidin-4-yl)umethylamino)imidazo|1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide n 02 i zv

VI zm Y On se - -klkh6 -- as - Y - VG M

MN

(in)

And"; She

M

449 mg (1 mmol) of 4-(b-bromo-8-(methylsulfonyl)imidazo|1,2-B1 pyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, which was obtained according to the Intermediate

Example 516p was converted similarly to Intermediate Example 516ba, using 1-(1-methylpiperidin-4-yl)umethanamine, to obtain after processing and purification 460 mg (92,965) of the title compound.

ORI O-M5: KET-0.76, MMUU detected - 498.5, MMU calculated - 497.5. 1LN-NMR (300 MHz, rm50-ab6), 6 (rrit- 0.46-0.53 (2H), 0.61-0.70 (2H), 1.18 (2H), 1.53-1 .68 (ZN), 1.75 (2H), 2.08 (ZN), 2.34 (ZN), 2.63-2.76 (2H), 2.80 (1H), 3.18 (2H ), 6.38 (1H), 7.36 (1H), 7.84 (1H), 7.87-7.98 (ZH), 8.28 (PN)

The following examples of compounds were prepared analogously to the procedure described in Example 526 using the appropriate phenol or aniline (LC-MS data such as retention time (QT in min) or mass peak observed were collected using LC-MS Method A unless otherwise noted |: zo

adverb;

Structure Name Anaphytical data order

WHAT W i ol We discovered 519.6 MUU calculated - 511.6 1H-YMe (300

EMmMGa MOU t. m Grrgiie 0.43-0.50(2H), i OBO (28). 1,211

M-cyclopropyl-2-methyl-a(a) and she kn I (2), 157 (Z), 1.85 1, "CY methyphnperidine nim. Gas, I (2, 212 (ZH), LA wide ch ky etypiaminomo-(lyridin-Zal Sho Shcho sta (3H3. 270-281 (ZN),

Mbxy)midazo(2-bipyridase 0000. I x y Sh y Z (2) You IN), va NA ilibenzamide I ponty z about TZ in I Well

TV 75-72 ON) tv tk ny I ZY TYA 77-83 n 790

PNU 815-853 (TTN),

VAV VIN)

Example 528

M-cyclopropyl-4-16-(2,3-difluorophenoxy)-8-(methylamino)imidazo|1,2-B)pyridazin-3-yl|-2-methylbenzamide

MN

E Mn

M u/Fe and Fu web" - M

Oh yes

80 mg (200 μmol) of 4-Ib-bromo-8-(methylamino)imidazo|1,2-5|Ipyridazin-3-yl|-Y-cyclopropyl-2-methylbenzamide , which was obtained according to Intermediate Example 528a, was converted analogously to Example 51, using 2,3-difluorophenol, obtaining after treatment and purification 18 mg (14 95) of the title compound.

ORI C-M5: KT-1.27, MUM detected - 450.5, MUM calculated - 449.

Intermediate Example 528a 4-(b-bromo-8-(methylamino)imidazo(1,2-5|Ipyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide

(in)

From Mn

Fe Fe - Y web" / web

MAN and

N

/ L 1123 mg (2.5 mmol) of 4-(β6-bromo-8-(methylsulfonyl)imidazo|1,2-Bpyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, which was obtained according to the Intermediate

Example 516p was converted similarly to Intermediate Example 516ba, using methanamine to obtain after processing and purification 1000 mg (100 95) of the title compound.

ORI C-M5: ET-1.08, MUM detected - 401.3, MU calculated - 400.3.

The following examples of compounds were prepared analogously to the procedure described in Example 528 using the appropriate phenol or aniline (LC-MS data such as retention time (QT in min) or mass peak observed were collected using LC-MS Method A unless indicated other):

And Pryakl. | Strysura Nazhe 00000000 |Anapitichdan i vo I Y | and I other and more Czech M-cyclopropyl-4-(O-(X,

PI I what! in in a4difluorophenoxina CT oh 127 Mu

In: YOU pe methylamino)midazoi!, | found x 450.5 MUU of AH in 2-VIpyridazinyl M) calculated x 449.5 and Methylbenzamide

IPrykyut Structure of Nazza Analytical data

I B Kcyclopropyl-4-185(5-

Se, fluor- ozh olvtsi and 2 There is in VT 8 1: Mu! and -methylphenoxy)-v(m I

BO zu, m revealed - 448.5 MU

Ma ethylamino)imidazoga- And not . And calculated - 445.5 and oh Vipyridazine: Evil 2-meth m and !

Her" ildenzamid

VT i 097 MM detected - 443.5 MUM calculated x 4428

TEYAMe sh00

Mgz OM5Oo-a6b) o" pav (rhiue 0.51-0.56 (2H). as M-cyclopropyl-2-meth | | What

І with C OBO 70 (24), 756 ps nny p-ia-8-(methylamineoya)

Y A o I 33, 2.81 (ZN 2.83

Mod, rve 2-(methylamino)phenoco " ich sche p YN) zga (38, 516 her, "mschimidazog ee ovshtiridase sho o x yn-Zhypibenzamid y2 695 (2). 715-723 2), 7.33 (1H) , 7.85 well, about anu) 8? mn) tuyu M-cyclopropyl-4 (B-(2

And with Iosh "droxypheniimethytl VT 5 001951 MY

Goly din I I

Hi her and, h. Substitute B-(methypamino) | found x 443.5 MU 5 | HE Ya shi What is imidazo Me b|ipiridase | calculated - 442.5

It's not her fault. ! their ita-methylpbenzamide

Application |Structurase Name | Analytical days

Not another 7

Bonn p g shk, M "NYKA 9 pr 9 pi 46 Y ts5

Cat -"fluoropyridine-Ziyuoyyu | WTO 1050 M 533 E U y|-8-imethypaminoimide | found x 433.5 MA:

ІІ As K t " zogy,2-vipyridazine-Z- | calculated t 435.5 a X ipuo-methylbenzamide lys | tia

Z t M-cyclopropyl-4-16-(8-vv r nd 0231 rt fluorine. t DY : anna nn | | KT ego zi-4 0 MU

I: and A. 4-Methoxyphenoxy)-in-( 54 І not; what was found x 402.5 MUU of methypaminonimidazolii, and I also calculated x 461.5. what is 2-vipyridazineZaliom their ethibenzamide

VT ох 123 МЙ detected х- 402.5 M calculated - 461.5 т1Н-яЯМе 00

MG MB, o»: Shk M-cycloprogyl-4-46-43- ) рр: 0.44-0.50(2Н), seni shk SHY ay a fluor-OvI-ov7 (28), 22

K i di M

This is 4-methoxyphenoxyme-| (38) 274-281 (1), 535 of the Code of Criminal Procedure

Zh metypaminoimidazoi, 290 (38), 3.84 (ZN), ih MAY x

THAT vipyridazine-zilosm | B! (IN), 703-708 their ethylbenzamide an. la an), taya (Nu. 725

ON, 781 (Nu 765 inU and (nn), 789

OH) in (tn)

Example 536

M-cyclopropyl-4-I6-(2,3-difluorophenoxy)-8-D2-(morpholin-4-yl)ethyl|amino)imidazo|(1,2-b|Ipyridazin-3-yl|-2-methylbenzamide

977 9773 in va

MN E MN

Fe -- SOK

M. Y

Vg M no, oh we

IS

H H c) I He) I 100 MG (200 μmol) 4-(6-bromo-8-C2-(morpholin-4-yl)ethyl|amino)imidazo

P,2-5Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 53ba was converted analogously to Example 51, using 2,3-difluorophenol, obtaining after treatment and purification 25 mg (21 95) of the title compound.

ORI O-M5: AT-0.93, MUM detected - 549.6, MUM calculated - 548.6. LN-NMR (400 MHz, rm50-av6), 6 (rrite- 0.44-0.50 (2H), 0.60-0.67 (2H), 2.11 (ZH), 2.46 (4H ), 2.61 (2H), 2.77 (1H), 3.46 (2H), 3.57 (4H), 6.17 (1H), 7.14 (1H), 7.27-7, 34 (2H), 7.39-7.46 (2H), 7.59 (1H), 7.67 (1H), 7.93 (1H), 8.11 (1H), 8.23 (IN)

Intermediate Example 53ba 4-(6-bromo-8-C2-(morpholin-4-yl)ethylamino)imidazo(1,2-b|pyridazin-3-yl)-

M-Cyclopropyl-2-methylbenzamide

1123 mg (2.5 mmol) of 4-I(Ib-bromo-8-(methylsulfonyl)imidazo|1,2-b| Ipyridazin-3-yl|-N-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 5166, was converted similarly to Intermediate

Example 516ba, using 2-(morpholin-4-yl)uthanamine, to obtain after processing and purification 1360 mg (108 95) of the title compound.

ORI O-M5: VT-0.74, MUM detected - 500.4, MUM calculated - 499.4.

The following examples of compounds were prepared analogously to the procedure described in Example 536 using the appropriate phenol or aniline (LC-MS data such as retention time (QT in min) or mass peak observed were collected using LC-MS Method A unless otherwise noted |:

tu-0.95 MU detected - 545.6 MU calculated - 544.6 1H-NMR at (300 MHz,

F. rm5901-a6), b i (rrti- 0.44-0.51

E MH (2H), 0.60-0.67

Fo M-cyclopropyl-4-(6-(5-fluoro- (2n), 2,11 (6H), and 2-methylphenoxy)-8- 2,40-2,49 (4H), 537 om" / Ceg -(morpholin-4-yl)ethyl|amino)imidazo | 2.59 (2H), 2.77

Sn P,2-5|Ipyridazine- (1 H), 3.38-3.49

Y 3-yl|-2-methylbenzamide (2n), 3.53-3.60 ns (4H), 6.09 (1H), with n 7.06 (1H), o M 7.11-7.20 (2H), 7.27 (1H), 7.32-7.39 (1H), 7.58-7.64 (1H), 7.71 (1H), 7.91 (1), 8.20 (IN) (c) in pl. вт-0.85 МУ r. М M-cyclopropyl-2-methyl-4-(6-(2-(meth identified - Щ lamino)phenoxy)|-8- 5А? in MM 538 about us" Ce-(morpholine -4-yl)ethyl|amino)imidazo is protected - but (1,2-bipyridazin-3-yl) B in

CH benzamide ' n.s N

SHI tu-0.81 MU detected - 542.6 MU calculated - 541.6 1IN-NMR

C (300 MHz, not SOSIZ), b (rrti-

I" M-cyclopropyl-4-(6-((2-hydroxyphenyl) 0.70 (2H), 0.89 on K and (2H), 2.38 (7H),

C /Fe (methyl)amino1|-8- 2.52 (2H), 2.98 539 mi" Ce-(morpholin-4-yl)ethyl|amino)imidazo (ZH) C 30 (2n) vn, P, 2-B|Ipyridazin-3-yl)- 37 ( 4) Bean and 2-methylbenzamide (1H), 5.92 (1H),

CI 6.42 (1H),

M 6.89-6.99 (1H), 7.10 (2H), 7.22 (ZH), 7.65 (1H), 7.78 (1H), 7.90 (tn)

Structure (c) c

E MN

E p.

F xy)-8- detected - 540 Ohm Ce-(morpholin-4-yl)ethyl|amino)imidazo 549.6 MUU

P,2-B|Ipyridazine- calculated -

3-yl|-2-methylbenzamide 548.6 ns n

M

SHI vtT-1.06 MU detected - 532.6 MU calculated - 531.6 IN-NMR (in; (300 MHz,

F. rm5o-a6), b i (rrti- 0.44-0.52

E MH (2H), 0.59-0.68 c r M M-cyclopropyl-4-(6-((5-fluoropyridine- (2H)), 2.14 (ZH), sth 3-yl)oxy|- 8- 2.39-2.44 (AN),

BA с l C2-(morpholin-4-yl)ethyl|amino)imidazo| 2.58 (2H),

P,2-Shipyridazine-3- 2.73-2.81 (1H), yl)y-2-methylbenzamide 3.45 (2H), not 3.51-3.59 (4H), with and 6.14 (1H), 7.17 o M (1H), 7.41 (1H), 7.59-7.64 (1H), 7.70 (1H), 7.91 (1H), 7.98 (1H ), 8.22 (1H), 8.50 (1H), 8.54 (IN)

Example 542 tert-butyl 3-I(((3-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-6-(3-fluorophenoxy)imidazo

P,2-Shipyridazine-8-ilyamino)methyl I|azetidine-1-carbosylate; and

My MN

MN

Fo te x MM ko om

Oh, oh

N. M. ich

To the mixed solution, 10 MG (21 μMOL) 4-8-Cazetidin-3-ylmethyl)amino|-6-(3-fluorophenoxy)imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl-2- of methylbenzamide, which was obtained according to Intermediate Example 542a, 1. mg (42 μmol) of formaldehyde, 44 mg (204 μmol) of sodium were added to 1 ml of OSE

Ihiacetoxybogopuagide apa 24 μl (411 μmol) NOAc at room temperature. After 72 hours, the mixture was worked up and purified to give 2 mg (18 95) of the title compound.

ORI O-M5: KT-0.93, MUU detected - 501.6, MMU calculated - 500.6. 1LN-NMR (300 MHz, rm50-ab6), 6 (rrit- 0.43-0.50 (2H), 0.59-0.67 (2H), 2.14 (ZN), 2.30 (ZN ), 2.77 (1H), 3.15 (ZH), 3.40 (2H), 3.51 (2H), 6.08 (1H), 7.07-7.19 (2H), 7, 24 (1H), 7.47 (1H), 7.66 (1H), 7.76 (1H), 7.82 (1H), 7.91 (IN), 8.18-8.26 (2H)

Intermediate Example 542a tert-butyl 3-I(((3-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-6-(3-fluorophenoxy)imidazo

P,2-Shipyridazine-8-ilyamino)methyl|azetidine-1-carbosylate 0.0 t M

M i t MN

MN se IH /Ffya /

DC of the 00s

Oh, oh

N M o I and id

To the mixed solution 43 mg (74 μMOL) tert-butyl 3-(((3-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-6-(3-fluorophenoxy)imidazo|1,2-5|Ipyridazine-8- yl)amino)methylI|azetidine-1-carbosylate, which was obtained according to Intermediate Example 5426, in 3 ml of OSM was added 1 ml of TREA and two drops of water at room temperature. After 1 hour, the mixture was worked up to give 34 mg (93 95) of the specified in the compound header.

ORI C-M5: ET-0.82, MUM detected - 487.5, MMM calculated - 486.5.

Intermediate Example 5425 tert-butyl-3-(((3-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-6-(3-fluorophenoxy)imidazo|1,2-b|pyridazin-8-ylamino)methyl|azetidine -1-carbosylate c) c) 5

NAM "about.150 s to" and lo

K; m še ob" / ra o iy u

M c) h b 192 MG (400 МКМОЛ)

M-cyclopropyl-4-(6-(3-fluorophenoxy)-8-(methylsulfonyl)imidazo|1,2-5|Ipyridazin-3-yl|-2-methylbenzamide, which was obtained according to Intermediate Example 48ba, was converted similarly

Example 486, using tert-butyl 3-(aminomethyl)azetidine-1-carbosylate, yielding after treatment and purification 43 mg (18 95) of the title compound.

ORI C-M5: AT-1.36, MUM detected - 587.7, MUM calculated - 586.7.

Example 543

M-cyclopropyl-4-I6-(2,3-difluorophenoxy)-8-((1-methylazetidin-3-yl)methyl amino)imidazo(1,2-b|Ipyridazin-3-yl|-2-methylbenzamide

N. M

My MN

MN

DM co

THEIR CHA - EE region

Oh, oh

IS

IS

HM o U and id 10 MG (21 μmol) 4-i8-Cazetidin-3-ylmethyl)amino|-6-(2,3-difluorophenoxy)imidazo|1,2-b|pyridazin-3-yl)u" M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate Example 543a, was converted analogously to Example 542, obtaining after treatment and purification 0.8 mg (6 9) of the title compound.

ORI O-M5: VT-0.94, MMU found - 519.6, MUM calculated - 518.6.

Intermediate Example 543Za 4-8-Cazetidin-3-ylmethyl)amino|-6-(-2,3-difluorophenoxy)imidazo|1,2-b|pyridazin-

3-yl)uM-cyclopropyl-2-methylbenzamide 2.29 c and E MH

E MN E so that s: Ko i u pk zm o m'mi om n

N HM

97 in (c) and 120 MG (200 μmol) tert-butyl 3-(((3-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-6-(2,3-difluorophenoxy)imidazo|1,2-b |pyridazin-8-yl)iamino)methyl I|azetidine-1-carbosylate, which was obtained according to Intermediate Example 5436, was converted analogously to Intermediate Example 542a, obtaining after treatment and purification 13 mg (13 95) of the title compound.

ORI O-M5: KT-0.92, MMUU detected - 505.5, MMU calculated - 504.5. 1LN-NMR (400 MHz, rm50-av6), 6 Irrte 0.44-0.50 (2H), 0.60-0.68 (2H), 2.11 (ZH), 2.72-2.81 (1H), 3.08-3.18 (1H), 3.59 (2H), 3.66-3.74 (2H), 3.91 (2H), 6.26 (1H), 6.74 (2H), 6.93 (1H), 7.14 (1H), 7.26-7.34 (1H), 7.43 (1H), 7.59 (1H), 7.67 (1H), 7.94 (1H), 7.99 (1H), 8.21 (1H)

Intermediate Example 543p tert-butyl-3-(((3-(4-(cyclopropylcarbamoyl)-3-methylphenyl/|-6-(2,3-difluorophenoxy)imidazo|1,2-b|Ipyridazine-8-ilyamino) methyl|azetidine-1-carbosylate

Tell her MORE

MN E I dO eD-SK

OM / Zk - y

VM tro E obsm"

IS

N N

5, A, 195 MG (200 μmol) tert-butyl 3-((6-bromo-3-(4-(cyclopropylcarbamoyl)-3-methylphenylimidazo |(1,2-5|Ipyridazin-8-ilyamino)methylI|azetidine) - 1-carbosylate, which was obtained according to Intermediate Example 543c, was converted similarly to Example 51, using 2,3-difluorophenol, and the product was used without treatment in the next stage.

ORI S-M5: KT-0,1,37, MUU detected - 605.7, MU calculated - 605.7.

Intermediate Example 543c tert-butyl 3-((6-bromo-3-(4-(cyclopropylcarbamoyl)-3-methylphenylimidazo|(1,2-b|Ipyridazin-8-yl)amino)methylI|azetidin-1-carbosylate

M

0.0 NM (

Fe MN - Y

Vg m" de - M -- as M ny M Vgm pr o. In 1348 MG (3 mmol) 4-(b-bromo-8-(methylsulfonyl)imidazo

P,2-5-Ipyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 516ba was converted similarly to Example 516, obtaining after treatment and purification 1.67 g (100 95) of the compound indicated in the title.

ORI C-M5: KET-1.28, MUM detected - 556.5, MMM calculated - 555.5

Example 544 4- and 8-Casetidin-3-ylmethyl)amino|-6-((5-fluoropyridin-3-yl)ioxy|imidazo

P,2-Shipyridazin-3-yl)y-N-cyclopropyl-2-methylbenzamide c); in); that!

M

M her yo E MN

E MN

"shtsoshe" -x a.

M 5 MY bot / pelvis

N

N HM

And o u c); iy

MG (8 μmol) tert-butyl 3-(((3-(4-(cyclopropylcarbamoyl)-3-methylphenyl)-6-K5-fluoropyridin-3-yl)oxy|imidazo|1,2-B|Ipyridazine-8 -ylamino)methylI|azetidine-1-carbosylate, which was obtained according to Intermediate Example 544a, was converted similarly to Intermediate 5 of Example 542a, obtaining after treatment and purification 3.7 mg (99 95) of the title compound.

CT-0.80, MMU found - 488.5, MUM calculated - 487.5. IN-NMR (300 MHz, OM5O-46), b

IR - 0.43-0.51 (2H), 0.59-0.69 (2H), 2.15 (ЗН), 2.77 (1Н), 3.17 (1Н), 3.59 (2Н ), 3.73-3.85 (2H), 3.92-4.04 (2H), 6.21-6.26 (1H), 7.17 (1H), 7.64 (1H), 7 .70 (1H), 7.73 (1H), 7.92-8.01 (2H), 8.20 (1H), 8.33 (1H), 8.39 (1H), 8.55 (1H ).

Intermediate Example 544a tert-butyl 3-I(((3-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-6-(5-fluoropyridin-3-yl)oxy imidazo|1,2-b|pyridazine-8- ilyamino)methyl|azetidine-1-carbosylate

To) oo ry mi iy i

MN E E MN o y i - what tire o weight" m. | Mal on

N r

SHI: 111 mg (200 μmol) tert-butyl 3-(6-bromo-3-(4-(cyclopropylcarbamoyl)-3-methylphenyl)imidazo|1,2-b|pyridazin-8-ilyamino)dimethyliazetidine-1- carboxylate, which was obtained according to

Intermediate Example 543c, converted similarly to Example 51, using

B-fluoropyridin-3-ol, yielding after treatment and purification 5 mg (4 95) of the title compound.

ORI C-M5: ET-1.25, MUM detected - 588.7, MMM calculated - 587.7.

Example 545 4-8-Cazetidin-3-ylmethyl)amino|-6-(5-fluoro-2-methylphenoxy)imidazo

N,2-N-pyridazin-3-yl)-N-cyclopropyl-2-methylbenzamide

Zoo in); in); to me!

M

My E MN

E MN de» M I - M y

OM and shi (6) M in); M

H x-K / o u o id 120 mg (200 μmol) tert-butyl 3-(3-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-6-(5-fluoro-2-methylphenoxy)imidazo|1, 2-5|Ipyridazine-8-ylamino)methyl I|azetidine-1-carbosylate, which was obtained according to Intermediate Example 545a, was converted analogously to Intermediate 5 of Example 542a, obtaining after treatment and purification 13 mg (13 95) of the title compound.

ORI S-M5: KT-0.94 MUM detected - 501.6 MUM calculated - 500.6

Intermediate Example 545a tert-butyl 3-I(((3-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-6-(5-fluoro-2-methylphenoxy)imidazo|1,2-b|pyridazine-8-ilyamino )umethyliazetidine carbosylate in re m m s E E E de de em web / - t zm i on om

H H also "X 111 mg (200 μmol) tert-butyl 3-(6-bromo-3-(4-(cyclopropylcarbamoyl)-3-methylphenyl)imidazo|1,2-b|pyridazin-8-ilyamino)dimethyliazetidine- 1-carbosylate, which was obtained according to

Intermediate Example 543c was converted similarly to Example 51, using 2,3-difluorophenol, and the product was used without treatment at the next stage.

ORI S-M5: KT-0,1,43, MUU detected - 601.7, MU calculated - 600.7.

Example 546 4- and 8-K(3-aminopropyl)amino|-6-(3-fluorophenoxy)imidazo|1,2-b|pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamido ry o knshchi and MH

MN M

8 -- their de Fe

HER E os" /

E yszostyu" p

H 2-K (c) with 23 mg (40 μmol) tert-butyl

I3-(3-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-6-(33-fluorophenoxy)imidazo|1,2-b|Ipyridazin-8-yl)iamino)propyl|carbamate, which was obtained according to the Intermediate Example 546a, was converted analogously to Intermediate Example 542a, obtaining after treatment and purification 7 mg (36 95) of the title compound.

ORI O-M5: KT-0.94, MMUMU detected - 475.5, MMU calculated - 474.5. 1LN-NMR (300 MHz, rm50-ab6), 6 (rrite 0.43-0.51 (2H), 0.59-0.68 (2H), 1.81-1.97 (2H), 2, 14 (ЗН), 2.76 (1Н), 2.87 (2Н), 3.41 (2Н), 6.14 (1Н), 7.08-7.19 (4Н), 7.19-7, 28 (1H), 7.49 (1H), 7.60-7.73 (ZH), 7.73-7.82 (2H), 7.93 (1H), 8.21 (1H)

Intermediate Example 546ba

M-cyclopropyl-4-/6-(3-fluorophenoxy)-8-((3,3,3-trifluoro-2-hydroxypropyl)amino imidazo|1,2-b|Ipyridazin-3-yl)y-2- methylbenzamide o also oo and 8

M MN

-WHAT -

IH ufya / Ho in Fe

E (6) M ry - M y o MN ME o she ia

Mn, 7 MN H (c)

M in 67 mg (140 μmol) of M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-(methylsulfonyl)imidazo|1,2-b|pyridazin-3-yl|-2-methylbenzamide, which was obtained according to Intermediate Example 486ba was converted similarly to Example 486, obtaining after processing and purification 23 mg (29 Fo) of the title compound.

ORI O-M5: ET-1.38, MUM detected - 575.7, MMM calculated - 574.7.

Example 547 3-(13-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-6-(3-fluorophenoxy)imidazo

P,2-B|Ipyridazin-8-ylamino)propane-1-sulfonic acid and 9

Another o-5-OH

MN E Z

-8K -- /Fe d in FU

And: | 101 mg (200 μmol) 3-((16-bromo-3-(4-(cyclopropylcarbamoyl)-3-methylphenylimidazo)

P,2-VIpyridazine-8-ylamino)propane-1-sulfonic acid, which was obtained according to Intermediate

Example 547a was converted similarly to Example 51 to obtain after treatment and purification 12 mg (9 95) of the title compound.

ORI O-M5: KT-0.98, MUU found - 540.6, MMU calculated - 539.6. 1H-NMR (300 MHz, rm50-av6), 6 IR 0.40-0.54 (2H), 0.58-0.70 (2H), 1.81-1.99 (2H), 2.14 (ZN), 2.49-2.62 (2H), 2.77 (IN), 3.46 (2H), 6.29 (1H), 7.11-7.21 (ZN), 7.27 (1H), 7.42-7.55 (1H), 7.64 (2H), 7.74 (2H), 8.11 (1H), 8.22 (1H)

Intermediate Example 547a 3-(16-bromo-3-(4-(cyclopropylcarbamoyl)-3-methylphenylimidazo|1,2-b|pyridazine-8-ilyamino)propane-1-sulfonic acid (in o-5-OH 02. and 5 MN

Fe Fe with M Y c) y

Ve M Ha Ve zm i in XX MN, on

N

M. N

(c) M 97 y

To the mixed solution of 41 mg (300 μmol) of 3-aminopropane-1-sulfonic acid in 2 ml

24 mg (600 μmol) of sodium hydride was added to OM5O at room temperature. After 30 min, 90 mg (200 μmol) of 4-(β6-bromo-8-(methylsulfonyl)imidazoi|1,2-Bpyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, which was prepared according to Intermediate

Example 516B, with the receipt after stirring for 2 hours of the crude title compound, which was used after evaporation of the solvent without further treatment.

