ZA200607668B - Imidazole derivatives used as tafia inhibitors - Google Patents

Description

@® 1

IMIDAZOLE DERIVATIVES LJSED AS TAFIA INHIBITORS

The invention relates to novel compounds o¥ the formula | which inhibit the enzyme

TAFla (activatted thrombin-activatable fibrinolysis inhibitor), to process fer their preparation ard to the use thereof as medic aments.

The enzyme WAFla is produced for example= through thrombin activatior from the thrombin-activwatable fibrinolysis inhibitor zymogen (TAF). The enzyme TAFI is also referred to as plasma procarboxypeptidase BB, procarboxypeptidase U o»r procarboxype ptidase R and is a proenzyme similar to carboxypeptidase= B (L.. Bajzar,

Arterioscler. T hromb. Vasc. Biol. 2000, pageas 2511 — 2518).

During formation of a clot, thrombin is generated as the final product of the coagulation cascade and Enduces conversion of soluble plasma fibrinogen to an insoluble fibrin matrix. At the same time, thrombin activates the endogenous fibrinolysis inhibitor TAF.

Activated TAI (TAFIa) is thus produced during thrombus formation and lysis from the zymogen TAF through the action of thromb in; thrombomodulin in a cormplex with thrombin incresases this effect about 1250-fold. TAFla cleaves basic am ino acids at the carboxy end of fibrin fragments. The loss of carboxy-terminal lysines ass binding sites for plasminogen then leads to inhibition of fibrirmolysis. Efficient inhibitors of TAFla prevent the loss of thease high-affinity lysine binding sites for plasminogen and, i n this way, assist endogenous fibrinolysis by plasmin: TAFla i nhibitors have profibrinolytic effects.

In order to mazintain hemostasis in the blood, mechanisms which lead to the clotting of blood and to the breaking up of clots have d eveloped; these are in equilibrium. If a disturbed equmilibrium favors coagulation, fib xin is produced in larger quantities, so that pathological forocesses of thrombus formation may lead to serious pathological states in humans.

Just like exces=ssive coagulation may lead to serious pathological states caused by thrombosis, aan antithrombotic treatment entails the risk of unwanted bleeding through disturbance oef the formation of a necessary hemostatic plug. Inhibition «f TAFla increases encdogenous fibrinolysis - without influencing coagulation and platelet aggregation - i.e. the disturbed equilibrium iss shifted in favor of fibrinolysis. It is thus possible both to counter the buildup of a clirically relevant thrombus, ard to increase the lysis of a pre—existing clot. On the other hana, buildup of a hemostatic p lug is not

® impaired, so that a hemorrhagic diathesis is probably rot to be expected (Bourmna et al.,

J. Thrombosis and Haemeostasis, 1, 2003, pages 1566 - 1574).

Inhibitors of TAFia have already been described in the international application s WOO03/013526 and WO033/061653.

The TAF la inhibitors of th € invention are suitable for a prophylactic and for a th erapeutic use in humans suffering fwom disorders associated witk thromboses, embolism s, hypercoagulability or fibrostic changes. They are suitabl e both for acute and for long-term 1.0 therapy.

The invention therefore realates to a compound of the formula

X

SE © z—0 u N

LS and/or all stereoisomeric Forms of the compound of the formula | and/or mixtures of these forms in any ratio, &and/or a physiologically tolera ted salt of the compound of the formula |, where

Uis 1) hydrogen atom, 2) -(C1-Cg)-ali=y, 3) -(C3-Cg)-cy cloalkyl, 4) fluorine, 5) -O-CF3 or 6) -CF3, »s5 Xis the radical of the formula Il -(A1)m-A2 {I} in which m is the integer zero ©r 1, .

Atis 1) -(CH=)x- in which n is the integer 1, 2 or 3, or 2) -O-(CH2)p- in which n is the integesr zero, 1, 2 or 3,

A2is 1) 4-to 15-membered Het ring in whi ch Het ring comprises a®t least one MN atom and is substituted by &an amino group and maw

® additionally be substituted ind ependently of one another orice, twice or three times by a -(C4-Cg3)-alkyl, halogen, -CF3 or -O-CIF3, 2) -(C4-Cg)-alkyl-NH»o or 3D -(C3-Cg)-cycloalkyl-NHa,

Yis 1) the radiczal of the formula ill

A3-(Ad)o-(AS)p (mn where a) A 3is -(C3-Cg)-cycloalky! or -(C2-Cg)-alkynylene, in which cycloal kyl or allkynylene is unsubstituted or substituted independently of one arother omce, twice or three times by -O-R10 or R1,