ORI C-M5: ET-0.82, MUM detected - 509.4, MM calculated - 508.4.

Example 548 2-(13-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-6-(3-fluorophenoxy)imidazo

P,2-B|Ipyridazine-8-illiamino)ethanesulfonic acid

ZOZ g 2 ov 0-8 no 1 no i

MN E MN se S Fo a M - y

Vg Mominshchino E

N

07 u o i, 99 mg o (200 μmol) 2-(6-bromo-3-(4-(cyclopropylcarbamoyl)-3-methylphenylimidazo)

P,2-VIpyridazin-8-ylamino)ethanesulfonic acid, which was obtained according to Intermediate

Example 548a was converted similarly to Example 51, obtaining after processing and purification 9 mg (7 95) of the title compound.

ORI O-M5: KET-0.97, MMUMU found - 526.6, MMU calculated - 525.6. 1LN-NMR (400 MHz, rm50-ab6), 6 (rrite 0.44-0.54 (2H), 0.59-0.70 (2H), 2.14 (ZH), 2.71-2, 84 (ЗН), 3.59 (2Н), 6.22 (1Н), 7.09-7.21 (4Н), 7.27 (1Н), 7.49 (1Н), 7.61-7, 67 (1H), 7.73 (2H), 8.12 (1H), 8.23 (IN)

Intermediate Example 548a 2-(6-bromo-3-(4-(cyclopropylcarbamoyl)-3-methylphenylimidazo|1,2-b|pyridazine-8-ilyamino)ethanesulfonic acid o / 09. ю

From MN

Phew Phew

M and GF) and

ВМ хх вбосм 5 МН и шеш 2 -- -ж он - у о7 ий 89 MG (200 МКМОЛ) 4-(b-bromo-8-(methylsulfonyl)imidazo|1,2-B1 pyridazin-3-yl| -M-cyclopropyl-2-methylbenzamide, which was obtained according to Intermediate

Example 5160 was converted similarly to Example 547a to obtain the crude compound specified in the title, which was used at the next stage without further purification.

ORI C-M5: ET-0.84, MUM detected - 495.4, MM calculated - 494 4.

Example 549

M-(1-cyanocyclopropyl)-4-16-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)-2-methylbenzamide

IS

E eE Ii U

IN

MN

MN - M

In 2-8 zu, .M y 5 M y -- OM om uv d

E about 10.5 mg (22 μmol) 4-16-(3-fluorophenoxy)-8-I((3,3,3-trifluoropropyl)amino|imidazo

P,2-S-pyridazin-3-yl-2-methylbenzoic acid, which was obtained according to Intermediate Example 459a, was converted analogously to Example 459, using 1-cyanocyclopropanaminium chloride, obtaining after treatment and purification 4.5 mg (36 95) indicated in the title of the compound.

1H-NMR (0M50-α6): 6- 1.21 (2H), 1.50 (2H), 2.16 (ZH), 2.61-2.76 (2H), 3.60 (2H), 6.14 (1H), 7.14 (2H), 7.25 (2H), 7.49 (1H), 7.66-7.76 (2H), 7.81 (1H), 7.97 ( 1H), 9.09 (1H) ppt.

Example 550 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazin-3-yl)y-2-methylbenzamide (A) and 4 -(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazin-3-yl)y.2-methylbenzoic acid (B)

IS

In U

MN

M MN MN o) s o o --- I Y that g. Y om om

Y M v F v F (c) ih on, o7Ton

And in

A mixture containing 50 MG (97 µMOL)

M-cyclopropyl-4-76-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide and 0, 5 ml of hydrobromic acid, heated at 120 "C for 10 min. under microwave irradiation. Water was added, the precipitate was filtered and purified by chromatography to give 30.0 mg (62 95) of the title compound A and 4.1 mg (9 Fo) of the title compound B. 1H-NMR (0M50-a6) A: 6- 2.20 (3H), 2.68 (2H), 3.60 (2H), 6.13 (1H), 7, 13 (2H), 7.22-7.30 (ZN), 7.48 (1H), 7.60-7.78 (AN), 7.93 (1H) mp 1H-NMR (0M5O-46) B: 6- 2.35 (ZH), 2.68 (2H), 3.59 (2H), 6.15 (1H), 7.14 (2H), 7.26 (1H), 7.49 ( 1 H), 7.64-7.77 (HN), 7.82 (1H), 7.99 (1H), 8.20 (1H) ppt.

Example 551 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)-M, 2-dimethylbenzamide g in .

In U

MN MN

/F Fe o zm u - » o zi Y d to. o. o

A mixture containing 30 mg (63 μmol) of 4-16-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl-2- methylbenzoic acid, which was obtained according to

Example 550, 2.94 mg of methanamine, 36.1 mg of M-Kdimethylamino)(ZH-(1,2,3|)griazolo|4,5-B pyridin-3-yloxy)methylene|-M-methylmethanaminium hexafluorophosphate, 11 ,6 MG M,

M-dimethylpyridin-4-amine and 1.5 mL of M,M-dimethylformamide were stirred at 23 °C overnight. The solvent was removed and the residue was purified by chromatography to give 30.0 mg (92 95) of the title compound. 1H-NMR (0М50О-авб): 6- 2.16 (ЗН), 2.49-2.76 (2Н), 2.69 (ЗН), 3.60 (2Н), 6.13 (1Н), 7.13 (2H), 7.20 (1H), 7.25 (1H), 7.48 (1H), 7.63-7.74 (2H), 7.76 (1H), 7.93 (1H), 8.08 (1H) ppt.

Example 552

M-ethyl-4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazin-3-yl)-2-methylbenzamide and c.

In U

MN MN

Fe Pho obbny Y - vkh om J g du oon sy 30 mg (63 μmol) 4-16-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino) imidazo|1,2-b|pyridazine -3-yl/y.2-methylbenzoic acid, which was obtained according to Example 550, was converted analogously to Example 2 using ethanamine to give after treatment and purification 29.7 mg (89 95) of the title compound. 1H-NMR (0M5O-ab): b- 1.06 (ZH), 2.16 (ZH), 2.68 (2H), 3.19 (2H), 3.60 (2H), 6.13 ( 1H), 7.13 (2H), 7.19 (1H), 7.25 (1H), 7.48 (1H), 7.64-7.74 (2H), 7.76 (1H), 7 .93 (1H), 8.15 (1H) ppt.

Example 553 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazin-3-yl/-M-isopropyl-2-methylbenzamide)

E in AND

Re

MN MN and ek) se z. .M-Y --- oz ob d E Ch oon (c) X- 30 MG (63 μmol) 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazin-3-yl)y-2-methylbenzoic acid, which was obtained according to Example 550, was converted similarly to Example 2, using propan-2-amine, obtaining after treatment and purification 13.4 mg (39 95) of the title compound. 1H-NMR (0M50-a6): b- 1.09 (6H), 2.14 (ZH), 2.68 (2H), 3.60 (2H), 3.99 (1H), 6.13 ( 1H), 7.08-7.19 (ZH), 7.26 (1H), 7.48 (1H), 7.66 (1H), 7.72 (1H), 7.77 (1H), 7 .92 (1H), 8.03 (1H) ppt.

Example 554 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazin-3-yl/-2-methyl-M-(3, 3,3-trifluoropropyl)benzamide

IS

IS

Her U

In MN

MN se o 2 2, ,M i

D-t om u still /is E AR

E oi o7Ton 11.8 MG (25 μmol) 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo)

P,2-S-pyridazin-3-yl)y-2-methylbenzoic acid, which was obtained according to Example 550, was converted analogously to Example 2, using 3,3,3-trifluoropropan-1-amine, to give after treatment and purification 12, 0 mg (83 95) of the title compound. 1H-NMR (SOSIS): b- 2.34 (ZH), 2.41-2.65 (4H), 3.69 (4H), 5.90 (1H), 5.97 (2H), 6, 94-7.08 (ZH), 7.28 (1H), 7.39 (1H), 7.65 (1H), 7.75 (1H), 7.77 (1H) ppt.

Example 555 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazin-3-yl)y.-2-methyl-M-( 2,2,3,3,3-pentafluoropropyl)benzamide v. and U

In MN

МН se 2-2 with ММ /Фы / - about M is d

E o" oon a;

E and E 11.8 mg (25 μmol) 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo)

The p,2-pyridazin-3-yl)y-2-methylbenzoic acid obtained according to Example 550 was converted analogously to Example 552, using 2,2,3,3,3-pentafluoropropan-1-amine, to give after working up and purification of 12.5 mg (82 95) of the title compound. 1H-NMR (SOSIS): b- 2.34 (ZH), 2.50-2.65 (2H), 3.69 (2H), 4.16 (2H), 5.91 (1H), 5, 96 (2H), 6.93-7.08 (ZH), 7.32 (1H), 7.40 (1H), 7.67 (1H), 7.76 (1H), 7.80 (1H) ppt

Example 556

M-(2,2-difluoroethyl)-4-16-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)y- 2-methylbenzamide

IS

E and sa

E and i

MN DM se /Fi y 5 I-Y --k om om yu I still I,

E obTon o - 11.8 MG (25 μmol) 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo)

P,2-Pyridazin-3-yl)y-2-methylbenzoic acid, which was obtained according to Example 550, was converted analogously to Example 551 using 2,2-diphthopentanamine, obtaining after treatment and purification 13.4 mg (93 95) of the title compound. 1H-NMR (SOSIS): b- 2.35 (ZH), 2.58 (2H), 3.69 (2H), 3.82 (2H), 5.90 (1H), 5.93-6, 02 (2H), 5.99 (1H) 6.95-7.08 (ZH), 7.33 (1H), 7.40 (1H), 7.66 (1H), 7.76 (1H), 7.79 (1H) ppt.

Example 557 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-BI pyridazin-3-yl/-N-isobutyl-2-methylbenzamide)

IS

Oh and sa

And in

МН se хх MY -- ом ом ве ев, о он - 11.8 MG (25 μmol) 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo)

The p,2-pyridazin-3-yl)y-2-methylbenzoic acid, which was obtained according to Example 550, was converted similarly to Example 551 using 2-methylpropan-1-amine, obtaining after treatment and purification 12.8 mg (96 95 ) of the title compound. 1H-NMR (SOSIS): 6- 0.99 (6H), 1.89 (1H), 2.35 (ZH), 2.58 (2H), 3.28 (2H), 3.68 (2H) , 5.74 (1H), 5.89 (1H), 5.97 (1H), 6.92-7.08 (ZH), 7.30 (1H), 7.39 (1H), 7.64 (1H), 7.74 (1H), 7.76 (1H) ppt.

Example 558 4-(6-(4-chlorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazoi|1,2-BI pyridazin-3-ylIII-M, 2-dimethylbenzamide and

In the RU

MN chn oz oz o o o N

SI o7Ton SI o M 25 MG (5 µmol) 4-16-(4-chlorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazin-3-yl-2-methylbenzoic acid, which was obtained according to Intermediate Example 556a, was converted similarly to Example 551, obtaining after treatment and purification 11.1 mg (43 Fo) of the title compound. 1H-NMR (0М50О-авб): 6- 2.15 (ЗН), 2.61-2.75 (2Н), 2.70 (ЗН), 3.60 (2Н), 6.13 (1Н), 7.21 (1H), 7.32 (2H), 7.51 (2H), 7.64 (1H), 7.69 (1H), 7.74 (1H), 7.93 (1H), 8 .09 (1H) ppt.

Intermediate Example 55va 4-(6-(4-chlorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)y2-methylbenzoic acid

IS

E E

In Ry

IS

MN

M MN uF / se o -» x MM ohm u M o shchi o M s obton

A mixture containing 00 MG (566 μMOL) 4-(6-(4-chlorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)"M -cyclopropyl-2-methylbenzamide and 13.4 ml of hydrobromic acid, heated at 1207 for 2.5 days. Water was added, the precipitate was filtered to give the crude title compound, which was used without further purification.

Example 559 4-(6-(4-chlorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazoi|1,2-BI pyridazin-3-yl)y-N-ethyl-2-methylbenzamide

E E

E E

In U

MN chn

Fo u obi o o o M

SI on SI o she

MG (51 μmol) 4-(6-(4-chlorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo)

P,2-S-Pyridazine-3-yl-2-methylbenzoic acid, which was obtained according to Intermediate Example 55va, was converted analogously to Example 2 using ethanamine to give, after work-up and purification, 10.4 mg (37 95) of the title compound. 25 1H-NMR (0M5O-avb): 0-1.07 (ZH), 2.14 (ZH), 2.62-2.75 (2H), 3.20 (2H), 3.60 (2H) , 6.13 (1H), 7.20 (1H), 7.32 (2H), 7.51 (2H), 7.64 (1H), 7.69 (1H), 7.74 (1H), 7.93 (1H), 8.15 (1H) ppt.

Example 560 4-(6-(2-fluoro-4-hydroxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo

P,2-5-Ipyridazin-3-ylHy-M, 2-dimethylbenzamide

Zo8 g g.

In R

MN MN

Fo Fo o Bi Y -- o from 7

IS . Kk F

N on o on on Ho) M 12.8 mg (26 μmol) 4-16-(2-fluoro-4-hydroxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo

P,2-Shipyridazin-3-yl-2-methylbenzoic acid, which was obtained according to Intermediate Example 560a, was converted similarly to Example 551, obtaining after treatment and purification 5.6 mg (43 Fo) of the title compound. 1H-NMR (0М50О-авб): 6- 2.15 (ЗН), 2.61-2.79 (2Н), 2.70 (ЗН), 3.60 (2Н), 6.13 (1Н), 6.64 (1H), 6.73 (1H), 7.13-7.25 (2H), 7.58-7.70 (2H), 7.75 (1H), 7.93 (IN), 8.09 (1H), 9.87 (1H) ppt.

Example 560ba 4-(6-(2-fluoro-4-hydroxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-B1 pyridazin-3-yl-2-methylbenzoic acid)

IS

R more

RU

MN

M MN fiya / se o -- with MM

E | ohm

IS

M 9 (c) - (6) I» on o on 75 mg (13v8μmol) M-cyclopropyl-4-(6-(2-fluoro-4-methoxyphenoxy)-8-((3,3,3-trifluoropropyl) amino|imidazo|1,2-b|Ipyridazin-3-yl-2-methylbenzamide was converted similarly to Intermediate

Example 558a, with the receipt after treatment of 76.6 mg of the title compound with a purity of 85 95, which was used without further purification.

Example 561

M-ethyl-4-16-(2-fluoro-4-hydroxyphenoxy)-8-((3,3,3-trifluoropropyl)amino imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide

And in

In U

MN MN fe Fe lake 65207 lake

E Go F

N on oon on o Kch 12.8 MG (26 μMOL) 4-16-(2-fluoro-4-hydroxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b| Ipyridazin-3-yl-2-methylbenzoic acid, which was obtained according to

Intermediate Example 56b0a was converted analogously to Example 551, using ethanamine, to obtain after treatment and purification 9.6 mg (713 95) of the title compound. 1H-NMR (0M5O-46): b- 1.07 (ZH), 2.15 (ZH), 2.68 (2H), 3.20 (2H), 3.60 (2H), 6.13 ( 1H), 6.64 (1), 6.74 (1H), 7.14-7.23 (2H), 7.60-7.70 (2H), 7.75 (1H), 7.92 ( 1H), 8.16 (1H), 9.86 (1H) ppt.

Example 562 4-I6-(3,4-difluorophenoxy)-8-C2-(morpholin-4-yl)ethyl|amino)imidazo

P,2-5-Ipyridazin-3-yl|-M, 2-dimethylbenzamide

(c) 077

With c

And MN se se vet / ob ( sn, IF SN»

IS

(c) but also Me sleep,

To a stirred solution of 48 mg (1200 μmol) of sodium hydride in 1.2 ml of OM5O, 156 mg (1200 μmol) of 3,4-difluorophenol was added in one portion at room temperature. One hour later, 95 mg (200 μmol) of 4-(6-bromo-8-Ce-(morpholin-4-yl/ethylamino)imidazo|(1,2-b|Ipyridazin-3-yl)-M, 2-dimethylbenzamide , which was obtained according to Intermediate Example 562a, was added to 1 ml of HOM5O, and the mixture was heated for 8 hours at 140 "С in a microwave oven. After processing and purification, 7.42 mg (7 95) of the title compound was obtained.

ORI O-M5: KET-0.82, MUU found - 523.5, MMU calculated - 522.5. LN-NMR (300 MHz, rm50-a6), 6 (rrite 2.16 (ZH), 2.45-2.47 (ZH), 2.59 (2H), 2.67-2.75 (4H) , 3.44 (2H), 3.53-3.60 (4H), 6.07 (1H), 7.12-7.19 (1H), 7.22 (1H), 7.91 (1H) , 7.47-7.60 (2H), 7.66 (1H), 7.74 (1H), 7.91 (1H), 8.09 (H).

Intermediate Example 562a 4-(6-bromo-8-C2-(morpholin-4-yl)ethyl|iamino)imidazo|1,2-5|Ipyridazin-3Z-yl)-

M, 2-dimethylbenzamide (c)

WITH

Ve I to Ve zn ( sn, (c) ni sn,

1.94 g (15 mmol)

OSIREA and 1.30 g (10 mmol) of 2-(morpholin-4-yl)uthanamine in one portion at room temperature. After heating for 2 hours at 70 "C, 100 ml of OSM was added and the mixture was washed with water (3 x 100 ml). The organic phase was dried over sodium sulfate and evaporated to give a brown solid, which was used without further purification in the next step. To the stirred of a solution of the remaining solid in 20 ml of TNE was added 1.16 g (6 mmol) |3-methyl-4-(methylcarbamoyl/uphenyl|Iboronic acid, which was obtained according to Intermediate Example 56260, 15 ml of an aqueous solution of potassium carbonate (15 mmol, 1M), 816 mg of Ra(arroSi" (1 mmol), and the mixture was heated for 41 hours at 70 "C, obtaining after treatment and purification 2.35 g (99 95) of the title compound.

ORI O-M5: KET-0.71, MUU found - 474.4, MMU calculated - 473.4. 1LN-NMR (400 MHz, rm50-a6), b (ppm- 2.37 (ZH), 2.42 (AN), 2.54 (2H), 2.73 (ZH), 3.26 (2H) , 3.49-3.59 (AN), 6.42 (1H), 7.40 (2H), 7.56-7.63 (1H), 7.86 (1H), 7.92 (1H) , 7.96 (1H), 8.18 (IN)

Intermediate Example 562

13-methyl-4-(methylcarbamoyl)phenyl|boronic acid 6) in o

M -Zhh s still t he

To a stirred solution of 20.22 g (67 mmol) of M-cyclopropyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-daoxaborolan-2-yl/benzamide in acetone (300 ml ) added 43.08 g (201 mmol) of sodium periodate, 134 ml of acetate (134 mmol, 1 M in water), and the mixture was stirred for 3 hours at room temperature and 2 hours at 40 °C. 4 M NaCl (32 ml) was added and the organic phase was removed in vacuo The mixture was extracted with ethyl acetate and the organic phase was washed with water, dried and removed in vacuo to give 14.59 g (94.2 95) of the title compound.

1H-NMR (400 MGu, OM5O-ab6), 6 Irrtu- 0.44-0.52 (2H), 0.59-0.67 (2H), 2.26 (ZH), 2.78 (1H) , 7.18 (1H), 7.53-7.61 (2H), 8.01 (2H), 8.19 (1H).

The following example compounds were prepared analogously to the procedure described above in Example 562 using the appropriate intermediate compound and the appropriate phenol I|LC-MS data such as retention time (CT in min) or mass peak observed were collected using LC-MS

Method A, unless otherwise noted):

shouts The structure of the sinus and: seh KT ho oo

NI, I ba M.2-dimethyl-4-46-02- MU

IR of methylphenocoi)-8-12" revealed - morpholine" BO, MU and shko МН и х хо "ilietipivminomidazoi!,2. And calculated

My Seh I | and iv. her C sleep, "Vipridazinud- - OO V da ipibenzamid Her nk

SE, nn vn |. nnia ra g it, "va. tto otv i m methoxyphenoxy)y-2- | MU dya and vd Y che (morpholine-Y- was detected by se om reiluethylivminomidase.2 51765 00 MM. sty "b Х tt. - і іІ і schy om | -vitridazin-Z-p im 2- calculated

EE M sia not dimethypbenzamide 5 that s y i y 44642-fluoro-a- KT o 08 nn methoxyphenoxy)8-2- Mu vve sho. (morpholine-I" was discovered --

In I oh "and and . oh . I

AN and ip)ethylaminoimidazoY1,2 535,5 MU,

E. February 7: ; and Usrya -Viptiridazine-Z-17l1-M,9- was calculated

Makh s v zo dimethypbenzamide k- BA sv, ni sne

She Av5-fluoro-o- MI ho 0.84 m mn methylphenoxy» 8-12. M vv sho. | (morpholine-y" revealed 5 different sl; these are ip)ethylaminonimidazoi 1,2 | 51956 MM

But, pol y Z y t. y shi nn ie, -Vipyridazin-Z-iyaYarM- 00) was calculated by Shchya and in kadimatibenzamid x 515.8 h.

G.! St.

Prikp,. Structure Name D|Analytic data i liviZA- dto- o. vv difluorophenoxy)-8- MM vvi EI Art. Ktetrahydro-oNi-pyran-Y- | found -- nim raipmethyl)aminoimidazoii, 508.5 MM

He svn, 2-Bipuidazin-Z-il).M» | dimethylbenzamide was also calculated - 5078 tons of current drinking water

MIH

! found aa MU. calculated -k 4858 1H-yaMe: (300

Mgts OoM8o-. 46). Grotiv bu tlialdoshchi M. ε-dimethyp-4-1O-(2- (Z); 85 tav methylpphenoxy)-B- NU 186.

OM, Y Ctetrapdro-oN-piran-y- | 2.03 (8),

BV) oo ylmethylamine imidazoi, 2.50. (vn) sp, ! Jan iv pluamino copper; and ii 1).

Mo en, 2-bipyridazine-Z- 2,88 (ZN), that ilibenzamide 322 (Nu. schv, zaz en) von), 743 a, and Bto3

NU 0728. 728 IN), 783 (B) 7.51-7 85 no 785 shi what | Mon | T.v5

IynNuU 0 voB) sn y tt A A 02020200 Sh v s s A-- Z-fluorosrenoxy)-ya- «nn (5-(Z3krtorf ) Mu

I eat it Ktetrapydro-en-pyran-i- !

OO | shi o revealed hi 568 and yumetitamino mylazogi. | and x. 400.5. WE! m from Bprdidazine ZALMONY | dimethylbenzamide was calculated

Аа -488 5 вк св, ох, и и з р d-(в-(4- KT A 15 1. as Y cm that methoxyphenokoi)-8- MUU in si So Ctetrandro-2H-pyranei- revealed si ! not ipmethyliaminoimidazoi!, 150285 MU (and also Fn, 2 v|pridazin-Z- it was calculated that cha dimethylbenzamide - 5016 sn, ele pi | |! SHHI

E | ha 4 / i ze 4-85 2-fluoro-a- VT o-19 sn, "vv methoxyphenocosy)-v- MUU

Olek, WE : . what! | OO In Ktetraidro-eni-piran-Ya: discovered - 71 ia! in ipmetyp)aminoiminazoi, 5206 MU! and M and V i h. shchen, 2-viviridazin-Z-ili-M2- | calculated in dimethylbenzamide I 5196 no sn,

Structure Name Analytical data on . What else? | ! ny 4-BAbrtora tu xx 124

Kk dn methylphenaoxy)-8- MUU in tve, Itetrapdro-2iCh-piban-Y- | it was found in r: no ipmethyptaminoimidazoii, | 5046 MM shen, 2-Vipridazine-3-l'Ma- calculated in which dimethylbenzamide - BO sn, and 4-55 3-fluoro-ja- KE c- and c. km methoxyphenoxyЯ- MUU!

Kolya and it; . - the narrowness of the topic Ctetrahydro-2H-pyran-i-| It was found out that it was in the SM and that it was from ipmethyliaminonmidazoi, | 520.6 MUU shi ton, 2-Vipyridazin-3-i»M.2- | calculated: cha dimethylbenzamide 56 not sn

And ha and min shi

DY a4-(6B-(34- ! I still Shchi and and in tu 1.29 lin difluorophenoxy) B»

From Mu pu CZ 33" that Vo u as

Ot Y dazog,2-Bipyridazine-3- : se | calculated

IM a- I

Hey and | 505.4

Kk dimethylbenzamide

KT ho 129 syu MU

OM! And not that 4-53 btorphenoxy) I | revealed about: and I, (3.33-4885 M kosh О.В, and trifluoropropyl)aminoyimi | calculated

TB g still ze i, fluorine Ro ) 1 develop dazo!i,2-B|Ipyridazine-3- | -487.8; that ildchma" 1IN-NMR. (300

BZ dimethybenzamide; Mgy OM5Oo- and 46), Irrachre 2.16 IZNI,

Application Structure Name | dkalitic data 2.59-2.76 (VNU ZB

UN Convention), visa inc. 13 (2) pt methoxypheniocom)-B"

Her Ii; Schi MUM in she CZ Y 57a san zy trifluoropropitaminoi mi pYiaELego Y "Kshchya o Zv viv MUM kish Y dazo! 1,2-vipyridazin-3- sn МН | | calculated im ah I i - 517.8

MORE Dimethypizenzamide. n

Yes, the author! ШЯ siv VT 182 in methyphenoxy)-8- iz M sv, zu 3.3, 3- M 577 yar trifluoropropyl)aminoi mi py : dor dk I ! 02.5 MUYE

Her dosage is vipridazine-Z-

VN | done! name" and

IS . - BO and dimethylbenzamide

Add.. (strkura Name. for a- in 3-fluoro-a-

MONA shchi! | . VT o- 0125

Shock methoxyfenokoi)B-, "Sh. | MUU ri 3.33. 78 Concrete Ff spdaminoimi | discovered - towers and SI YOU: trifluoropropiaminomi! and more; Ш Bi85 MM (8 ! dazo 1,2-ripyridazine-Z-

OM, sei calculated ' and M2-

Ed. and - 1 That is - dimethyloenzamide

She and I. and. AB i» VT 117 and She s and vok Km difluoroethylaminoiY-in- MUU

Teh LLC; m I S KE (3 4- revealed oh ku ! volya these x and y: difluorophenoxy)kndazoi | 5744 Mu c di 1,2-vipyridazine-z-yl- calculated by M. 2-dimethybenzamide x 4734

BT - 116

We found lab We calculated -4855

Beck | TN-NMR (300 ! І 48-22»

And SN MN and YE MGTS MO.

Zk A m difluoroethyl)aminoiv-(2- pyny a o, 46) with (rot: also ad Y Ffluoro-a-

BNO father I 210 (Z),

Ema methoxyphenoxyimidazo x p 1 z ri Z u 2.7o (3,

PAN g Dpirvidazin-oziu

B I | Y. 378 (ZN). dom M.2-dimethylbenzamide and sia; Sat (ZNU 5.23 (MON), 832 PN, 584 YN) t05 t t YN tv mon a a p sun

Pryka Structure Name Analytical data 78в2 и в, 770-т78 и О007987 что 0808 и ! (But

AND

AI! ! | Art.

Ge and | Already 4 ke and 448-023. cha | MM sk | dipterphenoxy)-8-((2-

BV yin f | methoxyethylaminoimid. the alty of methoxystaminomid is m r | She 4685 MUH ota ion and zo11,2-Bipyridazin-zailu» no Y mn Av Sh | and calculated at xx | M.edymethylbenzamide and more! oh av75 we Y! seTAu

VTtoya about IV

FLY

I | revealed - ! | 468.5 MU! | "VV sn" was also released | Y, Z vo chn-YAMe (400 more | 4446-34 | Mch MBO- ob, difluorenoy)vn obu (here

I and - ;

Ba bl methoxyethylaminoimide 2,16 (ZNU,

In : g TU zogi, 2-v) tiridazin-zil 1270 ZN), in What | M 2-dimethyloenzamide 327 OH),

Kk vol

Tov, zva (en),

And call the call

In selected background (avu 722 (yN) 78 IN

Ex., |Structure | Name! 7.50-7 50 (NU 00766 in 075

In, 7-2

Mon), 8.09 Mon) Sun, ! "4842" Tue In other methoxyethylaminesv- MU! meatballs,

COME ON; i2- discovered -

BAZ nku shnya Zh and methylphenoxynimidazoi! 3 445.5 MUM and 2-vipyridazin-3-i1M,2- | 2 dimethylbenzamide x 4aB B was calculated! BM dream, dream gezhsch tuo 116 i av efftor-a: Mu : CHU drink methoxyphenoxy)-8-(2- svi! And schi was found 5 and Z84 for z methoxyethylaminethymide

A. av mm az E Zh. | zog1,2-bIpyridazinZ-iya- i zhk my YN | calculated

T zhd M. zhdimethypbenzamid that

I am yen, wm 419.5 sm, cm,

More | DTo- 100 kn a65rtorikh mm some metyphenaxivV- (a

Ok. it was found that he 58 au of methoxyethylaminoimide pk A her | y o ravav 0 MU ut oh oj y 3011,2-Vipyridazin-Z-il-ts as hi g y | it is calculated by | M, 2-dimethyloenzamide

Not x 463.5 sm,

Tricks Structure Name Analytical data of St. Fr.

And and | KT Otchan 446-(3-fluoro-methylmethoxyphenoxy)-8-2"

IN; CH 56 of alu methoxyethylaminoimide was found.

And their What Sh "v05 00 M

FO a zo 2vipyridazinedchuya

Ai he 7 , | calculated that M2-dimethyprenzamide was closed " sn, z

Mu was detected - 432.3 MA calculated - 451.5 14-NMR (400 imp OMVO-av). from Jerotiye St. 214 (H) and zva 789 (38). "un ay che zi 28 sko, methoxyethyl)aminoIb-

OS midazoi 2 (well for

I. 587 Ghana enoxymidase 1,2-

WRITE rya and zinM (2nu 353. sha: how. pyridazinez ili Me" What Y p shsh y y y 359 (ОН), х. dimethylbenzamide yet? вв 00 ИН) s and ! yap 78 00 a, 7-78 (НМ 738) (PN), 71. 7А8 (о H 7657 ИН), 1.75 ИН,

And! 7.81 IN Java (IN)

and Allah! - them - az NT 088

Ka | difluorophenoxy)-8-D2- | MU de bat M,

IR and y (morpholine-4- was detected (c:

BV from | that ra Х ip)ethylamino midazoY12 0 557.6 MA t U besv . And | ! you SHY "Vipyridazin-z M. calculated and no To ethyl-d-methybenzamide - 53658

U. on at kn more

І Methyp-?-methyl-a-|B-(2- KT with 088 also methylphenoxy)- 8-12» MU dikit y H and not K t. and not

Zoo (morpholine-Y" was dumped in the east

Va db pi no. CC of the yth ipietyliaminoimidazoi1,2 | 5156 0 MU

S se sne "pyridazine-z- calculated

Me I I nya 5 iprenzamide -5146 ne 7 ve M-ethyicha84(- VU x OV83 i. ii methoxyphenoxy)-8х12- | MUM for i M i py ri g - - . - oo imorphalin-ya- was found out in 590 and what else and a- ilethylaminoimidazog,? | 531.6 00 MU t 4 e-sn, shi: . I eat that and that

B well, 7 "pyridazines" have been calculated

N shi y o en, v y metypbenzamide "5308 y i ke : nn shin

Prica, Structure

BT - OV)

MU detected - 5 barks We calculated

Its "vav V nyam (300 . Mch oMBOo- or rr 1.96 (ZNU. 310 8, sk i i o M-ethyl-4-ib-2- fluorine 259 (Nu

K. methoxyphenoxy)-v4O VLA Ya

Sl | (morpholin-ya- | university

БВ І І Хо и ипетилиаминомимомидазой 2 | But with 53.

I and se fipridazine-Zilyo-050 (NU b st. o methybbenzamide 377 (ZN), ; that blo No 854 (IN) v.87-8 88

In); 7.05 mot?

IN Oto 732 In, 7.82 (PN); 77? Well 78 OO Nh Vanu

Attributes: Structure Name Analytical data a and s.

Eh shu y Y (morpholine-4-vyvvpena x 52 aby

Savy sia and others. - and and them, - St., "Viividazin-zeilie- calculated! I" methylpbenzamide tv not dto-oo

Mu was discovered

B MM calculated « 500.6 1n-jaMe. (400

MHz oM5O-s | ab). from the mouth"

S o tob OZ N

Ol Metygio-metyp-a-(Va» "vn that 214 (3) : (morpholin-Я- I ey . 258 2)

M sy ipzety p amino|-in- 53 so that | o Z (4H), approx. n-th phenexyimidazoY1,2- g U sn zaz (H)

Co as Eitridazine-Z-t Zeo | 5 (5), I 1pubenzamid ! !

Sh 6.05 (Nu. yo tato anu 7.26 (BI), 1-75 en 7.66

I), 7.75 ! In), 7.50 (8 visas

NO

Application It costs 0000000 | Name 0 danalytical data

VT zho 128

MM detected 522 0 MU

It is calculated - BIV 1nYAMe (300

Faculty of Higher Education and Higher Education, ab o rot 107. (ZNU

How | 11.32 va 44643A- (well what

Z, difluorophenoxy)-8- (2), 1.86 and rylmethytaminoimidazag!, in (ZE uch Chi st 2-vipyridazine-vilme | 314-3.5

E o o btyl-d-methylbenzamide /(BN)., 383 pe! | (NA 8509 inu Oy. 723 2), 748-750

NU 78 tav and 758-777 nu 7.90 sy, vyv in

CT medical lab

MUH detected - 486.5 MM calculated - 856 1H-yaMe (400

MHz OM5O- 45). i Irrtie 106 (ZI), 7 Z 115-129 t Methyl-2-methyl-d-(6- (4n), 1:82 nm phenoxy-8-(Ktetrahydro- | (2H), 1.85- g vych 2H-pyrach-a- sho 2.00 pn o tu Y ipmetyp)vminoimidavoi. Ba (3). sh and i t, 2-Vipyridazine-Z» 315-329 dk ilibenzamide (44), 383 i (2H), 507 i 00 iv ato? (Z) ta1- ! 7a (28, 7278 it (c), tvo

GI 85.10- ovivIn)

Iprikl. Structure Name Anaphytical data are not M-ethyl-hmethyl-a-ib42 | VT oo 0129 hem methyphenoxy)-B- | MUU dreams B; E about kov | about | Ktetrapdoo-eM-pnroanoYaya- | revealed - netyn, r ipmetiptaminogmidazoiy, | 8008 MU and: we . о ей Ху т.2-vBinridazine-Z- calculated that ilibenzamide Y "aa ! another 6 g s t | M-etyp-4-45-4-VH - 1.22 o i i I methoxyphenoxy)-B» MU oah : gav : o r. 5 i i Ktetrapdoo-eH-pyran-I- | revealed - ve genes WE And Dyak y; zhk ipmetyp)iaminoimidazoi!, | 516565 MUU

OZ S ev, ko, sk cya i that 2-Vipyridazine-ZyaYa)-2- calculated lu! x - ben g methylbenzamide - 515.6 u ne shshkhya

I

Beat | and t | Meethyl-a- in (2 second- KG is that one

We are methoxyphenoxy m В- МУ раци че, . . . and - kov I I I | Tstetrahydro-eNipiran-Yaya- and supposedly -

OK d- (pmetitaminsimidazoii, 5346 MU

M ey and S Zh. her, Shchnya!

Glue i- Sn, | 2-shtridasinoYa t is calculated

Her - to . about St. no 9 I I -5Z3B yet

SHESKITSAKH A AYESH 4 221

T | M-ethyla in (5-fluoro-a- VT zho 13 them methylphenoxy|-B- | Mu also in, Ktetrahydro-2H-pyran-4- | Nekhy zhk | ilmethypiaminesimidazoi, 5186 MU ! A, y- sov 2 -ipridazine-ya-pi-ya- / calculated what? metypbenzamide | - B17.6 - US

CT 1.25

Mu! | 5345 MUU were detected and -5336 were calculated by NMR (400 mg doM5O-en ab) Tertiary | 407 vnu and I Methyl-yachOch (Z rtor-a- 115429

MA methoxyphenoxy)-8- | I av I. ry (2; 1.82 80000000 tetrahedron tlteany zero

And i-d ivmethyl)aminethimidazoi,

Seya odipyridazine Z. en) SAME also - K. Bipyridazin-Z-ilU (zn) zv. about sv, C 2 methylbenzamide | zv NO o | 3.78-3.83 (NU, zva (Z); BOB

IN at 709 Nu 718-725 (28) 00780 (IN), 7 Vr. 789 (2H),

Precept, Structure | Name Dnapitic data

That pp and bat tav On, ! vyBiyN)

Assn. :

Щ riot M-ethyl-2-methyp-4-(6-02- tone 136 and g methylphenoxy)-B- MU in! Ar von Ka. 3,8- | it was revealed that S ve trifterpropipzaminoyiimi | 4955 MM. as dazogi 2-VipridazinoZ- | Ibenzamide was also calculated -497.5! mon iii pisk

MU was detected - calculated according to MM - 5315!

THERE (300

OK Mgz oM5O- not that M-ethyl 8-2 -fluoro-a- that " 5 methoxyphenoxt)-8- | ov iy

E ur 44. iov on) bo wa B silo propyl)aminoinmilyu sn), penya torprop/te: Yaiv " nitrogen 2 iridazle. | 7-9 Сn) ! Г | 3.734324

E s ipr-e-methypbenzamide | (Well, how are you? (Z), 6/6 mon B/V (NN), 76 ranu you? (Well, 7 a

PN), 7558.

Structure Name Anaphytical data

And 7.65 Well; 788 PN), 7.7. NU t, (IN); vy5IyN) -SHV, om! and sh! not phen M-ethyl-a-8-i5-fluoro-e- VT - 1.37

And g methyphenoxy)B- MALE

Tv a t ((3.8,3- revealed - sly Nm m SY s !

And - What is trifluoropropyl)iamino|mi | 516.5 mm; And dazog1,2-bipyridazinoZ- calculated it-e-methybenzamide - BIB vt e 132

MUM was found to be 532, MM: -5315 was calculated

OM, I k I o. etc. I T1H-YayaMe (500 mg of M-ethyl-a-(6-(3-rtorane | mg oM8O-

With methoxyphenoxy)-B- ot 96), "Trotie

B 59; KE / KO.5, i. и у: 604 as well as Czech Republic 507 (ZN), no, no, trifluoropropylaminoiy mi

Sun and r M | 213 (3H).

E "MH of azoi1,2-vipyridazin-i- which is produced with 2vi-ota

Co itr-e-methylbenzamide

And in (Nu 3.29 (2), 3.58 (YAN), Z yaA an 6.09 in, then 799 (IN), 717-720

Application Structure Name (Avagitized data! (IN, TYA

IN

73 in), 7,63-768 (ni ot7v pn, thes

inv)

the grove

And we are your lake

500.5 MAL of MUU was found and calculated

And "99.5

YIN-NMR. (300

I mMgya OM8Ove av), is frpie iy I aivaotov (Well

Zh M difluoroethylaminoi-6-(2-2 vn, biy Frishi zl (Nu

BOB -x What What 377 sn, t Z ky sn, methoxyphenoxy midazo z vv pn) t ho G2-B)pyridazin- 3-1 M sv, nn, ethyl-?-methybenzamide Bk Nx ne ba pn 7.06 (1),

OH 00; tva anu 7.58-7.65

NU 0789. (for sleep, tav an,

VI IN)

Pryka |Structure Name Analytical: data

EC

1 I - that ach VT ho 1228

Tv difluoroethylamino-Я45- 1 MM in 7 vu Ffluor-- detected - skin | I am: WE ARE methyphenoxy)midazor! | 484.5 MU

SY and 2 Vipyridazin-Z-il- it was calculated that ethyp-2-methypbenzamide - 483.5 o sn, v.

CT ho 1.54 tMn 48-43 ! !

KB dyk, Zh m ozh MM? not and av difluorophenoxy)-8-n2- ek, oh UVI and | | 507 and 42 MU of methoxyethylamine imide were detected

For 11,2-bipyridazine-3-yl, 1, M-ethyl-2-methylbenzamide was calculated as 481.5 and

Sh sn, | pi t v. ; M 448-2-fluoro-ia ugoya sn, "Yan -ethyl-446(2-fluoro-ia" and ra Y piichk, du M . MUu

Ka Y t tu methoxyphenoxy) i» p. to, Although revealed -

VO. n methoxyethylaminopyrimida shi and r. | "45 MM; and eov. zo 1.2: Vipyridazin-v-il 7 V | calculated ev 2-methylovnzamide nm x 483.5 y and ze ay yak, VT - 127 yu t MD !

E i zn M-ethyl-a in 5-fluoro was found - with M, methicphenoxy)-in-n- 478.5 MmuUu

Uch ІІ in | y and by m of methoxyethylaminoimide with calculated /

With Сn : and I zo11,2-vipyridazin-Y-yl)» | 4775 re 2-methylbenzamide 1NAYAMe (300 not in E: Mgz oM5o- 48). I am Irotov

The following Intermediates were prepared analogously to the procedure described above in Example 562a using the appropriate amine and the appropriate boronic acid LC-MS data such as retention time (CT in min) or mass peak observed were collected using LC-MS

Method A, unless otherwise noted):

Prom.

Strysura Name Analytical data

Pryka

I would like a CT scan

MU discovered them

AtAd MUM calculated and -a73A! 1n-jaMe. (300

MG, om8o- 7 Ya Oz roti: ko Y 237 (N

C 4(6-bromo-84(2-Y and chn 242 (4H), as their "morpholine-Y- - also in 6 Pe АХ shk and ; y Э 2 2.5a (2H), and ooek UM ilretigtamnoimdavo ge vyti 3 mo 273 (ZN), rakh "pYaiirkdazin-Z-il)-Me-

Cohen, itvid ) 328 (on), yo chash dimetibenzamid I !

Which is 349-359 years old (4). 842

SNU; 74 (2). 7,565- ! 7.53 i, i.e. IN, 792 IN, 796 (IN),

VN) tu r 109 and y ! still MU

H ach 5'bromo-8 tetrahydro- | discovered oh

J

! in o 2H-pyran-y- zschoa MM

Oh what and I zata Ma ipmethyl)iaminoimidazo!!, And calculated. t 2-Vipyridazine-3Y-M2- | khaBVA shi sv - . ! ,

K dimethypienzamid TNUYAMe (300 ik; not Mgz oM5Os-sn; ab, - Trrtiye

Structure Name Analytical data

Application !

I, III, and I, sometimes (NU VZ 188 IN),

Z (ZN), 2.89-2.78 (ZNU zi ! 3.27 (NN), for (23, 842 (NI, and 00 mon 7.86 (NN), 785800 (ZNU, 818 an shk shi shi

ATO VO

MU was detected (- 457.3 MM calculated g. 2 455.3 cha | 446-Bromo-B4 ((3, 3.3" nym (400. which, trifluoropropyl)aminoimi | MHz "MBO. z/4a wk dazog and 2-Vytridazine-ya- 96) - pp: it ilum o: 237 (well not and dimethyloenzamide 2.59-9.71 an (2nu 273 (Z), 3.59 (2), bab (Nu and iy tab

SN, 7.85.

And prom, ! | .

Structure Name Analytical data

Pryka tva (Nu 7,87 (IN), vl17 In)

Her x 1703

MU

: found - 425.3 MUCH calculated layers

TNeNMR: (400

Bi E MGTS MO» tk | av), "Irrtiv

And 446 bromo-B(2,2- Shchi ee, and vmineo 28 (3

SooAvozhiY difluoroethyliauminoi Mida and vva vin 273 (ZV). j Zo 2-Vipyridazin-z-igu" I i 325 (B). in M. 2-dimethylovnzamide Shk in z85B 2), their Ty, ! sleep 62, tA av, ti ON), 7.52 (IN), 7.57-8.03 en vii av)

Structure Name Analytical data

Pryka

CT I oo

MM detected - 4593 MU calculated - 418.3 yin-yaMe. (300 sm, MHz oMBO-

Sho 46), "rr re and 4-16-bromo-8-(o- 237 (an),

In Kf of methoxystylaminoimide | 2:73 (3),

Y Ex z011,2-ypyridazin-z-yl. | 3.25 (Z),

We em, M,2-dimethylbenzamide 353 (YAN), oto 8; (nu t tA YN t In) 7.86 Sn, 7.89-7.94

МН 0785 inu 0 vyv

Mon shi | | NT open with | MU about I was found 2 m 44(6-bromo-8-(2" zva MU b eeM, (morpholine-4- calculated

Ba visi ilietiliamnnommidazoi1,2 | from 4878

SU 2n, -vipividazineZ-Yip)- M» 1nAyaYAMe 1400 io etyp-?-mMethyloenzamide Mgts MBO. and | av), - (it turns out that 108-112 sho (Z). 237

Prom, Sh NI | T | What

Structure Name Analytical data (ZNU 242. (4H), 2.58 (NU ZY v- 388) 3.43 SN), 352-358 (YAN), bain iz (ShN 787 in OB (1), 7.81 n), 7.55 in va? sn) in | BT oh m?

MUM was found Ш 4734 М calculated and Ш E «4724

P. 448-bromo-8-Ktetrahydro-TYAM in chn MG; OoM8O- sykoem, 2H-piran-a- Y and 5VIZ that I ipmetitamino| midazoi, 25 owls" I

In sim 2-Ipyridazin-Z-ip ich" rai 72 su (ZNU 0 ev ethyl--e-methybenzamide | and

RI No (2. - | 158 on) 1895 1, 2.37 eta

From 18-3.25 (VNU 38 (2nH) 842

IN

Structure Name Analytical data

Attribute

NU 07av and o0lv5

PU 0788 ! 7.98 (ZN), 8.22 (B)

BT zho 125

MU

! discovered at: yati MA calculated - 4703 1Н-ЯМе (400 ! and MHz оМ5О-

J

Ot 98) i (but what 4-(6-bromo-84(3,3,3-

Y f slaminoim 1.08 (ZNO, all trifluoropropylaminoimy Y

Doi aty 237 (VN) bota Vb dazo/1,2-ripyridazine-Z- ! . Saint 2.56 (Well,

Mk ipuMethyloo- SHY

Mo | | 818-326 and I methylenzamide! 7 "nn (2); 359

Also (SNU 846 ay. (x 7.85 well 0 tv 7.56 (en 758, wine)

Prom:

Structure of Chazva Analytical data

Application : 1 CT - 10

We found out that 4393 MUU were calculated

And - DZZ

IN-NMR. (300 pi mg oM8O- "kn i i | 96) i Trrti: strain, 4-8-bromo-8-(2,2- shock. | I T69 iZNu wine difluoroethylaminoimid both | a zo 2-odi shchi and gZNI,

SiЬ ЧА: I Zog1.2-o|pyridazin-z-ylide sm, PO zivaov he | Metyp-2-mMetypbenzamide |... that (ZNM Zv che snu vet, y. to) yNM o 786 (U 07vo- 7.55 PN) 1799 (2Н) 823 1) tu 109 ! He still | discovered - sn | 4338 0 M

А M 1 4х5-bromo-8-e-calculated methoxyethyptuaminosimide compound | - 4323 company Vot i: ; : ! and I zog1,2-01pyridazinez-it" | 1H-NMR (300 a Z; M-ethyl-2-methylbenzamide MHz OMVO", not 98). with (roti: and ! not 1.09 (Z), but (ZN), 318-327

Prom; and

Structure Name Analytical data

acc. an), zas

And K

3.58 YBN). 543 CHI tva (nu tvo Inu 7.88 cha 783 in) tav v), ! scha IN) !

Intermediate Example 5826

I4-(ethylcarbamoyl)-3-methylphenyl|boronic acid (c) o; m" Y

N MTU Fr. --I N ; c c) It contains 17.72 g (61.27 mmol) of M-ethyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-daoxaborolan-2-yl)benzamide, which was obtained according to Intermediate Example 582c, was converted similarly

Intermediate Example 5626 with the receipt after processing and purification of 8.75 g (70 95) of the title compound.

Intermediate Example 582 p

M-ethyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-daoxaborolan-2-yl)benzamide (c) (c) se el

High school - - - Ov

To a stirred solution of 15 g (57 mmol) of 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-daoxaborolan-2-yl)/ubenzoic acid in MMP (20 ml) was added 85, 84 ml (171.68 mmol) of ethylamine and 72.8 ml of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (114.45 mmol, 2M in TNE), and the mixture was stirred for 2 hours at room temperature to obtain after treatment and purification 16.00 g (96.7 95) of the title compound.

Pharmaceutical compositions of compounds of the invention

The present invention also relates to pharmaceutical compositions containing one or more compounds of the present invention. These compositions can be used to achieve the desired effect when administered to a patient in need thereof. A patient, for the purposes of this invention, is a mammal, including a human, in need of treatment for a particular condition or disease. Therefore, the present invention includes pharmaceutical compositions consisting of a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound or a salt thereof of the present invention. A pharmaceutically acceptable carrier is preferably a carrier that is relatively non-toxic and harmless to the patient, at a concentration that provides effective activity of the active ingredient, so that any side effects attributed to the carrier do not impair the beneficial effects of the active ingredient.

A pharmaceutically effective amount of a compound is preferably an amount that provides an effect or effect on a particular condition being treated. The compounds of the present invention may be administered with pharmaceutically acceptable carriers well known in the art using any conventional effective dosage form, including immediate, sustained and timed release dosage forms, oral, parenteral, topical, nasal, ophthalmic, optical, sublingual, rectal. , vaginal, etc.

For oral administration, the compounds may be formulated into solid or liquid dosage forms, such as capsules, pills, tablets, lozenges, lozenges, melts, powders, solutions, suspensions or emulsions, and may be prepared by methods known in the art for the manufacture of pharmaceutical compositions. . Solid dosage forms can be presented as a capsule of the usual hard- or soft-gelatin type, which contains, for example, surfactants, lubricants, and inert fillers such as lactose, sucrose, calcium phosphate, and corn starch.

In another embodiment, the compounds of the present invention may be tableted with conventional tablet excipients such as lactose, sucrose and corn starch in combination with binders such as acacia, corn starch or gelatin, disintegrating agents to aid disintegration and dissolution tablets after injection, such as potato starch, alginic acid, corn starch, and guar gum, gum tragacanth, acacia; lubricants that improve the granulation flow of the tablet and prevent adhesion of the tablet material to the surface of the tablet and punch colorants, such as talc, stearic acid, or magnesium, calcium, or zinc stearate, dyes, colors, and flavorings, such as peppermint, oil of wintergreen, or cherry aroma, to improve the aesthetic properties of tablets and make them more acceptable to the patient.

Acceptable excipients for use in oral liquid dosage forms include calcium diphosphate, and solvents such as water and alcohols, such as ethanol, benzyl alcohol, and polyethylene alcohols, with or without the addition of a pharmaceutically acceptable surfactant, suspending agent, or emulsifier. Other various materials may be present as a coating or otherwise modify the physical form of the dosage unit.

Tablets, pills, or capsules may be coated with shellac, sugar, or both.

Dispersible powders and granules are suitable for obtaining an aqueous suspension. They provide the active ingredient in admixture with a dispersing or wetting agent, a suspending agent, and one or more preservatives. Suitable dispersing or wetting agents are listed above. Additional excipients may also be present, such as the sweeteners, flavors and colors described above.

Pharmaceutical compositions of the present invention can also be in the form of an oil-in-water emulsion.

The oil phase can be represented by a vegetable oil such as liquid paraffin or a mixture of vegetable oils. Suitable emulsifiers include (1) natural resins such as acacia resin and tragacanth resin, (2) natural phosphatides such as soy and lecithin, (3) esters or partial esters derived from fatty acid anhydrides and hexitol, such as sorbitan monooleate , (4) condensation products of the indicated partial esters with ethylene oxide, for example, polyoxyethylene sorbitan monooleate. Emulsions may also contain sweeteners and flavorings.