A 4 is -N(R2)2- in which R2 is as defined below, and the two R2 radicals ame defined independently of one ancther,

A 5is absent, ois the integer zero or 1, and

R_10 is a hydrogen, -(C4-Cg)-alkyl or -(Cg-C14)-aryl, b) A 3is -(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstituted or sLbstituted insdependently of one another once, twice or three times by -O-R1 0 or R1,

Ad is -N (R2)-, and

ASis ad1) -C(O)-R3, ad2) -C(O)-N(R4)-R5, ad3) -(SO2)-R6, or aD4) -C(O)-O-R7, : ois the imteger 1, and p is the imteger 1, c) Ais cyclic amine having 3 to 8 ring atoms in which cyclic amine &s ursubstituted or substituted independently of one another once, tice or tharee times by R1,

A4 and A\5 are as defined under b), where AS is bonded to the N atom of A3, o is the imnteger zero, and p is the imteger zero or 1, or d) AZZ is -(CH2)q-(Cg-C14)-aryl in which aryl is unsubstituted or substituted in dependently of one another once, twice or three times by R1,

A4 and M5 are as defined under b), o is the irteger zero or 1, and

® p is the integer 1, and gis the integer zero, 1, 2or 3, e) A3 is -{CHo)-Hest in which Het is a 4- to 15-m embered Het ring, and Het ring is unsubstituted or substituted independe ntly of one another oncze, twice or three tirmes by = O or R1,

A4 and A5 are as defin ed under b), o is the integer zero or 1, p is the integer 1 and ris the integer zero, 1, 2or 3, f) A3is +(CH2)g-(Cp-C14)-ary! in which aryl is umsubstituted or substitiated independently o f one another once, twice or three times by R1,

Ad is -O-,

AS is -(Cg-C44)-aryl in which aryl is unsubstituted or substituted independe=ntly of one another once, twice or three times by R1 0 and p are the integer- 1 and q is the integer zero, 1, 2 or 3, 9) -CH(-(Ce-C14)-aryl)-(Cg-C14)-aryl, where R1 is a) -(Cg-C14)-aryl, where aryl is unsubstituted or- substituted independe=ntly of one another once, twice or three times by -(C¢-Cg)-alkyl, -(Cg-C4)-axalkyl- (C3-Cg)-cycloal kyl, -CF3, =O, -O-CF3 or halegen, b) 4- to 15-membesred Het ring, c) -(C1-Cg)-alkyl, d) -(Co-C4)-alkyl-( C3-Cg)-cycloalkyl, e) -CF3, f) -O-CFj or a) halogen, where R2 is a) -(Cg-C14)-ary! 3n which aryl is unsubstituted =or substituted indepencdently of one another once, twice or three times by R1, b) -(C4-Cg)-alkyl i n which alkyl is unsubstituted or substituted indepen dently of one another once, twice or three times by R1,

® c) -(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstituted or substituted independently of one another once, twice or three times by R 1, d) -CF3 or e) hydrogen atom, 5 where R3, R6 and R7 are identical or different are independemtly of one another a) -(C4-Cg)-alkyl in which alkyl is unsubstituted or substitmuted independently of one another once, twice or three times by R1, b) -(Cg-C14)-aryl in which aryl is unsubstituted or substitLited independently of one another once, twice or three times by R1, c) 4- to 15-membered Het ring in which Het ring is unsubstituted or substituted independently of one another once, twice or three times by R1, d) -(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstituted or substituted independently of one another once, twice or three times by R71, or e) hydrogen atom, 1= where R4 and RS are identical or different are independently of one another a) -(C4-Cg)-alkyl or =(C,-Cyp)-alkenyl, in which alkyl! or alkeenyl is unsubstituted or substituted independently of one another once, twice or three times by R1, b) -(Cg-C14)-aryl in which aryl is unsubstituted or substitu ted independently of one another once, twice or three times by R1, c) 4- to 15-membered Het ring in which Het ring is unsubstituted or substituted independently of one another once, twice or three times by R1, d) -(C3-Cg)-cycloalky! in which cycloalkyl is unsubstituted or substituted independently of one another once, twice or three timess by R1, or 2s e) hydrogen atom, or