Oil suspensions can be formulated by suspending the active ingredient in a vegetable oil such as, for example, peanut oil, olive oil, sesame oil or coconut oil or in a mineral oil such as liquid paraffin. Oil suspensions may contain a thickener such as, for example, beeswax, solid paraffin or cetyl alcohol. Suspensions may also contain one or more preservatives, for example, ethyl or n-propyl p-hydroxybenzoate; one or more dyes; one or more flavorings; and one or more sweeteners such as sucrose or saccharin.

Syrups and elixirs are formulated with sweeteners such as, for example, glycerin, propylene glycol, sorbitol, or sucrose. Such compositions may also contain an emollient and preservative, such as methyl and propyl parabens, and fragrances and dyes.

The compounds of the present invention may also be administered parenterally, i.e., subcutaneously, intravenously, intraocularly, intrasynovially, intramuscularly, or interperitoneally, as injectable doses of the compound in a preferably physiologically acceptable solvent with a pharmaceutical carrier, which may be represented by cetril liquid or a mixture of liquids, such as water, saline, aqueous dextrose and bound sugar solutions, alcohol such as ethanol, isopropanol or hexadecyl alcohol, glycols such as propylene glycol or polyethylene glycol, glycerol ketals such as 2,2-dimethyl-1,1 -dioxolane-4-methanol, ethers such as poly(ethylene glycol) 400, oil, fatty acid, fatty acid ester or, fatty acid glyceride or acetylated fatty acid glyceride, with or without the addition of a pharmaceutically acceptable surfactant such as soap or a detergent, suspending agent such as pectin,

carbomer, methylcellulose, hydroxypropylmethylcellulose or carboxymethylcellulose or emulsifier and other pharmaceutical excipients.

Examples of oils that can be used in the parenteral dosage forms of the present invention include petroleum, oils of animal, vegetable or artificial origin, for example, peanut oil, soybean oil, sesame oil, cottonseed oil, corn oil, olive oil, petrolatum and mineral oil. Suitable fatty acids include oleic acid, stearic acid, isostearic acid and myristic acid. Suitable fatty acid esters include, for example, ethyl oleate and isopropyl myristate. Suitable soaps include alkali metal and fatty acid salts, ammonium and triethanolamine, and suitable detergents include cationic detergents, for example, dimethyl dialkyl ammonium halides, -alkyl pyridine halides, and alkylamine acetates; anionic detergents, for example, alkyl, aryl, and olefin sulfonates, alkyl, olefin, ether, and monoglyceride sulfates, and sulfosuccinates; non-ionic detergents, for example, oxides of fatty amines, alkanolamides of fatty acids, and copolymers of poly(oxyethylene-oxypropylene)s or ethylene oxide or propylene oxide; and amphoteric detergents, such as alkyl beta-aminopropionates, and 2-alkylimidazoline quaternary ammonium salts, and mixtures.

Parenteral compositions of the present invention usually contain from about 0.595 to about 25 wt. 95 active ingredients in solution. Preservatives and buffers can also preferably be used. To minimize or avoid irritation at the injection site, such compositions may contain non-ionic surfactants with a hydrophilic-lipophilic balance (HIB) preferably from about 12 to about 17. The amount of surfactant in such compositions preferably ranges from about 5 95 to about 15 wt. 95. Surfactant can be a separate component with the above

A NIV or can be a mixture of two or more components with a desired NIV.

Examples of surfactants used in parenteral formulations include a class of polyethylene sorbitan fatty acid esters, such as sorbitan monooleate and high molecular weight adducts of ethylene oxide with a hydrophobic base formed by condensation of propylene oxide with propylene glycol.

Pharmaceutical compositions can be in the form of a sterile injectable aqueous suspension. Such suspensions can be formulated by methods using dispersing or wetting agents and suspending agents such as, for example, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth, and gum acacia; dispersing or wetting agents, which may be phosphatides of natural origin, such as lecithin, a condensation product of an alkylene oxide with a fatty acid, for example, polyoxyethylene stearate, a condensation product of ethylene oxide with a long-chain aliphatic alcohol, for example, heptadecaethyl oxyethanol, a condensation product of ethylene oxide with a partial ester of a fatty acid and hexitol, such as polyoxyethylene sorbitol monooleate, or a condensation product of ethylene oxide with a partial ester of a fatty acid and hexitol anhydride, for example, polyoxyethylene sorbitan monooleate.

The sterile injectable form may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent.

Diluents and solvents used include, for example, water, Ringer's solution, isotonic sodium chloride solutions, and isotonic glucose solutions. In addition, sterile bound oils are commonly used as solvents or suspending media. For this purpose, any mixture, bound oil, including synthetic mono- or diglycerides, is used.

In addition, fatty acids such as oleic acid are used to make injectable forms.

The composition of the invention can also be administered in the form of suppositories for rectal administration of the medicinal product. These compositions are prepared by mixing the drug with a suitable non-irritating excipient which is solid at room temperature but liquid at rectal temperature and will therefore melt in the rectum to release the drug. Such materials include, for example, cocoa butter and polyethylene glycol.

Other compositions used in the methods of this invention include transdermal delivery devices ("patches"). Such transdermal patches are used to provide continuous or intermittent infusion of the compound of this invention in a controlled amount. The structure and use of transdermal patches for the delivery of pharmaceutical agents are well known in the art (see, for example, US Pat. No. 5,023,252, issued June 11, 1991, incorporated herein by reference).

Such patches can be designed for continuous, pulsatile, or on-demand delivery of pharmaceutical agents.

Controlled release compositions for parenteral administration include liposome compositions, polymeric microspheres, and polymeric gel compositions known in the art.

It may be desirable or necessary to administer the pharmaceutical composition to the patient using a mechanical delivery device. Designs and applications of mechanical means for delivering pharmaceutical agents are well known in the art. Direct techniques for, for example, the introduction of a drug directly into the brain usually involve the installation of a catheter to deliver the drug into the patient's ventricular system to pass the blood-brain barrier. One such implantable delivery system used to transport agents to specific anatomical regions of the body is described in US Patent 5,011,472, issued April 30, 1991.

The compositions of the invention may also contain other conventional pharmaceutically acceptable admixture ingredients, usually carriers or diluents, as needed or desired.

Conventional procedures can be used to prepare such compositions in appropriate dosage forms. Such ingredients and procedures include those described in the following references, each of which is incorporated herein by reference: Romei, M.RE. ei ai., "Sotrepaisht oi Ekhsiriepiv 7tog Ragepivga! Eoptiiaiopv" ROA doshgpai oi Rnaptaseshisa! bsiepse 8

Tesppoiosdu 1998, 52(5), 238-311; ZpisKIieu, V.S "Ragepiegta! Eoptyiayope oi Ztai! Moiiiesshe TPnegareshisv MagkkKeiyevd ip She Opiiied 5iagez (1999)-Rap-1" ROA uoshtai oi Rnaptaseshisa! Zsiepse 8

Thesppoiodu 1999, 53(6), 324-349; apa Meta, 5. eyi ai., "Ekhsiriepiz apa TNneig Ove ip Ipiesiarie

Rhodysiv" ROA doshgpai oi Rnaptaseciysa! Zsiepse 5 Thesppoiodu 1997, 51(4), 166-171.

Commonly used pharmaceutical ingredients used to create compositions for a particular route of administration include: acidifying agents (examples include, but are not limited to: acetic acid, citric acid, fumarolic acid, hydrochloric acid, nitric acid); alkalizing agents (examples include, but are not limited to, ammonia solution, ammonium carbonate, diethanolamine, monoethanolamine, potassium hydroxide, sodium borate, sodium carbonate, sodium hydroxide, triethanolamine, trolamine); adsorbents (examples include, but are not limited to, powdered cellulose and activated carbon); aerosol propellants (examples include, but are not limited to, carbon dioxide, ССИ2Е2, B2СИС-ССИЕ2, and ССИЕЗ) air displacing agents (examples include, but are not limited to: nitrogen and argon); antifungal preservatives (examples include, but are not limited to, benzoic acid, butylparaben, ethylparaben, methylparaben, propylparaben, sodium benzoate); antimicrobial preservatives (examples include, but are not limited to, benzalkonium chloride, benzethonium chloride, benzyl alcohol, cetylpyridinium chloride, chlorobutanol, phenol, phenylethyl alcohol, phenylmercuric nitrate, and thimerosal); antioxidants (examples include, but are not limited to, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, phosphorous acid, monothioglycerin, propyl gallate, sodium ascorbate, sodium bisulfite, sodium formaldehyde sulfoxylate, sodium metabisulfite); binders (examples include, but are not limited to, block polymers, natural and synthetic rubber, polyacrylates, polyurethanes, silicon compounds, polysiloxanes, and butadiene-styrene copolymers); buffering agents (examples include, but are not limited to: potassium metaphosphate, dipotassium phosphate, sodium acetate, anhydrous sodium citrate, and sodium citrate dihydrate) carriers (examples include, but are not limited to: acacia syrup, aromatic syrup, aromatic elixir, cherry syrup, cocoa syrup, orange syrup, syrup, corn oil, mineral oil, peanut oil, sesame oil, bacteriostatic sodium chloride injection and bacteriostatic water for injection) chelating agents (examples include, but are not limited to: edetate disodium and edetic acid ) dyes (examples include, but are not limited to the following: EOZS Kea Mo. 3, ErasS

Wea Mo. 20, EOaS MePom Mo. 6, ras Vieux Mo. 2, 080 Steep Mo. 5, 08 Ogapde Mo. 5, 080 Way

Mo. 8, caramel and iron oxide red); (610) clarifiers (examples include, but are not limited to: bentonite);

emulsifiers (examples include, but are not limited to, acacia, cetomacrogol, cetyl alcohol, glyceryl monostearate, lecithin, sorbitan monooleate, polyoxyethylene 50 monostearate); sealants (examples include, but are not limited to: gelatin and cellulose acetate phthalate) flavors (examples include, but are not limited to: anise oil, cinnamon oil, cocoa, menthol, orange oil, peppermint oil, and vanillin); humectants (examples include, but are not limited to, glycerin, propylene glycol, and sorbitol); grinding agents (examples include, but are not limited to, mineral oil and glycerin); oils (examples include, but are not limited to, peanut butter, mineral oil, olive oil, peanut oil, sesame oil, and vegetable oil); ointment bases (examples include, but are not limited to, lanolin, hydrophilic ointments, polyethylene glycol ointment, petrolatum, hydrophilic petrolatum, white ointment, yellow ointment, and rosewater-based ointment); penetration enhancers (transdermal delivery) (examples include but are not limited to the following: monohydroxy or polyhydroxy alcohols, mono- or polyhydric alcohols, saturated or unsaturated fatty alcohols, saturated or unsaturated fatty esters, saturated or unsaturated dicarboxylic acids, essential oils, phosphatidyl derivatives, cephalin, terpenes, amides, ethers, ketones, and ureas) plasticizers (examples include, but are not limited to, diethyl phthalate and glycerin); solvents (examples include, but are not limited to, ethanol, corn oil, cottonseed oil, glycerin, isopropanol, mineral oil, oleic acid, peanut oil, purified water, water for injection, sterile water for injection, and sterile water for washing); thickeners (examples include, but are not limited to, cetyl alcohol, cetyl wax esters, microcrystalline wax, paraffin, stearyl alcohol, white wax, and yellow wax); suppository bases (examples include, but are not limited to: cocoa butter and polyethylene glycols (mixtures); surfactants (examples include, but are not limited to: benzalkonium chloride, nonoxynol 10, oxtoxinol 9, polysorbate 80, sodium lauryl sulfate, and sorbitan mono -palmitate); suspending agents (examples include, but not limited to: agar, bentonite, carbomer, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, kaolin, methylcellulose, tragacanth, and wigum); sweeteners (examples include, but not limited to: aspartame , dextrose, glycerin, mannitol, propylene glycol, sodium saccharin, sorbitol, and sucrose); tablet anti-caking agents (examples include, but are not limited to: magnesium stearate and talc); tablet binding agents (examples include, but are not limited to: acacia, alginic acid, sodium carboxymethylcellulose, compressed sugar p, ethyl cellulose, gelatin, liquid glucose, methyl cellulose, non-cross-linked polyvinylpyrrolidone and pregelatinized starch); tablet and capsule diluents (examples include, but are not limited to, dibasic calcium phosphate, kaolin, lactose, mannitol, microcrystalline cellulose, powdered cellulose, precipitated calcium carbonate, sodium carbonate, sodium phosphate, sorbitol, and starch); tablet coating agents (examples include, but are not limited to, liquid glucose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetate phthalate, and shellac); direct compression tablet excipients (examples include, but are not limited to: dibasic calcium phosphate); tablet disintegrants (examples include, but are not limited to, alginic acid, calcium carboxymethyl cellulose, microcrystalline cellulose, polacrilin potassium, cross-linked polyvinylpyrrolidone, sodium alginate, sodium starch glycolate, and starch);

hawthorn anti pills (examples include, but are not limited to, colloidal silica, cornstarch, and talc); tablet lubricants (examples include, but are not limited to, calcium stearate, magnesium stearate, mineral oil, stearic acid, and zinc stearate); tablet/capsule opacifying agents (examples include, but are not limited to: titanium dioxide); tablet polishing agents (examples include, but are not limited to, carnauba wax and white wax); thickeners (examples include, but are not limited to, beeswax, cetyl alcohol, and paraffin); tonicity agents (examples include, but are not limited to, dextrose and sodium chloride); viscosity-increasing agents (examples include, but are not limited to, alginic acid, bentonite, carbomers, sodium carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone, sodium alginate, and tragacanth); and humectants (examples include, but are not limited to, heptadecaethylene oxyethanol, lecithins, sorbitol monooleate, polyoxyethylene sorbitol monooleate, and polyoxyethylene stearate).

The pharmaceutical compositions of this invention are described as follows:

Sterile IM Solution: A 5 mg/ml solution of the desired compound of the present invention is prepared using sterile water for injection, and the pH is adjusted as necessary. The solution was diluted for administration to 1-2 mg/ml with sterile 5 95 dextrose and administered as an IM infusion over approximately 60 min.

Lyophilized powder for IM administration: a sterile composition is obtained from (i) 100 - 1000 mg of the desired compound of the present invention as a lyophilized powder, (ii) 32 - 327 mg/ml sodium citrate, and (ii) 300 - 3000 mg of Dextran 40. The composition was reconstituted with sterile saline for injection or 5 95 dextrose to a concentration of 10-20 mg/ml, which was then diluted with saline or 5 95 dextrose to 0.2 - 0.4 mg/ml, and administered either IM tablet or IM infusion for 15 - 60 min.

Intramuscular suspension: the following solution or suspension was prepared for intramuscular injection: 50 mg/ml of the desired water-insoluble compound of the invention 5 mg/ml sodium carboxymethylcellulose 4 mg/ml TM/EEM 80 9 mg/ml sodium chloride 9 mg /ml of benzyl alcohol

Hard Shell Capsules: A significant number of capsules were obtained by filling a standard two-part galantine capsule, where each capsule contained 100 mg of powdered active ingredient, 150 mg of lactose, 50 mg of cellulose, and 6 mg of magnesium stearate.

Soft Gelatin Capsules: A mixture of the active ingredient in a digestible oil, such as soybean oil, cottonseed oil, or olive oil, was prepared and injected using a piston pump into molten gelatin to form a soft gelatin capsule containing 100 mg of the active ingredient. . The capsules were washed and dried. The active ingredient was dissolved in a mixture of polyethylene glycol, glycerin and sorbitol to obtain a water-miscible medical mixture.

Tablets: A substantial number of tablets were prepared by conventional methods such that a dosage unit contained 100 mg of active ingredient, 0.2 mg of colloidal silicon dioxide, 5 mg of magnesium stearate, 275 mg of microcrystalline cellulose, 11 mg of starch, and 98.8 mg of lactose.

Appropriate aqueous and non-aqueous coatings were applied to improve palatability, appearance and stability or delay absorption.

Immediate-release tablets/capsules: Presented in solid oral dosage forms prepared by standard and novel methods. These forms are taken orally without water for instant dissolution and delivery of the drug. The active ingredient is mixed in a liquid that contains ingredients such as sugar, gelatin, pectin and sweeteners. These liquids are solidified into solid tablets or capsules by freeze-drying and solid state extraction. Compounds of the drug are pressed with viscoelastic and thermoplastic resins and polymers of effervescent components to obtain porous matrices aimed at instant release without the need for water.

Combined treatment

The compounds of the present invention can be administered as a single pharmaceutical agent or in combination with one or more other pharmaceutical agents where the combination does not cause unacceptable side effects. The present invention also relates to such combinations. For example, the compounds of the present invention can be combined with known anti-gaper-proliferative or other agents, etc., as well as with impurities and their combinations. Other agents include, but are not limited to, anti-angiogenic agents, mitosis inhibitors, alkylating agents, anti-metabolites, DNA-intercalating antibiotics, growth factor inhibitors, cell cycle inhibitors, enzyme inhibitors, topoisomerase inhibitors, biological response modifiers, or anti- hormones

An additional pharmaceutical agent can be affinitor, aldesleukin, alendronic acid, alphaferon, alitretinoin, allopurinol, aloprim, aloxy, altretamine, aminoglutethimide, amifostine, ambrubicin, amsacrine, anastrozole, anzmet, aranesp, arglabin, arsenic trioxide, aromasin, 5-azacytidine , azathioprine, BSO or Thais BSO, bestatin, betamethasone acetate, betamethasone sodium phosphate, bexarotene, bleomycin sulfate, broxuridine, bortezomib, busulfan, calcitonin, campat, capecitabine, carboplatin, cazodex, cefezone, celmoleukin, cerubidin, chlorambucil, cisplatin, cladribine, clodronic acid, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunox, decadron, decadron phosphate, delestrogen, denileukin diphtitox, depo-medrol, deslorelin, dexrazoxane, diethylstilbestrol, diflucan, docetaxel, doxyfluridine, doxorubicin, dronabinol, YMU-166NS, eligard, elitek , elens, emend, epirubicin, epoetin alfa, epogen, heptaplatin, ergamizol, estras, estradiol, estramustine sodium phosphate, ethinyl estradiol, etiol, etidronic acid, etopofos, etoposide, fadrozole, farstone, filgrastim, finasteride, fligrastim, floxuridine, fluconazole, fludarabine, 5-fluorodeoxyuridine monophosphate, 5-fluorouracil (5-3), fluoxymesterone, flutamide, formestane, fosteabine, fotemustine, fulvestrant , gammagard, gemcitabine, gemtuzumab, Gleevec, gliadel, goserelin, granisetron NS, histrelin, hycamtin, hydrocorton, erythro-hydroxynoniladenine, hydroxyurea, ibritumomab tiuxetan, idarubicin, ifosfamide, interferon alpha, interferon-alpha 2, interferon alfa-2A, interferon alfa -2B, interferon alfa-p!, interferon alfa-p3, interferon beta, interferon gamma-ia, interleukin-2, intron A, Iresa, irinotecan, kytril, lapatinib, lentinan sulfate, letrozole, leucovorin, leuprolide, leuprolide acetate, levamisole , levofolinic acid calcium salt, levothroid, levoxyl, lomustine, lonidamine, marinol, mechlorethamine, mecobalamin, medroxyprogesterone acetate, megestrol acetate, melphalan, menest, b6-mercaptopurine, Mesna, methotrexate, metvix, mi Ltefosine, minocycline, mitomycin C, mitotane, mitoxantrone, Modrenal,

Myocet, nedaplatin, neulasta, neumega, neupogen, nilutamide, nolvadex, MZS-631570, OST-43, octreotide, ondansetron NSI, orapred, oxaliplatin, paclitaxel, pediapred, pegaspargas,

Pegasis, pentostatin, pizibanil, pilocarpine NOSI, pirrubicin, plicamycin, porfimer sodium, prednimustine, prednisone, prednisone, premarin, procarbazine, procrit, raltitrexed, KOEA 119, rebif, rhenium-186 etidronate, rituximab, roferon-A, romurtide, salagen, sandostatin, sargramostim, semustine, sisofiran, sobuzoxan, solu-medrol, sparfosofic acid, stem cell therapy, streptozocin, strontium-89 chloride, sunitinib, synthroid, tamoxifen, tamsulosin, tazonermin, tastolactone, taxotere, tezeleukin, temozolomide, teniposide, testosterone propionate , testred, thioguanine, thiotepa, thyrotropin, tiludronic acid, topotecan, toremifene, tozitumomab, trastuzumab, treosulfan, tretinoin, trexal, trimethylmelamine, trimetrexate, triptorelin acetate, triptorelin pamoate, OET, uridine, valrubicin, vesnarinone, vinblastine, vincristine, vindine, vinorelbine, virulisin, zinekard, zinostatin stimalamer, zofran, AVI-007, acolbifen, actimun, afinitac, aminopterin, arzoxifene, azoprisnil, atamestan, atrasentan, sorafenib (VAM 43-9006), avastin, SSI-779, SOS-501, celebrex, cetuximab, krisnatol, cyproterone acetate, lecitabine, OM-101, doxorubicin-MTS, azyI!m, dutasteride, edotecarin, eflornithine, exatecan, fenretinide , histamine dihydrochloride, histrelin hydrogel implant, holmium-166 UOTMR, ibandronic acid, interferon gamma, intron-RES, ixabepilone, cochlear lymph hemocyanin, I -651582, lanreotide, lasofoxifene, libra, lonafarnib, miproxifene, minodronate, M5-209, liposomal MTR-RE, MX-6, nafarelin, nemorubicin, neovastat, nolatrexed, oblimersen, onco-TS5, ozidem, paclitaxel polyglutamate, pamidronate disodium, RM-401, 05-21, quazepam, K-1549, raloxifene, narpirnas, 13- cis-retinoic acid, satraplatin, seocalcitol, T-138067, tarseva, taxoprexin, thymosin alpha 1, thiazofurin, tipifarnib, tirapazamine, TI K-286, toremifene, Tgap5MIO-107B, valspodar, vapreotide, vatalanib, verteporfin, vinflunine, 2- 100, zolendronic acid or their combinations.

Optional anti-hyperproliferative agents to be added to the composition include, (610) but are not limited to the following: compounds listed in Cancer Chemotherapy, 11th Ed.

Ipayeh, (1996), which is incorporated herein by reference, such as asparaginase, bleomycin, carboplatin, carmustine, chlorambucil, cisplatin, colaspas, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, doxorubicin (adriamycin), epirubicin, epothilone , epothilone derivative, etoposide, 5-fluorouracil, hexamethylmelamine, hydroxyurea, ifosfamide, irinotecan, leucovorin, lomustine, mechlorethamine, b-mercaptopurine, mesna, methotrexate, mitomycin C, mitoxantrone, prednisone, prednisone, procarbazine, raloxifene, streptozocin, tamoxifen, thioguanine , topotecan, vinblastine, vincristine and vindesine.

Other anti-hyperproliferative agents suitable for use with the composition of the invention include, but are not limited to the following: compounds used in the treatment of nonplastic diseases in boodtap apa Sitap' Te RPaptasoyodisa! Vazib5 oi Tnegareshisv (Mipii Eaiiop), edyog Moiipoi ei ai., fish. Bu MesStham/-NIII, rade5 1225-1287, (1996), which is incorporated herein by reference, such as aminoglutethimide, I -asparaginase, azathioprine, 5-azacytidine cladribine, busulfan, diethylstilbestrol, 2",2'- difluorodeoxycytidine, docetaxel, erythrohydroxynonyl adenine, ethinyl estradiol, 5-fluorodeoxyuridine,

B-fluorodeoxyuridine monophosphate, fludarabine phosphate, fluoxymesterone, flutamide, hydroxyprogesterone caproate, idarubicin, interferon, medroxyprogesterone acetate, megestrol acetate, melphalan, mitotane, paclitaxel, pentosatin, M-phosphonoacetyl-i! -aspartate (RAGA), plicamycin, semustine, teniposide, testosterone propionate, thiotepa, trimethylmelamine, uridine and vinorelbine.

Other anti-hyperproliferative agents suitable for use with the composition of the invention include, but are not limited to, other anti-cancer agents such as epothilone and its derivatives, irinotecan, raloxifene and topotecan.

The compounds of the invention can also be administered in combination with bileu drugs.

Such protein drugs suitable for the treatment of cancer or other angiogenic disorders and for use with the compositions of the invention include, but are not limited to, the following: interferon (e.g., interferon alpha, beta, or gamma) supra-agonistic monoclonal antibodies, Tuebingen, vaccinia with TKR-1 protein , Colostrinin, anti-PAP antibody, UN-16, gemtuzumab, infliximab, cetuximab, trastuzumab, denileukin diftitox, rituximab, thymosin alpha 1, bevacizumab, mecasermin, mecasermin rinfabate, oprelvekin, natalizumab, gpMVi,

MEEBE-SR14-20-2767-Р, AVT-828, EgtB2-specific immunotoxin, 50M-35, MT-103, rinfabat,

A5-1402, B43-genistein, radioimmunotherapeutic agents based on I/-19, AS-9301, MM-EBO-1 vaccine, IMS-1C11, ST-322, ptOS10, "("t)SAR, MOVAB-009, aviscumin , MOH-1307, Neg!-2 vaccine,

ARS-8024, MOaV-NTME, t/pNI,3, I2M-311, Endostatin, volociximab, RKO-1762, lexatumumab, 5О2M-40, pertuzumab, EMO-273063, I19-1/-2 condensed protein, PEX-321 , SMTO-328,

MOXx-214, tigapotide, CAT-3888, labetuzumab, alpha-particle-emitting radioisotope-linked lintuzumab, EM-1421, NuregAshsche vaccine, tucotuzumab celmoleukin, galiximab, NRMU-16-E7, dameijp - prostate cancer, dameijp - melanoma . -CYTMT-1/8B Monoclonal antibodies suitable as protein therapeutics include, but are not limited to, the following: muromonab-COP, abciximab, edrecolamab, daclizumab, gentuzumab, alemtuzumab, ibritumomab, cetuximab, bevicuzumab, efalizumab, adalimumab, omalizumab, muromomab-COZ, rituximab, daclizumab, trastuzumab, palivizumab, basiliximab, and infliximab.

Compounds of the invention can also be combined with biological therapeutic agents such as antibodies (eg, Avastin, Rituxan, Erbitx, Herceptin) or recombinant proteins.

The compounds of the invention can also be combined with anti-angiogenic agents such as, for example, avastin, axitinib, UABT, recentin, sorafenib or sunitinib. Combinations with proteasome inhibitors or ttoOK inhibitors, or anti-hormones, or steroid metabolic enzyme inhibitors are also possible.

Typically, the use of cytotoxic and/or cytostatic agents in combination with a compound or composition of the present invention provides: (1) better efficacy in reducing tumor growth or even killing the tumor, compared to the separate administration of each agent, (2) administration of fewer chemotherapeutic agents, (3) providing a chemotherapeutic treatment that is well tolerated by the patient with fewer adverse pharmacologic complications compared to the administration of a single chemotherapeutic agent and other combination therapy, (610) (4) providing treatment for a wider range of different types of mammalian, especially human, cancers,

(5) increases the response rate among patients, (b) increases survival time among patients, compared with standard chemotherapy, (7) slows tumor growth, and/or (8) shows at least as good efficacy and tolerability results as when administered of the specified agents in the singular, in comparison with known cases where the use of a combination of other agents had an antagonistic effect.

Ways of sensitizing cells to radiation

In this embodiment of the present invention, the compound of the present invention is used to sensitize cells to radiation. That is, treatment of a cell with a compound of this invention before irradiation makes the cell more sensitive to DNA damage and cell death than in the absence of such treatment with a compound of the invention. In one aspect, the cell is treated with at least one compound of the invention.

Thus, the present invention also relates to a method of destroying a cell, where one or more compounds of the invention are injected into the cell in combination with standard radiation therapy.

The present invention also relates to a method of sensitizing a cell to cell death, wherein the cell is treated with one or more compounds of the invention, prior to treating the cell leading to cell death. In one aspect, after the cell is treated with one or more compounds of the invention, the cell is treated with at least one compound or at least one method, or a combination thereof, to damage DNA to inhibit normal cell function or kill the cell.

In one embodiment, the cell is killed by treating the cell with at least one

DNA damaging agent. That is, after treating the cell with one or more compounds of the invention to sensitize the cell to cell death, the cell is treated with at least one DNA damaging agent for cell death. DNA damaging agents useful in the present invention include, but are not limited to, chemotherapeutic agents (eg, cisplatin), ionizing radiation (X-rays, UV radiation), carcinogenic agents, and mutagenic agents.

In another embodiment, the cell is killed by treating the cell with at least one method to damage DNA. Such methods include, but are not limited to, activating a cellular signaling pathway that results in DNA damage when the pathway is activated, inhibiting a cellular signaling pathway that results in DNA damage when the pathway is inhibited, and causing a biochemical change in the cell where the changes lead to DNA damage. The DNA repair pathway can be inhibited in multiple ways, thus preventing DNA damage repair and abnormal damage accumulation

DNA in the cell.

In one aspect of the invention, the compound of the invention was introduced into the cell before irradiation or other damaging effect on the DNA of the cell. In another aspect of the invention, the compound of the invention was introduced into the cell simultaneously with irradiation or other damaging effect on the DNA of the cell. In another aspect of the invention, the compound of the invention was introduced into the cell immediately after the start of irradiation or other damaging effect on the DNA of the cell.

In another aspect, the cell is within my IP. In another variant of the embodiment, the cell is ip past.

As mentioned above, the compounds of this invention unexpectedly showed effective inhibition

Mre-1 and therefore can be used to treat or prevent diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses or inappropriate cellular inflammatory responses or diseases mediated by uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses or inappropriate cellular inflammatory responses, particularly where uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses or inappropriate cellular inflammatory responses mediated by Mp5-1, such as, for example, hematological tumors, solid tumors, and/or their metastases, such as leukemia and myelodysplastic syndrome, malignant lymphomas, head and neck tumors, including brain tumors and brain metastases, thoracic tumors, including non-small cell and small cell lung cancer, gastrointestinal tumors, endocrine tumors, breast tumors and others gynecologist gical tumors, urological tumors, including kidney, bladder and prostate tumors, skin tumors, and sarcomas, and/or their metastases.

According to another aspect thus, the present invention includes a compound of general formula I!, or a stereoisomer, tautomer, M-oxide, hydrate, solvate, or a salt thereof, in particular, a pharmaceutically acceptable salt thereof, or a mixture thereof, as described and defined herein document, for (610) use in the treatment or prevention of disease as specified above.

Another aspect of this invention relates to the use of a compound of the general formula | described above, or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or its salt, in particular, its pharmaceutically acceptable salt, or a mixture thereof, for the prevention or treatment of a disease.

Another aspect of the present invention relates to the use of a compound of the general formula I described above for the preparation of a pharmaceutical composition for the treatment or prevention of a disease.

The diseases referred to in the previous two paragraphs are diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses or inappropriate cellular inflammatory responses or diseases mediated by uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses or inappropriate cellular inflammatory responses, particularly where uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, or inappropriate cellular inflammatory responses mediated by Mp5-1, e.g., hematological tumors, solid tumors, and/or their metastases, e.g., leukemia and myelodysplastic syndrome, malignant lymphomas, head and neck tumors, including brain tumors and brain metastases, chest tumors, including non-small cell and small cell lung cancer, gastrointestinal tumors, endocrine tumors, breast tumors and other gynecological tumors, urological and tumors, including kidney, bladder and prostate tumors, skin tumors, and sarcomas and/or metastases thereof.

The term "inappropriate" in the context of the present invention, particularly in the context of "inappropriate cellular immune responses or inappropriate cellular inflammatory responses" as used herein, preferably means a response that is less than or greater than normal and that is associated with, responsible for, or results in to the pathology of the specified disease.

Preferably, use in the treatment or prevention of diseases where the diseases are hematological tumors, solid tumors and/or their metastases.

Method of treatment of hyperproliferative disorders

The present invention relates to a method of using a compound of the present invention and compositions thereof for the treatment of hyperproliferative disorders in mammals. The compounds can be used to inhibit, block, reduce, decrease, etc., cell proliferation and/or cell division, and/or induce apoptosis. This method includes administering to a mammal in need, including a human, a certain amount of a compound of the present invention or its pharmaceutically acceptable salt, isomer, polymorph, metabolite, hydrate, solvate or ester; that are effective in treating the disorder. Hyperproliferative disorders include, but are not limited to, for example, the following: psoriasis, keloidosis, and other hyperplasias affecting the skin, benign prostatic hyperplasia (BPH), solid tumors such as breast cancer, respiratory tract, brain, reproductive organs, stomach -intestinal tract, urinary tract, eyes, liver, skin, head and neck, thyroid gland, parathyroid gland and their isolated metastases. These diseases also include lymphomas, sarcomas, and leukemia.

Examples of breast cancer include, but are not limited to, invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma of the 5th grade, and lobular carcinoma of the 5th grade.

Examples of respiratory tract cancers include, but are not limited to, small cell and non-small cell lung carcinoma, as well as bronchial adenoma and pleuropulmonary blastoma.

Examples of brain cancer include, but are not limited to, brainstem and hypoophthalmic glioma, cerebellar and cerebellar astrocytoma, medulloblastoma, ependymoma, and neuroectodermal and pineal tumor.

Male genital tumors include, but are not limited to: prostate and testicular cancer. Tumors of the female genital organs include, but are not limited to, endometrial cancer, cervical cancer, ovarian cancer, vaginal and vulvar cancer, and uterine sarcoma.

Gastrointestinal tumors include, but are not limited to, anal cancer, colon cancer, colorectal cancer, esophageal cancer, gallbladder cancer, stomach cancer, pancreatic cancer, rectal cancer, small bowel cancer, salivary gland cancer. Urinary tract tumors include, but are not limited to, bladder, penile, kidney, renal pelvis, ureter, urethral, and human papillary renal cancers.

Eye cancers include, but are not limited to, intraocular melanoma and (610) retinoblastoma.

Examples of liver cancer include, but are not limited to, hepatocellular carcinoma (carcinoma of liver cells with or without fibrolamellar variant), cholangiocarcinoma (carcinoma of intrahepatic bile ducts), and mixed hepatocellular cholangiocarcinoma.

Skin cancer includes, but is not limited to, squamous cell carcinoma, Kaposi's sarcoma, malignant melanoma, Merkel cell carcinoma, and non-melanoma skin cancer.

Head and neck cancer includes, but is not limited to, laryngeal cancer, hypopharyngeal cancer, nasopharyngeal cancer, oropharyngeal cancer, lip and oral cavity cancer, and squamous cell cancer.

Lymphomas include, but are not limited to, AIJUb-associated lymphoma, non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, Burkitt's lymphoma, Hodgkins' disease, and lymphoma of the central nervous system.

Sarcomas include, but are not limited to, soft tissue sarcoma, osteosarcoma, malignant fibrous histiocytoma, lymphosarcoma, and rhabdomyosarcoma.

Leukemia includes, but is not limited to, acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, and squamous cell leukemia.

These disorders have been well characterized in humans, but also exist with similar etiologies in other mammals, and can be treated by administration of the pharmaceutical compositions of the present invention.

The term "treatment" or "treatment" as used herein refers to, for example, the management or care of a patient for the purpose of combating, mitigating, reducing, alleviating, ameliorating, etc., a disease or disorder such as carcinoma.

Methods of treating kinase disorders

The present invention also relates to methods of treating disorders associated with aberrant mitogenic extracellular kinase activity, including, but not limited to, heart attack, heart failure, hepatomegaly, cardiomegaly, diabetes, Alzheimer's disease, cystic fibrosis, xenograft rejection, septic shock, or asthma.

An effective amount of a compound of the present invention is used to treat such disorders, including diseases (eg, cancer) described in the background of the invention section above. However, such cancers and other diseases can be treated with the compounds of this invention regardless of the mechanism of action and/or relationship between the kinase and the disorder.

The phrase "aberrant kinase activity"? or "aberrant tyrosine kinase activity," include any abnormal expression or activity of a gene encoding a kinase or polypeptide.

Examples of such aberrant activity include, but are not limited to, overexpression of a gene or polypeptide; gene amplification; mutations providing constitutively active or hyperactive kinase activity; gene mutations, deletions, substitutions, additions, etc.

The present invention also relates to methods of inhibiting kinase activity, especially mitogenic extracellular kinase, which include the administration of an effective amount of a compound of the present invention, including its salts, polymorphs, metabolites, hydrates, solvates, prodrug forms (eg: esters), and diastereoisomeric forms thereof. Kinase activity is inhibited in cells (e.g., human immunodeficiency virus) or mammalian cells, especially human cells, in need thereof.

Methods of treatment of angiogenic disorders

The present invention also relates to methods of treating disorders and diseases associated with excessive and/or abnormal angiogenesis.

Unacceptable and ectopic expression of angiogenesis can be harmful to the body. There is a certain number of pathological conditions associated with the growth of foreign blood vessels. These include, for example, diabetic retinopathy, ischemic retinal vein occlusion, and retinopathy of prematurity. Meme/ Epoi. U. May. 1994, 331, 1480; Reeg ey ay. And ar. Ipmevi 1995, 72, 638), muscle degeneration associated with age (|AMO; z5eee, I ore?ei a. Ipmevzi. Oripia!toi.

Mib5. All together. 1996, 37, 855), neovascular glaucoma, psoriasis, retrolental fibroplasia, angiofibroma, inflammation, rheumatoid arthritis (RA), restenosis, restenosis in a stent, restenosis of a vascular graft, etc. In addition, increased blood supply to cancer-related and non-plastic tissues accelerates growth, which leads to rapid tumor growth and metastases. Moreover, the growth of new blood and lymphatic vessels in the tumor provides an escape route for foreign cells, which increases metastases and spreads the cancer. Thus, the compounds of this invention are used to treat and/or prevent any of the above (610) disorders of angiogenesis, for example, by inhibiting and/or reducing the rate of blood vessel formation; by inhibiting, blocking, reducing, reducing, etc., the proliferation of endothelial cells or other cells participating in angiogenesis, and also using cell death or apoptosis of these types of cells.

Dosage and administration

Based on standard laboratory techniques for the evaluation of compounds suitable for the treatment of hyper-proliferative disorders and angiogenic disorders, using standard toxicity tests and standard pharmacology studies to determine the treatment of the above conditions in mammals, and by comparing these results with those of known drugs that are used to treat these diseases, effective dosages of the compounds of the present invention can easily be determined for the treatment of each desired condition. The amount of active ingredient administered to treat one of these conditions can vary considerably depending on the particular compound and dosage form used, the route of administration, the time of treatment, the age and sex of the patient, and the nature and importance of the condition being treated.

The total amount of active ingredient administered is usually in the range of from about 0.001 mg/kg to about 200 mg/kg of body weight per day, and preferably from about 0.01 mg/kg to about 20 mg/kg of body weight per day. The dosage schedule usually ranges from 1 to 3 times a day to once every four weeks. In addition, "vacation from medication" when the patient is not administered medication for a certain period of time can have a beneficial effect on the overall balance between pharmacological effect and tolerability. A single dose may contain from about 0.5 mg to about 1500 mg of active ingredient, and may be administered one or more times per day or less than once per day. The average daily dose for injections, including intravenous, intramuscular, subcutaneous and parenteral injections, and infusions is preferably 0.01-200 mg/kg of total body weight. The average daily rectal dose is preferably 0.01-200 mg/kg of total body weight. The average daily vaginal dose is preferably 0.01-200 mg/kg of total body weight. The average daily local dose is preferably 0.1-200 mg from 1 to 4 times a day. The transdermal concentration is preferably sufficient to maintain a daily dose of 0.01-200 mg/kg. The average daily dose for inhalation is preferably 0.01-100 mg/kg of total body weight.

Of course, the specific initial and subsequent dosage regimens are determined for each patient individually, and depend on the nature and severity of the condition as determined by the doctor, the activity of the specific compound used, the age and general condition of the patient, the time of administration, the route of administration, the rate of excretion of the drug, the combination of drugs, etc. The preferred route of treatment and dosage amount of a compound of the present invention or a pharmaceutically acceptable salt or ester or composition thereof is determined by the skilled artisan using standard tests.

Preferably, the diseases of the specified method are hematological tumors, solid tumors and/or their metastases.

The compounds of this invention are used in particular in the treatment or prevention, i.e. prevention of tumor growth and metastases, especially solid tumors of all indications and stages with or without prior treatment of tumor growth.

Methods for testing certain pharmacological or pharmaceutical properties are well known to those skilled in the art.

The examples of test experiments described in this document serve to illustrate this invention, and the invention is not limited to the given examples.

Biological analysis: proliferation analysis

Cultured tumor cells (MCE7, human hormone-dependent breast carcinoma cells, ATOS NTV22; MCI-H460, human cells of non-small cell lung carcinoma, ATOS

NTVv-177; BO 145, human cells of hormone-dependent carcinoma of the prostate, ATCC NTV-81;

Ne a-MaTy, human cervical carcinoma cells, ERO-StrnN, Vetpipe; Ne a-MaTi-AOV, human cells of cervical carcinoma, resistant to drugs, ERO-StrbnN, Vepiip; human cervical carcinoma cells Not a, ATCC SS -2; B16E10 mouse melanoma cells,

ATOSS SVI -6475) were seeded at a density of 5000 cells/well (МСЕ7, БО145, Ней а-Маты-АОН), 3000 cells/well (МСИ-Н460О, Неі а-МаТы, Не а) or 1000 cells/well (В16Е10) in a 96b-well microtitre plate in 200 μl of their respective growth medium supplemented with 10 95 fetal calf serum. After 24 h, the cells of one plate (null plate) were stained with crystal violet (see below), while the medium of the other plates was replaced with fresh culture medium (200 μl) to which the test compound was added at various concentrations (0 μM and also in the range 0.01-30 μM; the final concentration of the dimethyl sulfoxide solvent was 0.5 95). Cells were incubated for 4 days in the presence of test compounds. Cell proliferation was determined by crystal violet staining of cells: cells (610) were fixed by adding 20 μl/point of measurement of 11 95 glutaraldehyde solution for

15 min. at room temperature. After three cycles of washing the fixed cells with water, the tablets were dried at room temperature. Cells were stained by adding 100 μl/point of measurement of 0.1 95 solution of crystal violet (pH 3.0). After three cycles of washing the stained cells with water, the tablets were dried at room temperature.

The dye was dissolved by adding 100 μl/point of measurement of 10 9o acetic acid solution.

The optical density was measured by photometry at a wavelength of 595 nm. The change in the number of cells, in percent, was calculated by normalizing the measured values to the values of the optical density of the null plate (-0 95) and the optical density of untreated (0 μm) cells (-100 95). IC5O values were determined using 4 parameters using the company's own software.

Analysis of Mr5-1 kinase

Human kinase Mr5-1 phosphorylates a biotinylated peptide substrate. Detection of the phosphorylated product is carried out using resonance fluorescence energy transfer with time division (TK-EKT) from a europium-labeled anti-phospho-serine/h-threonine antibody as a donor to streptovidin labeled with cross-linked allophycocyanin (5A-XI ep) as an acceptor . The compounds were tested for inhibition of kinase activity.

M-terminal 55T-labeled human unprocessed recombinant Mr5-1 kinase (manufactured by Ipmigodep, Karlsruhe, Germany, MO RU4071) was used. As a substrate for the kinase reaction, a biotinylated peptide with the amino acid sequence RU/YUROBAVITEII C was used (C-end in amide form, manufactured by Viozupipap SITnH, Berlin).

For the analysis, 50 nl of a 100-fold concentrated solution of the test compound in OM5O was added with a pipette to a black 384-well microtiter tablet with a small volume (Sgeipeg Vio-Ope,

Egpiskeppaizep, Germany), 2 μl of the solution of Mr5-1 in the analysis buffer | added 0.1 mM sodium ortho-vanadate, 10 mM Mosi», 2 mM OTT, 25 mM Nerez pH 7.7, 0.05 95 B5A, 0.001 95 RiIshgopis

E-127| and the mixture was incubated for 15 min. at 22 "C for preliminary binding of test compounds with Mpo5-1, before the start of the kinase reaction. Then the kinase reaction was started by adding 3 μl of a solution of 16.7 adenosine tri-phosphate (ATP, 16.7 μM -" final conc. in 5 μl of the analyzed volume was 10 μM) and the peptide substrate (1.67 μM -» the final conc. in 5 μl of the analyzed volume was 1 μM) into the analyzing buffer, and the resulting mixture was incubated for 60 min. at 22 " WITH. The concentration of Mp5-1 in the assay was adjusted relative to the activity of the enzyme lot and selected to obtain assays in the linear range, the usual enzyme concentrations were approximately 1 nM (final conc. in 5 μl of the analyzed volume). The reaction was stopped by adding 3 μl of a solution of NTEE detector reagents (100 mM Nerez pH 7.4, 0.1 95 VBA, 40 mM EOTA, 140 nM zigeriamidine-XI epi (Zh 61251 XI B, Ra. Siv

Violiip(egpaiopa!, Magsotschier, France|, 1.5 nM anti-phospho(zZeg/TPg)-Europium-antibody |ЖА0О180,

RekipEIteg G A5, Vodaai-Uydespeit, Germany|.

The resulting mixture was incubated for an hour at 22 "C to bind the phosphorylated peptide to the anti-phospho(Zeg/Tpg) europium-antibody. Then the amount of phosphorylated substrate was calculated using resonance fluorescence energy transfer from europium-labeled anti-phospho(zZeg/Tpg) antibodies to streptavidin-HiI epi Therefore, the fluorescence emission at 620 nm and 665 nm after excitation at 350 nm was measured in a Mieuli TE-EKET reader (RegkipEITeg

IA5, Voddaiy-Uydespeijt, Germany). The "control-corrected normalized ratio" (a Mieulich-specific reading similar to the traditional ratio of emissions at 665 nm and at 622 nm, where the mutual noises of the control and the europium donor were subtracted from the signal at 665 nm before calculating the ratio) was taken as the unit of measure for the amount of phosphorylated substrate. The data were normalized (enzymatic reaction without inhibitor - 0 95 inhibition, all other components of the analysis without enzyme - 10095 inhibition). The test compound was studied on the same microtiter plate at 10 different concentrations in the range of 20 μM-1 nM (20 μM, 6.7 μM, 2.2 μM, 0.74 μM, 0.25 μM, 82 NM, 27 NM, 9 , 2 nM, 3.1 nM and 1 nM, dilution series were prepared from 100 times the concentration of the mother solution in 1:3 dilution series) with repetition for each concentration and IC5O values were calculated by 4 parameters using proprietary software.

Unexpectedly, it was found that the inhibitory activity of compounds of the general formula | the presence of KU, which means an aryl-X or heteroaryl-X group, has a positive effect.

Therefore, compounds of the general formula I, above, where KZ means an aryl-X or heteroaryl-X group, are preferred.

Table 1 2 805 | g 332 pava

ЕВ ЕС хв ва им ж s ни S SK in 273 | KO Ty kl gy (2! 37 | Ye ke

Table 1 (continued)

An example of TM! | "The example of Yimrvi

PoBOINMI | | its there

MA BO | it? aa pen ny nie nyn styattyat nn (MV 12 | TVA («07 rukh tt kofayattnia stat o V--n- I -- t 4. '- - - - -- -k« 52 32 ! 773B (38 en nn, -ХХ-- 4: "Ch-I---

VZ ti 74. "07 kri poshi ET U 54 78 | (75 ih and 55 2 | 78 (507

B "10 77 "07

Mia t Ya |, liny mon 57 aa | (78 102 g58 20.5 | 78 07 (59 325 | 80 02 ptn sho: pidi tt kAAATYANTYa KB-V- 5yu5 5 | «5 tt vo 102 | gv1 02 ov io | iv 03 : panna v Se t ya ( vaA 02 | VZA 02 titration of routines (biv oz: vav 98 en nn Pn en b2A 02 | "va oz v2v 5 | "V 02 53 i«0 | i 86 v va oz | iv? 02 pomnnnnnnn zinnn vin nn 65 07 ! and you are mine!!

Who am I?

Table 1 (continued)

Example |Mrv! | (Example |Mrei peBoM Duvotnmi 7 Tv3 -- thank you

EN be | ie sled ropes Kosy svia 48 WITHOUT | 494 at:

EY Tv yayu a bot av 002o SHY o gav | 128 at I

Capacity 8800 sq. m. 132 KY

KASH E SY Mi KE HNN la to kan shn ram

PSY ET 136 To vro kyu 300020 | 135 dm er vv kshshEh lsh nyny V s pl nyny S vaz SHHI 144 023

Pen University

Table 1 (continued)

Example Sea! | "Shelter Mr: ! i . | ; . psBoInM| S PSBOINMI (147 22 | 172 08 148 15 173 od 149 22 174 "by tvo KI 475 kA Y vi KE | itvyavvo S 152 33 | 77 82 tva (36 | 178 o tva (25o | 179 VMO 38 | (1vo mod

H 1 156 gwi | /181 395.9 in? (12.0 | r1vo m

Penn plyny psy ti syst nin 1 148 | 184 1010 180 tower vom and (181 652 | I186 vzvo 2 gvya, 8? 49, 183 305 | 1v8 m 154 63 189 g 185 v | theo Tvoy ve 53 | I tet 200000. 167 23 i2 000215 188 oz | 493 la

Ge Gol | 194 28

Go 07 | 1195 32 17 ov 1196 27 I

Table 1 (continued) of annuities

Example | Languages | | Prykpad | Dreams

SHY sBOinMI. | | | isBognMI rt rtknia grain rony 187 "1.0 g225 (in? rents in min ZOV OO 168 28 hav iz 199 va (227 02 "200 M (228 Iov :201 3 | 299 2.6 shi shin o 202 15 (230 12 groz 14 (231 14.3 oo «1 232 (to ! pen now WE other she

G 208 i727 | 233 1 and sha vshiinnn "call 82 234 iv !

Kent vne re V Ya (207 village (235 82 208 20 (236 Gm "209 08 237 vv ' mo 89 nn S opy wines to wash or pan g Ba (239 885 2 «to | (go 18 23 «10 | mA M 214 o div 34 215 7 (a 37 (cha 10 | :243 rehe t za | gad b yiv 037 | 245 07 , gu a im ! I zav ov (229 Im ! 1247 117

Inna yam um puttya yamu frontit titi tm here - 22 48 zav v

Quantity (222 (2 | 249 02 223 02 (25 Gaz pet Den (224 (ho 15 |02

Table 1 (continued) arable rent

Example "Mr! | "Example Mr pevognMI ; SBONMI zva 02 vv 10 (253 oz ste chav

Hotinettchniayat t-2Ш2--- rony poshi vm ony kozh (255 02 2vi oz

There is Ys2 | 282 I (257 4 04 283 10.3 ' ry nyti y t 2Ba 02 zva od : (259 oz | 285 4 zvo 02 | (286 (oA anna niny I nn they peni

Govi | 05 | 287 03! 2 0 : : more :

OTC ana vom (283 |za Y (289 (02 4 svia 20 280 oz vet yi -- i i « x fen peki a (285 | 08 | zvov pes pozi Bony vo

ED they NI zi sleep (2nd century Kene | G294A io

ЖМЖ- - Yes - --I5 -4 -- - 4-5 1 6 o 2 Ci nn nn nn nn nn nn

KZ Toz | 2848102

Si VA dya 000 houses at times. lines only 5,272 more | 29бА |05 пикання renttenuttyuttrettttattya 23105 | | ghev 4 0.5 274 re av 02 nn ol on wn 275 54 | (297 hom 276 (ol | eVA «o 2t7 I vav vm

TVA M 299 va

Table 1 (continued) about (8 S X U

Oz01 02 (324 oz I

Melon rin - YAMU

В0а оз | 325 th fitntnnnnnnnaya hllkhlylldilthkhchhhhhhhchkhhychanh EB----T

ZOZA m | 897

For information on the present Betinnen V I "disruption 01 329 "p / 305 06 | 33002 call Tov EN EK: В 307 05 | 332 | 288

Gzov o 333 vv an p oon po nn "Zoo M M -Z3a Zoo

And 4 ziinchnigts.. | Ben IS TL Ya

From m | 335 links

From og | 335 and 312 02 | 337 38 kn he u in 313 01 | "338 v3a for 02 | 339 959

From lake | Z4o 33

B--7--- ECU

ZI in by! (106

M? 74 | 342 (in that (643 343143: (319 KRON for 00930 zga for | zav (Zo I

KN about | for 16,302,708 | (instead of Koch. -- "2 " L A A -

ZBV

Table 7 (continued) point nn and zav 15 g zvo pom 349 04 ! zvi (ov el niv kny zni it N ruts sleep --7 o'clock 55 08: For your vehicle 356 96

EE | Mon

He is responsible for getting it (360 (08 | zv Ken vva tya

For r03 and | ZO. Oh yeah, I'm on floor 36! 02 and ! For the 1st-3rd volya zva 02 ryh fen pf sent zav a | 395 Goa zv MORE | (call ve "zav Gol 396 oz razvy connnnnny PO nn nn 389 Io | (897 10 rt tet E- 9 4; " 2 - 2 - 2 5 -2 - -x

Г370 (vl 38 04 pon nn eta 87 (92 | 399 gom I nennlmnnnnnny must mountains I 372 02 400 for 373 02 401 then (374 Go3 | 402 for lush rune until

Sleep, we dream, SN, Gv; | yeah

PLUM m wines million (377 (0.3 405 02 378 02 g406 04 37 (02 | 409 07

Table 1 (continued)

Bash va in 82000 gave -x 418 12 | ava oz lysa 452. -i8

I ge 459.04 43 (by | 466 48 432 48 | 487 18

Table 1 (continued) system 03000016 left | 5o8 and the seams are all with I shi or NI 483.01 | 52 o lish ne S Y SS m sly sslysh knys sny MY sa mon 4802 sh viv vy o nty i s Х

El zlv va 3 SOSHENY

KY Sst and SY SU VYN

You are S EE about the sea

FIGHTS gom | /53O ov veva vim

Table 1 (continued)

BM (ol vva 0 ov 8535 (by | sBBI 02 '838 oz | v? 0.2 vk 03 vka 01070

What are the | : code ; nn nn E day vzV Hour | gBBA in 53a ba | vv warm kn par (540 Go | 558 them: va 04 | 557 22 "vaz (vy | 558 oz fon et pon pi vaz 00002 Y ve ov "Bai pa | 5850 homm min ren ropy UCHI gBaB Io 4 vv Goe mm zh t shi ny nyny nyin 1547 | 02 | : I : mon en ne

BAV (07 vav (02 zv2

Table 1

Example |Mrei Shadow of Mrei

ISBO NM) | PSO NMI

El U 597 or yam "580 "10 |/606 ME

BV REK 807 she

BI 00695000 eV ex TI

In the above table, Mi was not tested

Spindle assembly control point analysis

The division spindle assembly checkpoint ensures correct segregation of chromosomes during mitosis. Upon entry into mitosis, chromosomes begin to condense, which is accompanied by phosphorylation of histone NZ on serine 10. Dephosphorylation of histone NZ on serine 10 begins in anaphase and ends at the beginning of telophase. Accordingly, phosphorylation of histone NZ on serine 10 can be used as a marker of cells in the state of mitosis. Nocodazole is a compound that destabilizes microtubules. Thus, nocodazole interferes with microtubule dynamics and mobilizes the spindle assembly checkpoint.

Cells are arrested in mitosis at the C2/M transition and exhibit phosphorylated histone NZ at serine 10. Inhibition of the spindle assembly checkpoint with Mp5-1 inhibitors reverses the mitosis block in the presence of nocodazole, and cells complete mitosis prematurely. Such a change is manifested by a decrease in cells with phosphorylated histone NZ on serine 10. Such a decrease is used as a marker to determine the ability of a compound of the present invention to cause a failure of mitosis.

Cultivated cells of the human cervical cancer cell line NeGa (ATSS SS -2) were seeded at a density of 2500 cells/well in a 384-well microtiter plate in 20 μl of Dulbecco's medium (m/o. phenol red, m/o. sodium pyruvate, (m.) 1000 mg/ml glucose, (m.) pyridoxine) supplemented with 1 95 (0./0.) glutamine, 1 9o (0./0.) penicillin, 1 9o (0./0.) streptomycin and 10 95 (0./0.) calf embryo serum. After overnight incubation at 37 "C, 10 μl/well of nocodazole was added to the cells at a final concentration of 0.1 μg/ml. After 24 hours of incubation, the cells were arrested at the cell cycle phase (32/M. Test compounds dissolved in dimethyl sulfoxide (OM50O), was added in different concentrations (0 μM, as well as in the range of 0.005 μM - 10 μM; the final concentration of the OM5O solvent was 0.5 95 (0./0.)). The cells were incubated for 4 hours at 37 "C in the presence of test compounds. After that, the cells were fixed in 4 95 (0.70. paraformaldehyde in phosphate buffered saline solution (PB5) at 4 "C overnight, then infiltrated in 0.1 905 (0./0.) Top XTM 100 in PB5 at room temperature for 20 min and blocked in 0.5 95 (0./0.) calf serum albumin (B5A) in RVZ at room temperature for 15 min. After washing with RV5, 20 μl/well of antibody solution (anti-phospho -histone NZ clone ZNI10, RITS; Oreiaie, Ca 16-222; dilution 1:200) was added to the cells, which were incubated for 2 hours before and room temperature. After that, the cells were washed with PB5 and 20 μl/well of NOESH5T 33342 dye solution (5 μg/ml) was added to the cells, and the cells were incubated for 12 min. at room temperature in the dark. Cells were washed twice

PB5, then PB5 was added and stored at 4 "C until the start of the analyses. Images were obtained on a Regkip EItag ORECATM Nidnp-Sopiepi Appaiubie geadeg reader. Images were analyzed with the MeiaChrge5z55 TM image analysis software manufactured by Moiessiah demise5, using the cell cycle module. In this analysis both labels were measured

NOESH5TT 33342 and phosphorylated histone NZ on serine 10. NOESH5TT 33342 DNA labels were used to count the number of cells. Staining of phosphorylated histone NZ on serine 10 determines the number of mitotic cells. Inhibition of Mr5-1 reduces the number of mitotic cells in the presence of nocodazole, indicating an incorrect course of mitosis. Raw assay data were further analyzed using four-parameter logistic regression analysis to determine IC50 values for each test compound.

For a person skilled in the art, assays for other Mr5 kinases can be performed similarly using appropriate reagents.

Thus, the compounds of the present invention effectively inhibit one or more Mpo5-1 kinases and are therefore useful for the treatment or prevention of diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses or inappropriate cellular inflammatory responses, particularly where uncontrolled growth cell proliferation and/or survival, inappropriate cellular immune responses or inappropriate cellular inflammatory responses are mediated by Mp5-1, more particularly where diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses or inappropriate cellular inflammatory responses are hematological tumors, solid tumors and/or their metastases, such as leukemia and myelodysplastic syndrome, malignant lymphomas, head and neck tumors, including brain tumors and brain metastases, thoracic tumors, including non-small cell and small cell lung cancer, gastrointestinal tumors, endocrine tumors , breast tumors and other gynecological tumors, urological tumors, including kidney, bladder and prostate tumors, skin tumors, and sarcomas, and/or their metastases.

Study of the metabolic stability of rat hepatocytes (including the calculation of hepatic IP after blood purification (SI)

Hepatocytes of Nap UmMmyziag rats were isolated using 2-stage perfusion. After perfusion, the liver was carefully removed from the rat: the liver capsule was opened and the hepatocytes were gently shaken into a Petri dish with ice-cold UUME. The obtained cell suspension was filtered through sterile gauze in a 50 ml Taisop tube and centrifuged at 50 x d (610) for 3 min. at room temperature. The cell pellet was resuspended in 30 ml of M/ME and centrifuged with a Regsoib grant twice at 100 x 494. Hepatocytes were washed again with Williams E medium (UMMME) and resuspended in a medium containing 595 EC5.

Cell viability was determined by trypan blue exclusion.

To study the metabolic stability of the liver, cells were distributed in M/ME containing 5,956 EC5 in glass flasks at a density of 1.0 x 106 viable cells/ml. The test compound was added to a final concentration of 1 µM. During the incubation, the hepatocyte suspension was constantly mixed and aliquots were taken at 2, 8, 16, 30, 45 and 90 minutes, to which an equal amount of cold methanol was immediately added. Samples were frozen at -20" C overnight, then centrifuged for 15 minutes at 3000 rpm and the supernatant was analyzed by the Addiepi 1200 NR'G C system with LCMS/MS detection.

The half-life of the test compound was determined from the concentration-time graph. From the half-life period, internal clearance was calculated, along with additional parameters of hepatic blood flow, the number of liver cells ip mimo and ip migo. Hepatic IP, blood clearance (CI) and maximum oral bioavailability (Hmax) were calculated. The values of the following parameters were used: hepatic blood flow - 4.2 l/hour/kg rat; the specific weight of the liver is 32 g/kg of the rat's body weight; liver cells ip mimo - 1.1 x 108 cells/g liver, liver cells ip migo - 0.5 x 106/ml.

It was unexpectedly discovered that the metabolic stability of a compound of the general formula is positively affected by the presence of at least one of the groups 2? and Bs, which is not a hydrogen atom.

For example, the replacement of a hydrogen atom for Ks or 2" by methyl increases the metabolic stability by 700 95 (Table 2a) or 177 95 (Table 25), respectively.

Therefore, in the preferred embodiment, Ka, B", dis and La mean, independently of each other, hydrogen or a halogen atom, or -CM, C:-Cv-alkyl, Ci-Cv-alkyl, halo-Ci-Cv -alkyl, halo-Ci-Ci-Alkoxy-, Nea(Bev)M-Ci-Ci-Alkyl, HO-Ci-Ci-Alkyl, MO-Ci-Ci-Alkyl, Ci-Ci-Alkoxy-Ci-Ci- alkyl, halo-C1-C1-Alkoxy-C1-C1-Alkyl-; provided that at least one of the BK groups" and Ks is not a hydrogen atom.

Table 28: Table 20: p and Bach | and I Etakh ryklad Structure | Chlrikpad truktuva More

United Nations | | va ni OO nnshsh chi

IS

KE, I | :

E и И | C is Shi Shi Shi Ku! ras dl koe u re, 463 AND MORE; | | aa g | ; во ( и и и вы 22 з ее (З ши | Ta ke ! nesvo: БШИ | о Mb

She | ше: ше | | - ! | in :

What?

And I and what | ' | book

NOSHII sya rai wa Yi vo efe; Yad, ak shiti re ve | obi vi zu Z o

Mk | ! i sya ry: A-kn i ; | 6 ev about them | ! this one

NIKY MON NIK NNYA NAONNNNN POHN won MAC

Unexpectedly, it was found that the presence of at least group B has a positive effect on the metabolic stability of the compound of the general formula (Tables 3a, 3b and 3c). For example, replacement

4-tetrahydropyranil for K? (compound of Example 323) to 1,1,1-trifluoroethyl (compound of Example 80) increases the metabolic stability by 81 95 (Table 3a).

Table Za ee Poetesa ke TE EE EE ee z. "Wormwood - p r pet

And | and Etah Y is | Etah! report Structure | ! Shiryklad (Structure Y I and | ruktur (che | | | ruktu you and also: | sho SHI what | v she r | ne dn | | u. | !

M j | | Shchi 333 t BOYU te still vyy and Z | MK 40 p Sh! | | Czech | : i : 4 | | | in, but! | | | их их | | and n pi po p po Y pon pon nannya m shi she

Now Aries

N CHE E in dk Shk and i vky in in me a i same

Owls tm Ve Vb | from 89 there is | | | what

Hikchyah A! what | howled ' in she she she | she shi shk shshishishshshshshny . E 5.

Mn and st sy 92 and Fe »

A, th 48

I'm shhhhhh!

Table Zb table Zo r ry rt

And what Etah shi tah

Example Structure | Example Structure ' !

That)! Se nn shi chne she penetttttnnnia yati shchi E i i : Ve | | vah : o 1 : and S rev | H both oyboeyu i chi and v16 TE | 390 th

SKU 89 | dyn vv

Each Role t | N

Хо АХ и Х я : и z-В | shi obkhgu! oh E | not nn nn ni I oon I sha and t | "MN "Mn | | go i i 56 And oboi zai | and

Дю в Ку я ! sk you yo M i. a: sht tka! and and E sr ! | iy I Ho i

Ho pn an i

S: TV! ; -k Y ; ! for x |! their and r

E "KE sna -x 538 St"

M zok re 57 uv, vi yin

It was unexpectedly discovered that the metabolic stability of the compound of the general formula is positively affected by the presence of K-.

For example, replacing cyclopropyl for KK? substituted cyclopropyl, such as 1-methylcyclopropyl, increases metabolic stability by 34 95 (Table 4).

Table 4 "Example Etah

Structure 5

Gee! ak owls

Zo oi ve i o as: ; who doesn't their roOzh b sa 481 Do o ra. 75 neck: NO

Oh and that's it

Her"

It was unexpectedly discovered that the metabolic stability of the compound of the general formula is positively affected by the presence of K?.

For example, replacing cyclopropyl for K2 with a noncyclic alkyl significantly increases metabolic stability.

Claims (1)

FORMULA OF THE INVENTION 1. The compound of the general formula I: in? nothing Dod k M A de: A means ra ra N Ge Ж Ж rai U M AD ra 4 des her 4 NM» 2 de or y y: ;, or rrla vla y o y V: U iii, res -zy to NM. 2 and НМ is or where " indicates the place of attachment of the indicated groups to the molecule; 2 means -С(-О)М(Н)В: or -С(-5)М(Н)В, or a group selected from: bt-8Ekh to M- steering wheel Gn in | more a M i I shk shi what Shk still che v? M / in dm MAK in their | v? v? | - | x | v? where " indicates the place of attachment of the specified groups to the molecule; IN? means a hydrogen atom or C-Cv-alkyl, halogen-Ci-Cv-alkyl, Nea(Be)M-C-Cv-alkyl, HO-C.1-Cv-alkyl, -C1-Cv-alkyl-CM, Si -Ci-Ci-Ci-Ci-alkyl, halogen-Ci-Ci-Ci-Ci-Ci-Ci-Ci-Alkyl, C2-Ci-Alkenyl-, CiCi-Ci-Alkynyl- or Ci-Ci-cycloalkyl-; where the specified C3-Cv-cycloalkyl- is optionally substituted, identically or differently, with 1, 2, C or 4 groups selected from the following: halogen, - OH, -CM, Ci-Cv-alkyl, Ci-- C1-Alkoxy-, halogen-C1-C1-alkyl-; BZ means aryl-xX- or heteroaryl-x-; where the indicated aryl-X- or heteroaryl-xX- is optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 B" groups; Bl: means hydrogen; B means hydrogen; one of the B groups ? and D"c represents a hydrogen atom, while the other represents a group selected from: halogen-, -CM, -OH, C1-C8-alkyl- and C1-C8-alkyl-; B" means a hydrogen atom or C:-Cv-alkyl, -"CHn)p-C2-Cv-alkenyl, -"(CHn)p-C2-Cv-alkynyl, -(SiHg)t-C3-Cv-cycloalkyl, -(CHg)t-(3-7-ene heterocycloalkyl), aryl-Si-Cv-alkyl, heteroaryl-C1-Cv-alkyl, halogen-C1-Cv-alkyl, Nea(Heu)M-C1-Cv- alkyl, HO-C.:-Cv-alkyl, -C1-Cv-alkyl-CM, Ci-Cv- alkoxy-Ci-Cv-alkyl, halogen-Ci-Cv-alkyl-Ci-Cv-alkyl, Cz-Cv -cycloalkyl, 3-7-membered heterocycloalkyl, C2-C8-alkenyl-, C1-C8-cycloalkenyl-, Co-C8-alkynyl-, aryl- or heteroaryl-; where C1-Cv-alkyl, -"CHn)p-C2-Cv-alkenyl, -"CHn)p-C2-Cv-alkynyl, -"CHn)t-C3-Cv-cycloalkyl, -"(CHn)t -(3-7-membered heterocycloalkyl), aryl-Ci-Cv-alkyl, heteroaryl-Ci-Cv-alkyl, halogen-C1-Cv-alkyl, Nea(Neu)M-C1-Cv-alkyl, HO-C: -Cv-alkyl, -Ci-Cv-alkyl-CM, C--Cv-Alkoxy-Ci-Cv-alkyl, Halogen-Ci-Cv-Alkoxy-C1-Cv-Alkyl, C3-Cv-cycloalkyl, 3-7 --linen heterocycloalkyl, C4-C6-cycloalkenyl-, aryl- or heteroaryl- are optionally substituted, identically or differently, by 1, 2, C or 4 BZ-groups; VU, Vba, dej. Dbs mean, independently of each other, a hydrogen atom or C1-C8-alkyl, HO-C1-C8-alkyl, C3-C8-cycloalkyl, Co-C8-alkenyl-, 3-7--ene heterocycloalkyl, aryl-, heteroaryl -, aryl-C1-C1-alkyl- or heteroaryl-C:-C1-alkyl-; B" means hydrogen or a halogen atom, or HO-, -CM, Ci-Cv-Alkoxy-, Ci-Cv-Alkyl, Halogen-C1-Cv-Alkyl, Nea(Neu)M-C1-Cv-Alkyl, HO- C.1-Cv-alkyl, C-Cv-Alkoxy-C1-Cv-Alkyl, halogen-Ci-Cv-Alkoxy-C1-Cv-Alkyl, Cg2-Cv-alkenyl, 3-7-ene heterocycloalkyl, aryl- , heteroaryl-, -С(-0)Н5, - С(-О)М(Н)АВа, -С(-О)М(Неа)Ве, -С(-0)0-Н5, -М(Нба )ne", -MO", -M(H)C(-O)Ne, -M(Neg)C(-O)Ne, - M(H)C(-OM(NVa)Nev, -M(Neg )О(-О)М(Нба)Нев, -М(Н)С(-О)ОНе, -М(Нег)О(-0)ОНе, -Ж(Н)Б(-О)Н, - M (Нбс)5(-0)Н8, -М(Н)Б(-О0)2Н?, -М(Нег)В(-0)2Нб, -М-5(-О)(Нба)ВЯ", - ОНе, -О(0-0)НЕ, (- О(С-О)М(Нта)Бе», -О(0-0)ОНе, -58Я, -5(-0)85, -5(- 0О)3М(Н)ВЯ, -5(-0)М(НЯ)АеБ, -5(-0)2Н85, - 5(-О2М(Н)Бе, -5(-0)2М(892)ВЭ? or -5(-0)(-М 852); where the indicated C-Cv-alkoxy-, aryl- or heteroaryl- are optionally substituted, identically or differently, by 1, 2 or 3 C-Cv-alkyl-, C-Cv-alkyl-, halogen-C1-Cv -Alkoxy-, -C(/-0)0-HE or -OH- groups; or, when two B'-groups are in the ortho-position to each other on an aryl or heteroaryl ring, these two B'-groups together form a bridge: МН", where " means the point of attachment of the specified aryl or heteroaryl ring; ВУ? means hydrogen or a halogen atom, or -CM, Ci-Cv-Alkoxy-, Ci-Cv-alkyl, halogen-Ci-Cv-alkyl, Vea(Ve )M-Ci-Cv-alkyl, HO-Ci-Ci-Cv-alkyl, C1-Ci-Alkoxy-Ci-Ci-Alkyl, Halogen-Ci-Ci-Ci-Alkoxy-Ci-Ci-Alkyl, Co-Ci-Alkenyl -, C3-7-ene heterocycloalkyl, aryl-, heteroaryl-, -С0(-0)Н6б - С(-О)М(Н)АВа, -С(-О)М(Неа)Бей, -С( -0)0-Н5, -М(Нба)не», -МО», -М(Н)С(-О)Не, -М(Нег)С(-О)Не, - М(Н)С( -OM(NVa)Nev, -M(Neg)O(-O)M(Nba)Nev, -M(Н)С(-О)ОНе, -М(Neg)О(-0)ОНе, -Ж( Н)Б(-О)Н, - M(Н5С)5(-О)НЯ, -М(Н)Б(-О0)2Н5, -М(Нбг)Б(-0)2Н6, -М-5( -0О)(Нба)ВЯ», -ОН8Я, -О(0-0)Н6, /(- О(С-О)М(Нта)Ве», -О(0-0)ОНе, -58Я, - 5(-0)85, -5(-0О)3М(Н)ВЯ, -5(-0)М(НЯ)АеБ, -5(-0)2Н85, - 5(-О2М(Н)Бе, - 5(-0)2M(892)Be», -5(-0(-MAe2)BE or -5(50)2-(3-7-membered heterocycloalkyl); where the indicated 3-7-ene heterocycloalkyl- or heteroaryl- is optionally substituted, identically or differently, by 1, 2, C or 4 C/-Cv-alkyl-; t means an integer 0, 1, 2, 3, 4, 5 or 6; n means an integer 0, 1, 2, 3, 4 or 5; X means 5(-О)р, О, МАЕ, СВбаВе» or С-Sinbade; p means an integer 0, 1 or 2; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof. 2. Compound according to claim 1, where B? is selected from the group consisting of the following: Ci-Cv-alkyl, halogen-Ci-Cv-alkyl, Nea(Be»)M-C1-Cv-alkyl, HO-C:-Cv-alkyl, -C1-Cv- alkyl-CM, C1-Cv- alkoxy-C1-Cv-alkyl, halogen-C1-Cv- alkoxy-Ci-Cv-alkyl, Co-Cv-alkenyl-, Co-Cv-alkynyl-; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof. 3. Compound according to any of claims 1-2, where B? means a hydrogen atom or C.i-Cv-alkyl, halogen-Ci-Cv-alkyl, HO-C:-Cv-alkyl, C3-Cv-cycloalkyl, 3-7-membered heterocycloalkyl or heteroaryl-; specified C-Ci-alkyl, halogen-Ci-Ci-alkyl, HO-Ci-Ci-alkyl, C3-Ci-cycloalkyl, 3-7-membered heterocycloalkyl, heteroaryl are optionally substituted, identically or - different, 1, 2, C or 4 B8-groups; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof. 4. A compound according to any one of claims 1-3, where B" means a halogen atom or HO-, -CM, C-Cv-alkoxy-, C-Cv-alkyl, halogen-C1-Cv-alkyl, HO-C -- Cn-alkyl, NeaM-Ci-Cn-alkyl, Cg2-Cn-alkenyl, 3-7/-membered heterocycloalkyl, -C(-0O)M(H)NYa, - M(Bba)Be», -« M(H)C(-O) A? or -585; where the indicated C-C-Alkoxy- or 3-7--ene heterocycloalkyl- is optionally substituted, identically or differently, by 1, 2 or 3 C -Ci-alkyl-, Ci-Ci-Alkoxy-, halogen-Ci-Ci-Alkoxy-, - C(-0)0O-HE or -OH-groups; or when two H'-groups are in the ortho-position to each other on an aryl or heteroaryl ring, the indicated two B'-groups together form a bridge: "bnu"СНггмМн"У, "Сн nМ(Бе)СНнг", "С(Н)-С(Н)-С(-0 )-M(NU, where " means the point of attachment to the specified aryl or heteroaryl ring; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or its salt, or a mixture thereof. 5. A compound according to any of claims 1-4, where VU, Vba, de and Des mean, independently of each other, a hydrogen atom or C-Cv-alkyl-; or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof. 6. The compound according to claim 1, which is selected from the group consisting of the following compounds: M-cyclopropyl-4-16-((2-methoxyphenyl)sulfanyl)|-8-((3,3,3-trifluoropropyl)amino| imidazo(|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, (85)-M-cyclopropyl-2-methyl-4-18-(4-methylmorpholin-2-yl)umethyl|amino)-6 - (phenylsulfanyl)imidazo|1,2-b|pyridazin-3-yl|renzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(4-hydroxyphenyl)sulfanylimidazo |1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(4-methoxyphenyl)sulfanilyimidazo|1,2 - 10) BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-((3-hydroxyphenyl)sulfanylimidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl -4-/8-((2-hydroxy-2-methylpropyl)amino|-6-((3-methoxyphenyl)sulfanilyimidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-((4-hydroxy-3-methylphenyl)sulfanyl/|-8-(2-hydroxy-2-methylpropyl)amino|midazo|1,2-b|Ipyridazin-3-yl)u -2-methylbenzamide, M-cyclopropyl-4-76-((5-fluoro-2-methylphenyl)sulfanyl|-8-(2-hydroxy-2- methylpropyl)amino|midazo|1,2-b|Ipyridazine-3 -yl)y-2-methylbenzamide, M-cyclopropyl-4-16-((4-fluoro-3-methylphenyl)sulfanyl|-8-(2-hydroxy-2- methylpropyl)amino|midazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-16-((3-fluoro-4-methylphenyl)sulfanyl|-8-(2- hydroxy-2-methylpropyl)amino|midazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-76-((3-fluoro-5-methylphenyl)sulfanyl|-8 -(2-hydroxy-2-methylpropyl)amino|midazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-16-((3,5-difluorophenyl)sulfanyl)|-8-K2-hydroxy-2-methylpropyl)amino|midazo|1,2-b|Ipyridazin-3-yl)y-2- methylbenzamide, M-cyclopropyl-4-16-((4-fluoro-2-methylphenyl)sulfanyl|-8-(2-hydroxy-2-methylpropyl)amino|midazo|1,2-b|Ipyridazin-3-yl) y-2-methylbenzamide, M-cyclopropyl-4-16-(2-fluorophenyl)sulfanyl/|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-((4-fluorophenyl)sulfanyl|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3 -yl)-2-methylbenzamide, M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-(2-hydroxyphenyl)sulfanilyimidazo|1,2- BIpyridazin-3-yl)- 2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(2-methoxyphenyl)sulfanilyimidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl- 4-(6-(3-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b|pyridazin-3-yl).2-methylbenzamide, M-cyclopropyl-4- /8-((2-hydroxy-2-methylpropyl)amino|-6-phenoxyimidazo|1,2-b|pyridazin-3-yl)-2- methylbenzamide, M-cyclopropyl-2-methyl-4-y16-phenoxy-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)benzamide, 4-y8-K2 -amino-2-methylpropyl)amino|-6-(3-fluorophenyl)sulfanylimidazo|1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-76-((3-fluoro-5-methylphenyl)sulfanyl|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2 -methylbenzamide, M-cyclopropyl-4-76-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)y-2-methylbenzamide , M-cyclopropyl-4-16-(2-fluoro-5-methylphenoxy)-8-|((2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-(6-(3-cyanophenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-p|pyridazin-3-yl)- M-cyclopropyl-2-methylbenzamide, (85)-M-cyclopropyl-4-/6-((3-fluorophenyl)sulfinyl|-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-76-((3-fluorophenyl)sulfonyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M- cyclopropyl-2-methyl-4-/6-(phenylsulfanyl)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-ylbenzenecarbothioamide, 4-(6-(3z-chlorophenoxy) )-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-M- cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(4-methoxyphenoxy)imidazo|1,2- BIpyridazin-3-yl)-2- methylbenzamide, M-cyclopropyl-4-76-(3-fluoro-5-methylphenoxy)-8-|((2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2- methylbenzamide, M-cyclopropyl-4-76-(3-fluoro-5-methylphenoxy)-8-I((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-((3-fluorophenyl)sulfanyl|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-( 6-(4-chlorophenoxy)-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-M- 10) cyclopropyl-2-methylbenzamide, 4-(6-(3-chloro-4-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide , M-cyclopropyl-4-16-(-2,3-difluorophenoxy)-8-|((2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-(6-(2-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazin-3-yl).2-methylbenzamide, M-cyclopropyl -4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(3-isopropylphenoxy)imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-(6-(4 -chloro-3-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)aminoyl|imidazo|1,2-b|pyridazin-3-yl)-M- cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-/6-(3,5-dimethylphenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazoi|1,2- BIpyridazin-3-yl)-2 -methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(3-methylphenoxy)imidazo|1,2-b|pyridazin-3-yl).2-methylbenzamide , M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(quinolin-5-yloxy)imidazo|(1,2-b|Ipyridazin-3-yl).2-methylbenzamide , M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(quinolin-6-yloxy)imidazo|(1,2-b|Ipyridazin-Z-yl).2- methylbenzamide, M-cyclopropyl-2-methyl-4-/6-(quinolin-6-yloxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-ylbenzamide, M-cyclopropyl-2-methyl-4-/6-(quinolin-5-yloxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazine-3 -ylbenzamide, M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-3-yloxy)imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide , M-cyclopropyl-2-methyl-4-16-(pyridin-3-yloxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-ylbenzamide, M-cyclopropyl- 2-methyl-4-18-(2-methylpropyl)amino|-6-(phenylsulfanyl)imidazo|1,2-p|Ipyridazin-3-yl)benzamide, M-cyclopropyl-2-methyl-4-18-( 2-methylpropyl)amino|-6-(phenylsulfonyl)imidazo|1,2-p|Ipyridazine-3- yl)benzamide, M-cyclopropyl-2-methyl-4-/6-(phenylsulfanyl)-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2- BIpyridazin-3-ylbenzamide, M-cyclopropyl -4-76-((3-fluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-2-methyl-4-/6-(phenylsulfonyl)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-ylbenzamide, M-cyclopropyl-4-/ 8-((2-hydroxy-2-methylpropyl)amino|-6-«(phenylsulfanyl)imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-76-((Z- fluorophenyl)sulfanyl|-8-((3,3,3-trifluoro-2- hydroxypropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-16-(2,6-difluorophenyl)sulfanyl)|-8-K2-hydroxy-2 - methylpropyl)amino|midazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-/6-(2-methoxyphenoxy)-8-((3,3,3- trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-16-((2-hydroxyphenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)aminoimidazol|1,2-BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4 -76-(3-methoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-/ 6-((4-methoxyphenyl)sulfanyl)|-8-((3,3,3-trifluoropropyl)amino|imidazo(|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-|((3-hydroxyphenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)aminoimidazo|1,2- BIpyridazin-3- yl)-2-methylbenzamide, M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino |-6-(4- (trifluoromethyl)phenyl|sulfanyl)imidazo|1,2-b|pyridazine- 3-yl)-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-phenoxyimidazo|1,2-p|pyridazin-3-yl)benzenecarbothioamide, M-cyclopropyl-4-/6-( 3-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b|pyridazine-3-ylbenzenecarbothioamide, M-cyclopropyl-4-/8-((2-hydroxy-2- methylpropyl)amino|-6-"(phenylsulfanyl)imidazo|1,2- (610) BIpyridazine-3-ylbenzenecarbothioamide, M-cyclopropyl-4-16-((3-fluorophenyl)sulfanyl|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-ylbenzenecarbothioamide, M-cyclopropyl-2-methyl- 4-(6-C4-"trifluoromethyl)phenyl|sulfanyl)-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)benzamide, M-cyclopropyl-4-16-(2,5-difluorophenyl)sulfanyl)|-8-K2-hydroxy-2-methylpropyl)amino|midazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide . , M-cyclopropyl-4-76-((4-fluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-((3,5-difluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazine -3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-(2,3-difluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazine-3 -yl)-2-methylbenzamide, M-cyclopropyl-4-(6-(4-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)amino|imidazo|/1,2-b|pyridazin-3-yl).2-methylbenzamide, M- cyclopropyl-4-(6-(3,4-difluorophenoxy)-8-((2-hydroxy-2-methylpropyl)amino|imidazo(|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl -4-16-(2,5-difluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(4-isopropoxyphenoxy)imidazo|1,2- BIpyridazin-3- yl)-2-methylbenzamide, M-cyclopropyl-4-(6-(4-isopropoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2 -methylbenzamide, M-cyclopropyl-4-16-(-2,3-difluorophenoxy)-8-((3,3,3-trifluoropropyl)aminoyl|imidazo|(1,2-b|pyridazin-3-yl).2-methylbenzamide , M-cyclopropyl-4-16-(2-fluoro-5-methylphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-[6-(3,4-difluorophenoxy)-8-((3,3,3-trifluoropropyl)amino]|imidazo|(1,2-b|pyridazine- 3-yl).2-methylbenzamide, M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-(2-thienylsulfanyl)imidazoi|1,2- BIpyridazin-3-yl) -2-methylbenzamide, M-cyclopropyl-4-16-(3,5-difluorophenoxy)-8-|((2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2 -methylbenzamide, M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-((b-methylpyridin-3-yl)oxy|imidazo|1,2- BIpyridazin-3-yl)-2 -methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(pyrimidin-5-yloxy)imidazo|(1,2- BIpyridazin-3-yl)-2- methylbenzamide, 4-(6-(3-chlorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl-M-cyclopropyl- 2-methylbenzamide, 4-(6-(4-chlorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-16-(2-fluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-76-((5-fluoro-2-methylphenyl)sulfanyl|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2 -methylbenzamide, M-cyclopropyl-4-(6-C2-(hydroxymethyl)phenyl|sulfanyl)-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl )-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-((3-methoxy-phenyl)sulfanilyimidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-|(3-isopropylphenyl)sulfanylimidazo|1,2- BIpyridazin-3 -yl)-2-methylbenzamide, M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-2-yloxy)imidazo|!1,2-b|Ipyridazine- 3-yl).2-methylbenzamide, M-cyclopropyl-4-/6-I3-(2-hydroxy-2-methylpropoxy)phenoxy)|-8-((2-hydroxy-2-methylpropyl)amino|midazo|1,2-b|Ipyridazine-3- yl)y-2-methylbenzamide, M-cyclopropyl-4-/6-((3-fluorophenyl)sulfanyl|-8-((2-hydroxyethyl)amino|imidazo|(1,2-b|pyridazin-3-yl )y-2-methylbenzamide, M-cyclopropyl-4-76-(3-fluorophenoxy)-8-(2-hydroxyethyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-2- 10) methylbenzamide, M-cyclopropyl-4-(6-(2-hydroxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-p|pyridazin-3-yl)y-2-methylbenzamide, M -cyclopropyl-4-76-(3-fluorophenoxy)-8-((tetrahydro-2H-thiopyran-4-ylmethyl)aminoimidazol|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-[6-(3-fluoro-5-methylphenoxy)-8-|(tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl) γ-2-methylbenzamide, M-cyclopropyl-4-716-(2-fluorophenoxy)-8-((tetrahydro-2H-thiopyran-4-ylmethyl)aminoimidazol|1,2- BIpyridazin-3-yl)-2-methylbenzamide , M-cyclopropyl-2-methyl-4-/6-(phenylsulfanyl)-8-((tetrahydro-2H-thiopyran-4- ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-ylbenzamide, M-cyclopropyl-4-/6-((3-fluorophenyl)sulfanyl|-8-((tetrahydro-2H-thiopyran-4-ylmethyl )amino|imidazo|1,2-b|pyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-16-((3-fluoro-5-methylphenyl)sulfanyl|-8-Ctetrahydro-2H- thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-16-|(3-hydroxyphenyl)sulfanyl|-8-Ctetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y-2- methylbenzamide, M-cyclopropyl-2-methyl-4-16-(pyridin-3-yloxy)-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3 -ilibenzamide, M-cyclopropyl-4-16-((2-hydroxyphenyl)sulfanyl|-8-Ctetrahydro-2H-thiopyran-4- ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-716-(4-fluorophenoxy)-8-((tetrahydro-2H-thiopyran-4 -ylmethyl)aminoimidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-(6-(4-chloro-3-fluorophenoxy)-8-((tetrahydro-2H-thiopyran-4-ylmethyl)amino |imidazo|1,2-b|Ipyridazin-Z-yl)"M-cyclopropyl-2-methylbenzamide, 4-(6-(4-chlorophenoxy)-8-(tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, M -cyclopropyl-4-76-(-2,3-difluorophenoxy)-8-|(tetrahydro-2H-thiopyran-4-ylmethyl)amino|imidazoi|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4 -(6-(4-chlorophenoxy)-8-( | (cis/trans)-1-oxidotetrahydro-2H-thiopyran-4- yl|methyl)amino)imidazo|1,2-b|Ipyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, 4-(6-(4-chlorophenoxy)-8-1(1,1-dioxidotetrahydro- 2H-thiopyran-4-ylylmethylamino)imidazoi|1,2- BIpyridazin-3-yl|-Y-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-I6-(4-fluorophenoxy)-8-4|(cis/ trans)-1-oxidotetrahydro-2H-thiopyran-4-yl|methyl)amino)imidazo|1,2-b|Ipyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4-IV-4(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)umethyl|amino)-6-(4-fluorophenoxy)imidazo(1,2-b|pyridazin-3-yl| -2-methylbenzamide, M-cyclopropyl-2-methyl-4-18-((cis)-1-oxidotetrahydro-2H-thiopyran-4-yl|methyl)amino)-6-(pyridin-3-yloxy)imidazo| (1,2-b|Ipyridazin-3-yl|benzamide, M-cyclopropyl-2-methyl-4-18-Htrans)-1-oxidotetrahydro-2H-thiopyran-4-yl|Imethyl)amino)-6- (pyridine-3-yloxy)imidazo(1,2-b|pyridazin-3-yl|benzamide, M-cyclopropyl-4-I8-4(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)umethyl|amino )-6-(pyridin-3-yloxy)imidazo(1,2-b|Ipyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4-IV-4(1,1-dioxidotetrahydro-2H-thiopyran- 4-yl)umethyl|amino)-6-(2-fluorophenoxy)imidazo(1,2-b|pyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-4|(cis/trans)-1-oxidotetrahydro-2H-thiopyran-4-yl|methyl)amino)imidazo|1,2-b|Ipyridazine- 3-yl|-2-methylbenzamide, M-cyclopropyl-4-IV-4(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)umethyl|amino)-6-(3-fluorophenoxy)imidazo(1,2 -b|pyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4-16-((3,4-difluorophenyl)sulfanyl)|-8-K2-hydroxy-2- methylpropyl)amino|midazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-(8-((1,1-dioxidotetrahydro-2H-thiopyran-4-yl)umethylI |amino)-6-|(3-fluorophenyl)sulfanilyimidazo|1,2-b|Ipyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-I8-4(1,1-dioxidotetrahydro-2H-thiopyran -4-yl)umethyl|amino)-6-(phenylsulfanyl)imidazo|1,2-b|pyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-2-methyl-4-I8-((cis)-1-oxidotetrahydro-2H-thiopyran-4-yl|methyl)amino)-6-(phenylsulfanyl)imidazo|1,2-b|pyridazine-3 -yl|renzamide, M-cyclopropyl-2-methyl-4-18-Xtrans)-1-oxidotetrahydro-2H-thiopyran-4-yl|Imethyl)amino)-6- (phenylsulfanyl)imidazo|1,2-b| Pyridazin-3-yl|renzamide, M-cyclopropyl-4-(6-((3-fluorophenyl)sulfanyl|-8-4 (cis)-1-oxidotetrahydro-2H-thiopyran-4- (610) yl|methyl)amino)imidazo|1,2-b|Ipyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-(6-((3-fluorophenyl)sulfanyl|-8-C (trans)-1-oxidotetrahydro-2H-thiopyran-4-yl|methyl)amino)imidazo|1,2-b|Ipyridazine -3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-((4-fluorophenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl )-2-methylbenzamide, 4-(6-anilino-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-16- ((3,4-difluorophenyl)amino|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-/8 -((2-hydroxy-2-methylpropyl)amino|-6-((3-methylphenyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-76-((5-fluoro-2-methylphenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazoi|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-16-K4-chlorophenyl)amino|-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1,2-p|Ipyridazin-3-yl)- M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-16-(3-fluorophenoxy)-8-((1-methylpiperidin-4-yl)methylamino)imidazo(|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl- 4-I8-/T3-(dimethylamino)propyl|amino)-6-(3-fluorophenoxy)imidazo|1,2-b|pyridazin-3-yl|---methylbenzamide, M-cyclopropyl-4-I6-( 3-fluorophenoxy)-8-C2-(methylsulfonyl)ethyl|amino)imidazo|1,2-b|Ipyridazine- 3-yl|-2-methylbenzamide, 4-yl|8-K2-amino-2-methylpropyl)amino|-6-(3-fluorophenoxy)imidazo|(1,2-p|pyridazin-3-yl)-M-cyclopropyl -2-methylbenzamide, 4-i8-Casetidin-3-ylmethyl)amino|-6-phenoxyimidazo|1,2-b|Ipyridazin-3-yl-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(4H-1,2,4-triazol-3-ylsulfanyl)imidazo|1,2-b|Ipyridazine-3 -yl)y.2-methylbenzamide, M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino)-6-((4-methyl-1H-imidazol-2-yl)sulfanyl imidazo) ,2-b|pyridazin-3-yl/u.2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(1 H-imidazol-2-ylsulfanyl) )imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-(1-methyl-1H-pyrazol-5-yl)oxy| imidazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(4-(piperazine- 1-Iluphenoxy|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(1-methyl-1H-pyrazol-4-yl)oxy|imidazo|1,2-b|Ipyridazine-3 -yl)y-2-methylbenzamide, tert-butyl-4-(4-(13-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1, 2-b|Ipyridazin-b-ylyloxy)phenyl|piperazine-1-carbosylate, M-cyclopropyl-4-/6-(3-fluorophenoxy)-8-(tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo| 1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-/6-((3-fluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b| pyridazine-3-yl).2-methylbenzamide, M-cyclopropyl-4-[16-(3-fluorophenoxy)-8-((3-hydroxy-3-methylbutyl)amino|imidazo|!1,2-b|Ipyridazine - 3-yl).2-methylbenzamide, M-cyclopropyl-4-I8-4(1,1-dioxidotetrahydrothiophen-3-yl)umethyl|amino)-6-(3-fluorophenoxy)imidazo(1,2-b|pyridazin-3-yl|-2-methylbenzamide , M-cyclopropyl-4-[6-(3-fluorophenoxy)-8-(tetrahydrofuran-3-ylmethyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4 -16-(3-fluorophenoxy)-8-(Х((1-methyl-5-oxopyrrolidin-3-yl)umethylamino)imidazo(|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4-(8-1(3,3-difluorocyclobutyl)methyl|amino)-6-(3Z-fluorophenoxy)imidazo|1,2- BIpyridazin-3- yl|-2-methylbenzamide, M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-4-yloxy)imidazo|!1,2-b|Ipyridazine-Z -yl).2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-4-ylsulfanyl)imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M- cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-2-ylsulfanyl)imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-y8- K2-cyanoethyl)amino|-6-(3-fluorophenoxy)imidazo|1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2- 10) methylbenzamide, 4-16-K4-chloro-2-fluorophenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-p|Ipyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(5-methoxy-2-methylphenyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)u -2-methylbenzamide, M-cyclopropyl-4-16-((3,5-difluorophenyl)amino|-8-(2-hydroxy-2-methylpropyl)amino|imidazo(|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-(2,3-difluorophenyl)amino|-8-(2-hydroxy-2-methylpropyl)amino|imidazo(|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M -cyclopropyl-4-/6-((3-fluoro-4-methoxyphenyl)amino|-8-K2-hydroxy-2- methylpropyl)amino|midazo|1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(4 -methoxyphenyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-16-KZ-chlorophenyl)amino|-8-(2-hydroxy-2-methylpropyl)amino|imidazo(1, 2-[Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-16-(2,4-difluorophenyl)amino|-8-(2-hydroxy-2-methylpropyl)amino|imidazo(|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M -cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-2-ylamino)imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl -4-/6-((4-fluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazine- 3-yl).2-methylbenzamide, M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-3-ylamino)imidazo|1,2- BIpyridazine-3- yl)-2-methylbenzamide, M-cyclopropyl-4-16-(2-fluoro-4-methylphenyl)sulfanyl|-8-(2-hydroxy-2-methylpropyl)amino|midazo|1,2-b|Ipyridazine- 3-yl)y-2-methylbenzamide, M-cyclopropyl-4-(8-((2-hydroxy-2-methylpropyl)amino|-6-(3-isopropoxyphenoxy)imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl- 4-76-((2-fluoro-4-methylphenyl)sulfanyl|-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M -cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(pyridin-4-ylamino)imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-((b-methoxypyridin-3-ylamino|imidazo|1,2 -b|Ipyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-16-(2-fluoro-5-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo |1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-(6-anilino-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)y-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4 -/6-(2-fluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl).2-methylbenzamide, M-cyclopropyl-4- (6-C2-(hydroxymethyl)phenyl|amino)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-76-((3-fluoro-5-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo(|1 ,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-16-K4-chloro-3-fluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b| Ipyridazin-3-yl)-N-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-16-((3,4-difluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4 -16-K4-chlorophenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl -4-76-((5-fluoro-2-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-16-K4-chloro-2-fluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazine-3 -yl)-M-cyclopropyl-2-methylbenzamide, 4-16-Kb-chloro-2-methylphenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|/1,2-b|Ipyridazine -3-yl)-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-16-((3,5-difluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4 -16-KZ-chlorophenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl -4-16-(2,3-difluorophenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- 10) BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-2-methyl-4-16-3-(propan-2-yloxy)phenoxy|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3- ilibenzamide, M-cyclopropyl-4-16-((4-fluoro-3-methylphenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2- methylbenzamide, M-cyclopropyl-4-16-((2-fluoro-5-methylphenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-(2-fluorophenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4 -/8-((2-hydroxy-2-methylpropyl)amino|-6-|(3-isopropylphenyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-(6-C4-(2-hydroxyethyl)phenyl|amino)-8-K(2-hydroxy-2-methylpropyl)amino|midazo|1, 2-b|Ipyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-76-((3-fluoro-2-methylphenyl)sulfanyl|-8-((3,3,3-trifluoropropyl)amino| imidazo|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-((2-methoxyphenyl)amino1|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl -2-methyl-4-16-(2-(methylamino)phenoxy|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-ylbenzamide, M-cyclopropyl-4-16 -(5-fluoro-2-methylphenoxy)-8-I((3,3,3-trifluoropropyl)amino|imidazoi|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-76-(5-fluoro-2-methylphenoxy)-8-|((2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-(6-C4-chloro-2-(hydroxymethyl)phenyl|sulfanyl)-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2 - BIpyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, 4-(6-C4-chloro-2-(hydroxymethyl)phenyl|sulfanyl)-8-((2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-M-cyclopropyl- 2-methylbenzamide, M-cyclopropyl-4-16-((3-fluoro-5-methylphenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)- 2-methylbenzamide, 4-(6-(2-aminophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)-M- cyclopropyl-2-methylbenzamide, 4-(6-(2-amino-4-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)- M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-/6-((4-fluoro-2-hydroxyphenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazine -3-yl)-2-methylbenzamide, 4-(6-(2-chloro-3-fluorophenoxy)-8-(2-hydroxy-2-methylpropyl)aminoyl|imidazo|1,2-b|pyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide . )y-2-methylbenzamide, M-cyclopropyl-4-16-((2-hydroxyphenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-/6-((4-fluoro-3-methoxyphenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|midazo|1,2 -b|Ipyridazin-3-yl)y-2-methylbenzamide, 4-16-K4-chloro-3-fluorophenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-p| pyridazin-3-yl)"M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(2-methoxyphenyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M- cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-((3-methoxyphenyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4- 16-K5-chloro-2-methylphenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|Ipyridazine-3- yl)"M-cyclopropyl-2-methylbenzamide, 4-16-K2-chloro-4-fluorophenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazo|1,2-b|pyridazine-3- yl)"M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-16-|(b-fluoropyridin-3-yl)amino|-8-K2-hydroxy-2-methylpropyl)amino|imidazoi|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-/6-|((3-ethenylphenyl)amino|-8-K(2-hydroxy-2-methylpropyl)amino|imidazoi|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-/6-((b-fluoropyridin-3-yl)oxy|-8-(2-hydroxy-2-methylpropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2- methylbenzamide, 5-((3-(4-(cyclopropylcarbamoyl)-3-methylphenyl/|-8-K2-hydroxy-2-methylpropyl)amino|imidazoi|1,2- (610) BIpyridazine-6b-yloxy)nicotinamide, M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(pyrazin-2-ylsulfanyl)imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M- cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(4-methyl-4H-1,2,4-triazol-3-yl)usulfanyl imidazo|1,2-b|pyridazine -3-yl/y.2-methylbenzamide, M-cyclopropyl-4-[8-((2-hydroxy-2-methylpropyl)amino|-6-(1H-pyrazol-5-yloxy)imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide , M-cyclopropyl-4-/8-((2-hydroxy-2-methylpropyl)amino|-6-(5-methyl-1H-pyrazol-3-yl)oxy|imidazo|1,2-b|Ipyridazine- 3-yl)y-2-methylbenzamide, 4-16-K2-amino-4-fluorophenyl)sulfanyl|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazine-3- yl)"M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-/6-(2-methoxy-3-(propan-2-ylphenoxy|-8-(3,3,3- trifluoropropyl)amino|imidazo| (1,2-b|pyridazin-3-yl/y,2-methylbenzamide, M-cyclopropyl-2-methyl-4-16-(4-methyl-4H-1,2,4-triazol-3-yl) usulfanil|-8-K3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazine-3-ilybenzamide, M-cyclopropyl-2-methyl-4-16-(pyrazin-2-ylsulfanyl)-8-((3,3,3-trifluoropropyl)amino|imidazoi|1,2- BIpyridazin-3-ylbenzamide, M-cyclopropyl- 4-/6-((4-fluoro-3-methoxyphenyl)amino1|-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M -cyclopropyl-2-methyl-4-16-(3-methylphenyl)amino1|-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-ylbenzamide, M-cyclopropyl-4-/6-((3-fluoro-4-methoxyphenyl)amino1|-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazine- 3-yl)-2-methylbenzamide, M-cyclopropyl-4-/6-((4-methoxyphenyl)amino1|-8-(3,3,3-trifluoropropyl)amino|imidazo(1,2- BIpyridazine-3- yl)-2-methylbenzamide, M-cyclopropyl-4-16-((3-methoxy-2-methylphenyl)amino1|-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2- methylbenzamide, M-cyclopropyl-4-(6-C4-(2-hydroxyethyl)phenyl|amino)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)- 2-methylbenzamide, M-cyclopropyl-4-16-((4-fluoro-3-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazo(|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-|(b-methoxypyridin-3-yl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazoi|1,2 - BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-((5-methoxy-2-methylphenyl)amino1|-8-((3,3,3-trifluoropropyl)amino|imidazo|1 ,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-/8-(2-hydroxy-2-methylpropyl)amino|-6-(2-hydroxyphenyl)amino|imidazo(|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M- cyclopropyl-4-/6-((4-fluoro-2-methoxyphenyl)amino|-8-K2-hydroxy-2-methylpropyl)amino|midazo|1,2-b|Ipyridazin-3-yl)y-2- methylbenzamide, M-cyclopropyl-4-(6-C2-(hydroxymethyl)phenyl|amino)-8-((2-hydroxy-2- methylpropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-2-methylbenzamide, 4-(6-C4-(2-aminoethyl)phenyl|amino)-8-(2-hydroxy-2-methylpropyl )amino|imidazo|1,2-p|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-(6-((b-fluoropyridin-3-yl)oxy)|-8 -((3,3,3-trifluoropropyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-76-(2-fluoro-4-methoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M -cyclopropyl-4-16-|(b-fluoropyridin-3-yl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|(1,2- BIpyridazin-3-yl)-2-methylbenzamide , M-cyclopropyl-4-(6-(2-hydroxy-3-(propane-2-ylphenoxy)-8-((3,3,3- trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl/y.2-methylbenzamide, M-cyclopropyl-4-/6-((4-fluoro-3-hydroxyphenyl)amino|-8-( 3,3,3-trifluoropropyl)amino|imidazoi|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-|(5-hydroxy-2-methylphenyl)amino|-8- ((3,3,3-trifluoropropyl)amino|imidazoi|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-(2-fluoro-4-methoxyphenoxy)-8-|((tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo|(1,2-b|pyridazin-3-yl) y-2-methylbenzamide, M-cyclopropyl-4-(8-(2-hydroxy-2-methylpropyl)amino|-6-((3-hydroxyphenyl)amino|imidazo|1,2- BIpyridazin-3-yl)- 2-methylbenzamide, M-cyclopropyl-4-16-((3,4-difluorophenyl)amino|-8-K4,4,4-trifluorobutyl)amino|imidazo|1,2- 10) BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-(5-fluoro-2-methylphenyl)amino|-8-K4,4,4-trifluorobutyl)aminoimidazol|1,2-BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl -4-16-(3-fluoro-5-methylphenyl)sulfanyl|-8-(4,4,4-trifluorobutyl)amino|imidazo(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16-(2,3-difluorophenyl)amino|-8-K4,4,4-trifluorobutyl)amino|imidazoi|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-6 -(5-chloro-2-methylphenyl)amino|-8-K4,4 4-trifluorobutyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl -4-16-(3-fluoro-5-methylphenoxy)-8-(4,4,4-trifluorobutyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-(6--(cyclopentylamino)-8-((3,3,3-trifluoropropyl)aminoimidazo|1,2-b|Ipyridazin-3-yl)-M- cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-/6-|(3-hydroxy-2-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazoi|1,2- BIpyridazine- 3-yl)-2-methylbenzamide, 4-(6--(cyclopentyloxy)-8-I(3,3,3-trifluoropropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl -4-16-|(5-hydroxy-2-methylphenyl)amino|-8-((3,3,3-trifluoropropyl)amino|imidazoi|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M -cyclopropyl-4-16-(4-fluoro-2-methoxyphenyl)amino|-8-(4,4,4-trifluorobutyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-76-(2-fluoro-3-«(methylsulfanyl)phenoxy)|-8-K(2-hydroxy-2-methylpropyl)amino|midazo| 1,2-b|Ipyridazin-3-yl)y-2-methylbenzamide, 4-16-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazine -3-yl)-2-methyl-N-(1-methylcyclopropyl)benzamide, 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)-M-(1- methoxycyclopropyl)-2- methylbenzamide, M-(1-cyanocyclopropyl)-4-16-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-(6-((5-fluoropyridin-3-yl)oxy)|-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-(6-(2-amino-5-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazine- 3-yl)-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-2-methyl-4-16-(1,2,3,4-tetrahydroquinolin-8-yloxy)-8-|(3,3,3 - trifluoropropyl)amino|imidazo|(1,2-b|pyridazine-3-ilybenzamide, M-cyclopropyl-4-[6-(8-hydroxy-3,4-dihydroquinolin-1(2H)-yl)-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b |pyridazin-3-yl/[2-methylbenzamide, M-cyclopropyl-2-methyl-4-16-(2-oxo-1,2-dihydroquinolin-b-yl)oxy]-8-((3,3 ,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazine-3-ilybenzamide, M-cyclopropyl-2-methyl-4-16-(2-methyl-1,2,3,4-tetrahydroisoquinoline-5 -yl)oxy|-8-((3,3,3- trifluoropropyl)amino|imidazo|(1,2-b|pyridazine-3-ylbenzamide, M-cyclopropyl-2-methyl-4-16-(3-methylphenoxy)-8-((3,3,3-trifluoropropyl)amino |imidazo|1,2- BIpyridazin-3-ylbenzamide, M-cyclopropyl-4-/6-(4-methoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b| Ipyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl-4-76-(4-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)y-2-methylbenzamide, M- cyclopropyl-4-76-(2-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)y-2-methylbenzamide, M-cyclopropyl- 2-methyl-4-16-(2-methylphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-ylbenzamide, M-cyclopropyl-4-76-(33-fluoro-4-methoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl) -2-methylbenzamide, 4-(6-((4-(acetylamino)pyridin-3-yl|oxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin- 3-yl)-M-cyclopropyl-2-methylbenzamide, 4-(6-(2-amino-3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2- methylbenzamide, M-cyclopropyl-4-/6-((2-fluoro-b-hydroxyphenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazoi|1,2- BIpyridazin-3-yl)- 2-methylbenzamide, M-cyclopropyl-2-methyl-4-16-(4-methylphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- 10) BIpyridazin-3-ylbenzamide, M-cyclopropyl-4-/6-((4-fluoro-2-hydroxyphenyl)amino|-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2- methylbenzamide, M-cyclopropyl-4-/6-|(3-hydroxypyridin-4-yl)amino1|-8-((3,3,3-trifluoropropyl)amino|imidazoi|1,2- BIpyridazin-3-yl) -2-methylbenzamide, M-cyclopropyl-2-methyl-4-16-(1-phenylethenyl)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-ylbenzamide, M-cyclopropyl-4-16 -(3-fluoro-4-methoxybenzyl)-8-((3,3,3-trifluoropropyl)amino|imidazo(1,2- BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-16- (3-fluoro-4-methylbenzyl)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-16-(3-bromobenzyl)-8-I((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl) y-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-/6-(3-fluorophenoxy)-8-((3,3,3-trifluoro-2-hydroxypropyl)amino|imidazo|1,2- BIpyridazine -3-yl)-2-methylbenzamide, M-cyclopropyl-4-IV-C2-(dimethylamino)ethylamino)-6-(3-fluorophenoxy)imidazo|1,2-b|pyridazin-3-yl|---methylbenzamide, M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-((1-methyl-1 H-pyrazol-z-yl)methyl|amino)imidazo|1,2- BIpyridazin-3-yl|-2- methylbenzamide, M-cyclopropyl-4-76-(3-fluorophenoxy)-8-(01H-pyrazol-3-ylmethyl)amino|imidazo(1,2-b|pyridazine-3- yl)y-2-methylbenzamide, M-cyclopropyl-4-16-(3-fluorophenoxy)-8-((3-(hydroxymethyl)oxetan-3-yl|methyl)amino)imidazo|1,2- BIpyridazine-3 -yl|-2-methylbenzamide, M-cyclopropyl-4-(8-((2,3-dihydroxypropyl)amino|-6-(3-fluorophenoxy)imidazo|1,2-b|pyridazin-3-yl)u - 2-methylbenzamide, M-cyclopropyl-4-76-(3-fluorophenoxy)-8-(2-methoxyethyl)amino|imidazo|1,2-b|pyridazin-3-yl)-2- methylbenzamide, M-cyclopropyl-4-I8- /T3-(dimethylamino)-3-oxopropyl|Iamino)-6-(3-fluorophenoxy)imidazo|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4-I8--(4, 4-difluorocyclohexyl)methylamino)-6-(3-fluorophenoxy)imidazoi|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4-(6-(3-fluorophenoxy)-8-Coxetan-3z-ylmethyl)amino|imidazo|1,2-b|pyridazin-3-yl) -2- methylbenzamide, M-cyclopropyl-4-[6-(3-fluorophenoxy)-8-((1H-tetrazol-5-ylmethyl)amino|imidazo|(1,2-p|Ipyridazin-3-yl)y-2-methylbenzamide , M-cyclopropyl-4-IV-C2-(dimethylamino)-2-methylpropyl|amino)-6-(3-fluorophenoxy)imidazo|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4 -16-(3-fluorophenoxy)-8-C2-methyl-2-(morpholin-4-yl)propyl|amino)imidazoi|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4 -I6-(3-fluorophenoxy)-8-C2-(piperidin-1-yl)ethylamino)imidazo|1,2-b|pyridazine-3- yl|---methylbenzamide, M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-C2-(morpholin-4-yl)uethyl|amino)imidazo|1,2-b|Ipyridazin-3-yl| ---methylbenzamide, M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-C2-(4-methylpiperazin-1-yl)ethylamino)imidazo(|1,2- BIpyridazin-3-yl|-2- methylbenzamide, M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-C2-(pyrrolidin-1-yl)ethyl|amino)imidazo|1,2-p|pyridazin-3-yl|---methylbenzamide, M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-((3- Imethyl(methylcarbamoyl)amino|propyl)amino)imidazo|1,2-b|pyridazin-3-yl|-2-methylbenzamide, 4 -I(8-(2-(acetylamino)ethyl|amino)-6-(3-fluorophenoxy)imidazo|1,2-b|Ipyridazin-3-yl|-M-cyclopropyl- 2-methylbenzamide, M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-((3-(piperidin-1-yl)propyl|amino)imidazo|1,2-b|pyridazin-Z-yl|- 2-methylbenzamide, M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-(3-(morpholin-4-yl)propyl|amino)imidazo|1,2-b|pyridazin-3-yl|-- -methylbenzamide, M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-(3-(pyrrolidin-1-yl)propyl|amino)imidazo|1,2-p|pyridazin-3-yl|---methylbenzamide, M -cyclopropyl-4-I6-(3-fluorophenoxy)-8-((3-(methylsulfonyl)propyl|amino)imidazo|1,2- BIpyridazin-3-yl|-2-methylbenzamide, 4-I8-PZ-( acetylamino)propyl|amino)-6-(3-fluorophenoxy)imidazo|1,2-b|Ipyridazin-Z-yl|-M- 10) cyclopropyl-2-methylbenzamide, Z8o0 M-cyclopropyl-4-16-(3-fluorophenoxy)-8-(methylamino)imidazo|1,2-b|pyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4-16-(3-fluorophenoxy)-8-C2-(1H-tetrazol-5-yl)ethyl|amino)imidazo|1,2-b|pyridazin-3-yl|-2-methylbenzamide , M-cyclopropyl-4-18-(2,2-difluoroethyl)amino|-6-(3-fluorophenoxy)imidazo|(1,2-b|pyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4 -(8-Ch4-«(dimethylamino)butyl|amino)-6-(3-fluorophenoxy)imidazo|1,2-b|pyridazin-3-yl|---methylbenzamide, M-cyclopropyl-4-76-( 3-fluorophenoxy)-8-(2,2,2-trifluoroethyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-2- methylbenzamide, M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-C2-(1H-pyrazol-1-yl)ethyl|amino)imidazo|1,2-b|pyridazin-3-yl|---methylbenzamide , M-cyclopropyl-4-I6-(2,3-difluorophenoxy)-8-C2-(methylsulfonyl)ethyl|amino)imidazo|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4-16-(5-fluoro-2-methylphenoxy)-8-(C2-(methylsulfonyl)ethylamino)imidazo|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4 -I6-(3-fluoro-4-methoxyphenoxy)-8-DPC2-(methylsulfonyl)ethylamino)imidazo|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4-I6-(2- fluoro-4-methoxyphenoxy)-8-DPC2-(methylsulfonyl)ethylamino)imidazo|1,2- BIpyridazin-3-yl|-2-methylbenzamide, 4-[8-K2-amino-2-methylpropyl)amino|-6-(3,4-difluorophenoxy)imidazo|(1,2-p|pyridazin-3-yl) -M-cyclopropyl-2-methylbenzamide, 4-i8-K2-amino-2-methylpropyl)amino|-6-(4-chlorophenoxy)imidazo|1,2-b|Ipyridazin-3-yl)-M-cyclopropyl- 2-methylbenzamide, 4-[8-K2-amino-2-methylpropyl]amino|-6-(pyridin-3-yloxy)imidazo(1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, 4-( 6-(4-chlorophenoxy)-8-C2-(dimethylamino)ethylamino)imidazo|1,2-b|Ipyridazin-3-yl|-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-IV-C2- (dimethylamino)ethylamino)-6-(pyridin-3-yloxy)imidazo|1,2-p|pyridazine-3- yl|---methylbenzamide, M-cyclopropyl-4-I6-(3,4-difluorophenoxy)-8-C2-(dimethylamino)ethylamino)imidazoi|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M -cyclopropyl-4-I6-(2,3-difluorophenoxy)-8-((1-methylpiperidin-4-ylmethyliamino)imidazo(|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-2-methyl-4-18-((1-methylpiperidin-4-yl)umethylyl|amino)-6-(pyridin-3-yloxy)imidazo!1,2-b|Ipyridazin-3-yl| benzamide, M-cyclopropyl-4-I6-(2,3-difluorophenoxy)-8-(methylamino)imidazo|1,2-b|pyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4-I6-(3 ,4-difluorophenoxy)-8-(methylamino)imidazo|1,2-b|pyridazin-3-yl(|-2- methylbenzamide, M-cyclopropyl-4-16-(5-fluoro-2-methylphenoxy)-8-(methylamino)imidazo|1,2-b|pyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-2- methyl-4-(8-(methylamino)-6-(2-(methylamino)phenoxy|imidazo|1,2-b|pyridazin-3-yl)benzamide, M-cyclopropyl-4-/6-((2-hydroxyphenyl)(methyl)amino|-8-(methylamino)imidazo|1,2-b|Ipyridazin-3-yl-2-methylbenzamide, M-cyclopropyl-4- 16-((5-fluoropyridin-3-yl)oxy|-8-(methylamino)imidazo|1,2-p|Ipyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-I6-(2- fluoro-4-methoxyphenoxy)-8-(methylamino)imidazo|1,2-p|Ipyridazin-3-yl|-2- methylbenzamide, M-cyclopropyl-4-I6-(3-fluoro-4-methoxyphenoxy)-8-(methylamino)imidazo(|1,2-b|pyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4 -I6-(2,3-difluorophenoxy)-8-PC2-(morpholin-4-yl)ethyl|amino)imidazoi|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M-cyclopropyl-4-I6-(5-fluoro-2-methylphenoxy)-8-P2-(morpholin-4-yl)uethylamino)imidazo|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M- cyclopropyl-2-methyl-4-(6-(2-(methylamino)phenoxy|-8-T2-(morpholin-4-yl)ethylamino)imidazo|(1,2-b|pyridazin-3-yl)benzamide, M-cyclopropyl-4-(6-((2-hydroxyphenyl)(methyl)amino|-8-C2-(morpholin-4-yl)ethyl|amino)imidazo|1,2- 10) BIpyridazin-3-yl)-2-methylbenzamide, M-cyclopropyl-4-I6-(3,4-difluorophenoxy)-8-PC2-(morpholin-4-yl)ethyl|amino)imidazoi|1,2- BIpyridazin-3-yl|-2-methylbenzamide, M- cyclopropyl-4-(6-((5-fluoropyridin-3-yl)oxy|-8-T2-(morpholin-4-yl)ethyl|amino)imidazo|1,2- BIpyridazin-3-yl)-2- methylbenzamide, M-cyclopropyl-4-I6-(3-fluorophenoxy)-8-((1-methylazetidin-3-yl)methylIamino)imidazo|1,2-BIpyridazin-3-yl|-2-methylbenzamide, 4-I8-Casetidin -3-ylmethyl)amino|-6-(3-fluorophenoxy)imidazo|1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, M-cyclopropyl-4-I6-(2,3 -difluorophenoxy)-8-((1-methylazetidin-3-yl)methyliamino)midazo|1,2- BIpyridazin-3-yl|-2-methylbenzamide, 4-i8-Casetidin-3-ylmethyl)amino|-6-(-2,3-difluorophenoxy)imidazo|1,2-b|pyridazin-3-yl)-M - cyclopropyl-2-methylbenzamide, 4-i8-Casetidin-3-ylmethyl)amino|-6-(5-fluoropyridin-3-yl)oxy|imidazo|1,2-b|Ipyridazin-3-yl)-M- cyclopropyl-2-methylbenzamide, 4-8-Cazetidin-3-ylmethyl)amino|-6-(5-fluoro-2-methylphenoxy)imidazo|(1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, 4- and 8-KZ-aminopropyl)amino|-6-(3-fluorophenoxy)imidazo|1,2-b|Ipyridazin-3-yl)-M-cyclopropyl-2-methylbenzamide, 3-(13-(4-(cyclopropylcarbamoyl) -3-methylphenyl|-6-(3-fluorophenoxy)imidazo|1,2-b|pyridazine-8- yl)iamino)propane-1-sulfonic acid, 2-(13-(4-(cyclopropylcarbamoyl)-3-methylphenyl|-6-(3-fluorophenoxy)imidazo|1,2-b|pyridazine-8- ilyamino)ethanesulfonic acid, M-(1-cyanocyclopropyl)-4-16-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide, 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)-2-methylbenzamide, 4-(6- (3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-M,2-dimethylbenzamide, M-ethyl-4-(6- (3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo!1,2-b|Ipyridazin-3-yl)-2- methylbenzamide, 4-16-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)-M-isopropyl-2-methylbenzamide, 4-(6-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-2-methyl-M-(3,3, 3-trifluoropropyl)benzamide, 4-(6-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-2-methyl-M-(2,2, 3,3,3-pentafluoropropyl)benzamide, M-(2,2-difluoroethyl)-4-16-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|!1,2- b|Ipyridazin-3-yl).2-methylbenzamide, (6-(3-fluorophenoxy)-8-(3,3,3-trifluoropropyl)aminoI|imidazo|1,2-b|Ipyridazin-3-yl)- M-isobutyl-2- methylbenzamide, 4-(6-(4-chlorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)-M,2-dimethylbenzamide, 4-( 6-(4-chlorophenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo(1,2-b|Ipyridazin-3-yl-M-ethyl-2-methylbenzamide, 4-(6-(2-fluoro-4-hydroxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)-M,2-dimethylbenzamide, M-ethyl-4-(16-(2-fluoro-4-hydroxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-p|Ipyridazin-3-yl)y-2 -methylbenzamide, 4-I6-(3,4-difluorophenoxy)-8-C2-(morpholin-4-yl)ethyl|amino)imidazo|1,2-b|Ipyridazin-3-yl|-M,2- dimethylbenzamide, M,2-dimethyl-4-(6-(2-methylphenoxy)-8-PC2-(morpholin-4-yl)ethyl|amino)imidazo|1,2-b|pyridazin-3-yl|Senzamide, 4-(6-(4-methoxyphenoxy)-8-C2-(morpholin-4-yl)ethylamino)imidazo|1,2-b|Ipyridazin-3-yl|-N,2-dimethylbenzamide, 4-I6-(2-fluoro-4-methoxyphenoxy)-8-P2-(morpholin-4-yl)ethyl|amino)imidazo|1,2-b|Ipyridazin-3-yl|-M,2-dimethylbenzamide, 4-I6-(5-fluoro-2-methylphenoxy)-8-PC2-(morpholin-4-yl)ethylamino)imidazo|1,2-b|pyridazin-3-yl|-M,2-dimethylbenzamide, 4- (6-(3,4-difluorophenoxy)-8-(tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo|(1,2-b|Ipyridazin-3-yl)y- 10) M,2-dimethylbenzamide, M,2-dimethyl-4-(6-(2-methylphenoxy)-8-((tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo|1,2- BIpyridazine-3-ylibenzamid, 4-(6- (3-fluorophenoxy)-8-((tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)-M,2-dimethylbenzamide, 4-(6-(4-methoxyphenoxy)-8-((tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo(1,2-b|pyridazin-3-yl)y-M,2-dimethylbenzamide, 4 -(6-(2-fluoro-4-methoxyphenoxy)-8-(tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo|/1,2-b|pyridazin-3-yl)-N,2-dimethylbenzamide , 4-16-(5-fluoro-2-methylphenoxy)-8-(tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo|1,2-b|pyridazin-3- yl)-"M,2-dimethylbenzamide, 4-16-(3-fluoro-4-methoxyphenoxy)-8-(tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo|/1,2-b|pyridazine- 3-yl)-M,2-dimethylbenzamide, 4-16-(3,4-difluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl )-M,2-dimethylbenzamide, 4-(6-(3-fluorophenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-M,2-dimethylbenzamide, 4-(6 -(2-fluoro-4-methoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)-M,2-dimethylbenzamide, 4-(6 -(5-fluoro-2-methylphenoxy)-8-I((3,3,3-trifluoropropyl)amino|imidazo|(1,2-b|pyridazin-3-yl)-M,2- dimethylbenzamide, 4-(6-(3-fluoro-4-methoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)-M,2- dimethylbenzamide, 4-[8-K2,2-difluoroethyl)amino|-6-(3,4-difluorophenoxy)imidazo|1,2-b|Ipyridazin-3-yl)-M,2-dimethylbenzamide, 4- and 8-K2,2-difluoroethyl)amino|-6-(2-fluoro-4-methoxyphenoxy)imidazo|1,2-b|Ipyridazin-3-yl)-M,2-dimethylbenzamide, 4-16-( 2,3-difluorophenoxy)-8-(2-methoxyethyl)amino|imidazo|1,2-p|Ipyridazin-3-yl)-M,2-dimethylbenzamide, 4-(6-(3,4-difluorophenoxy)- 8-(2-methoxyethyl)amino|imidazo|1,2-p|Ipyridazin-3-yl)-M,2- dimethylbenzamide, 4-[8-K2-methoxyethyl)amino|-6-(2-methylphenoxy)imidazo|1,2-b|pyridazin-3-yl)-M,2-dimethylbenzamide, 4-(6-(2-fluoro -4-methoxyphenoxy)-8-(2-methoxyethyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-M,2-dimethylbenzamide, 4-16-(5-fluoro-2-methylphenoxy)-8-(2-methoxyethyl)amino|imidazo|1,2-b|pyridazin-3-yl)-M,2-dimethylbenzamide, 4-(6-( 3-fluoro-4-methoxyphenoxy)-8-(2-methoxyethyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-M,2-dimethylbenzamide, 4-8-(2-methoxyethyl)amino| -6-phenoxyimidazo(1,2-b|Ipyridazin-3-yl)-M 2-dimethylbenzamide, 4-I6-(3,4-difluorophenoxy)-8-C2-(morpholin-4-yl)ethylamino)imidazo|(1,2-b|pyridazin-3-yl|-M-ethyl-2-methylbenzamide, M -ethyl-2-methyl-4-(6-(2-methylphenoxy)-8-T2-(morpholin-4-yl)ethyl|amino)imidazo|1,2-b|pyridazin-3-yl|Schsenzamide, M -ethyl-4-(6-(4-methoxyphenoxy)-8-C2-(morpholin-4-yl)ethyl|amino)imidazo|(1,2-b|pyridazin-3-ylI|-2- methylbenzamide, M-ethyl-4-(6-(2-fluoro-4-methoxyphenoxy)-8-2-(morpholin-4-yl)ethylamino)imidazo(1,2-b|pyridazin-Z-yl|-2 -methylbenzamide, M-ethyl-4-(6-(5-fluoro-2-methylphenoxy)-8-C2-(morpholin-4-yl)ethylamino)imidazo|1,2-p|Ipyridazin-3-yl|- --methylbenzamide, M-ethyl-2-methyl-4-(8-P2-(morpholin-4-yl)ethylamino)-6-phenoxyimidazo|1,2-b|pyridazin-3-yl)benzamide, 4-(6-(3 ,4-difluorophenoxy)-8-(tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo(1,2-b|Ipyridazin-3-yl)y-M-ethyl-2-methylbenzamide, M-ethyl-2 -methyl-4-(6-(2-methylphenoxy)-8-((tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo(|1,2- BIpyridazin-3-ylbenzamide, M-ethyl-4-(6-(4-methoxyphenoxy)-8-|(tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo|1,2-b|pyridazin-Z-yl ).2-methylbenzamide, M-ethyl-4-(6-(2-fluoro-4-methoxyphenoxy)-8-(tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo|1,2- BIpyridazine-3- yl)-2-methylbenzamide, M-ethyl-4-(6-(5-fluoro-2-methylphenoxy)-8-(tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2-methylbenzamide , M-ethyl-4-(6-(3-fluoro-4-methoxyphenoxy)-8-(tetrahydro-2H-pyran-4-ylmethyl)amino|imidazo|1,2- BIpyridazin-3-yl)-2- methylbenzamide, M-ethyl-2-methyl-4-(6-(2-methylphenoxy)-8-(3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)benzamide, M-ethyl-4-(6-(2-fluoro-4-methoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)y-2 -methylbenzamide, M-ethyl-4-16-(5-fluoro-2-methylphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazin-3-yl)u -2-methylbenzamide, M-ethyl-4-(16-(3-fluoro-4-methoxyphenoxy)-8-((3,3,3-trifluoropropyl)amino|imidazo|1,2-b|pyridazine-3- yl)y-2-methylbenzamide, 4-y8-K2,2-difluoroethyl)amino|-6-(2-fluoro-4-methoxyphenoxy)imidazo|1,2-b|Ipyridazin-3-yl)-M-ethyl -2- methylbenzamide, 4- and 8-K2,2-difluoroethyl)amino|-6-(5-fluoro-2-methylphenoxy)imidazo|1,2-b|Ipyridazin-3-yl)-M-ethyl-2- methylbenzamide, 4-(6-(3,4-difluorophenoxy)-8-K2-methoxyethyl)amino|imidazo|1,2-b|Ipyridazine-3 -yl-M-ethyl-2-methylbenzamide, M-ethyl-4-16-(2-fluoro-4-methoxyphenoxy)-8-(2-methoxyethyl)amino|imidazo|1,2-p|pyridazine-3- yl)-2-methylbenzamide, M-ethyl-4-16-(5-fluoro-2-methylphenoxy)-8-(2-methoxyethyl)amino|imidazo|1,2-b|Ipyridazin-3-yl)-2 - methylbenzamide, M-ethyl-4-(6-(3-fluoro-4-methoxyphenoxy)-8-(2-methoxyethyl)amino|imidazo|1,2-p|pyridazin-3-yl)-2-methylbenzamide, or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or salt thereof, or a mixture thereof. 7. Pharmaceutical combination containing: - one or more compounds according to any of claims 1-6, or its stereoisomer, tautomer, M-oxide, hydrate, solvate, or its salt, in particular its pharmaceutically acceptable salt, or their mixture ; and - one or more agents selected from the following: a taxane such as Docetaxel, Paclitaxel or Taxol; an epothilone such as Ixabepilone, Patupilone or Sagopilone; Mitoxantrone; Prednisolone; Dexamethasone; Estramustine; Vinblastine; Vincristine; Doxorubicin; Adriamycin; Idarubicin; Daunorubicin; Bleomycin; Etoposide; Cyclophosphamide; Ifosfamide; Procarbazine; Melphalan; 5- Fluoruracil; Capecitabine; Fludarabine; Cytarabine; Aha-S; 2-Chloro-2'-deoxyadenosine; Thioguanine; an antiandrogen such as Flutamide, Cyproterone Acetate or Bicalutamide; Bortezomib; a platinum derivative such as Cisplatin or Carboplatin; Chlorambucil; Methotrexate and Rituximab. 8. The compound of the general formula Ia: in? Neodn /Fe in: schi A ;IIa where VZ and IV: are as defined for the compound of the general formula I in any of claims 1-6, and A" means ra Ge 45) ra 4 As where 7 means a point attachment of the specified group to the molecule; Na, B", Dis and B'YA are as defined for the compound of general formula I in any of claims 1-6, and 7" means a group selected from 3: -FC(-FOOH , -C(-5)0OH, -C(-0)0-(C1-Cv-alkyl) or -C(-5)0-(C1-Cv-alkyl). 9. The compound of the general formula IM: it is not 2 MN in M Am where A and B: are as defined for a compound of general formula I in any of claims 1-6, and VU means a leaving group. 10. Compound of the general formula MY: o! Dt Kk M Am where A and B: are as defined for the compound of general formula I in any of claims 1-6, and SU means an optionally protected MHe group or a leaving group.