R4 and RS form together with the nitrogen atom to which they are bonded a ring having 3 to 8 ring atoms which may, in addition to the nitrogen atom, also comprise one to two additional heteroatoms from t#he series oxygen, sulfur or nitrogen, 30s Yis 2)the radical of the formula IV, 0] N R8 1-5 where R8 is

® a) -(C + -Cg)-alkyl in which alkyl is unstbstituted or substitute=d inde=pendently of one another once, twice or three times by R1, b) -(Ce5-C14)-aryl in which ary! is unsubstituted or substitute=d indespendently of one another once , twice or three times Tby R1, c) 4- tao 15-membered Het ring in which Het ring is unsubstituted or submstituted independently of one arother once, twice or three times by R1, d) -(C-3-Cg)-cycloalky! in which cycloalkyl is unsubstituted or substituted independently of one a nother once, twice or three times by R1, or e) hydrogen atom,

Yis 3) the radical of the formula V oO

R15 R17 WR ba fg | v) 2 fo R13

R18 R18 where in case a)

R12is 1) -(C 1-Cg)-alkyl in which alkyl is uns ubstituted or substitut.ed independently of one another once, twice or three times by R1, 2) -(C o-C3)-alkyl-(C3-Cg)-cycloalkyl iwn which cycloalkyl is unsubstitumted or substituted independenti=y of one another once-, twice or three time=s by R1, 3) -(Cg-C3)-alkyl-(Cg-C14)-aryl in which aryl is unsubstituted or substitutead independently of one another once, twice or three ti mes by R1, or 4) -(C&-C3)-alkyl-Het in which Het is wunsubstituted or substituted ind ependently of one another once, twice or three times by R1, and

R13is 1) -(C-Ca)-alkyl-(Cg-C14)-ary! in wh ich alkyl and aryl are e=ach unsubstituited or substituted independent] y of one another once, twice or three time2s by R1, or 2) -(C-Cjy)-alkyl-Het in which alkyl and Het are each unsubstituted or substitute d independently of one another once, twice or three ti mes by R1, where in case b)

R12is1) hydrogen atom,

® 2) -(C1-Cg)-alkyl in which alkyl is wunsubstituted or substituted independently of one another once, tw~ice or three times by R1, 3) -(Cp-C3)-alkyl-(Cg-C14)-aryl in which aryl is unsubstituted cr sub stituted independently of one another once, twice or three time=s by R1, or 4) -(Cp-C3)-alkyl-Het in which Het: is unsubstituted or substitufted indeependently of one another once, twice or three times by R1, an d

R13 is -CH(R8)-R9 where R8 and R9 are indespendently of one another -(Ces-C14)-aryl or Het in which Het and aryl are each unsubstituted or sub stituted independently of one another once, twice or three time=s by -O-€C1-C4)-alkyl or R1 and

R16, R17, R18 and R19 are identical or differ-ent and are independently of one another 1) hydrogen atom, 2) -(C1-Cg)-alkyl, in which alkyl is unsubstituted or substituted once or twice by R1, 3) halogen, 4) -OH, 5) -NH2, 6) -(Cp-C3)-alkyl-(Cg-C14)-aryl in which alkyl and aryl are each unsubstituted or substituted ind ependently of one another once, twice or three times by R1, or 7) -(Cg-C3)-alkyl-Het in which alkyl and Het are each unsubstituted or substituted independently of on e another once, twice or three times by R1, or

R16 and R 17 or R18 and R19 form together with the carbon atom to which they are respectively bonded a ring having 3 to 6 ring atoms, or

Yis 4) the radical of the formula Vi,

R27 Na R24 — oa ‘ros (VI) os Reo

® wher~e

R24 and R25 are identical or differ ent and are independently «of one another 1) hydrogen atom, 2) -(C4-Cg)-alkyl in which alkyl! is unsubstituted or substituted once or twice by R1, 3) -(Cp-C3)-alkyl-(Cg-C=14)-ary! in which alkyl and aryl are each unsubstituted or substituted independently of ore another once, twice or three times by R1, 4) -(Cp-C3)-alkyl-Het in which alkyl and Het are eaach unsubstituted or substituted independ ently of one another once, twice or three times by R1, or 5) -(Cp-C3)-alkyl-(C3-C g)-cycloalkyl, or

R24 and R25 form together with th e nitrogen atom to which they are bonded a ring Bhaving 3 to 8 ring atoms whichs may, in addition to the nitrogen atom, also comprise one to two additional hetesroatoms from the series oxygen, sulfur or nitroggen,

R26, R27, R28 and R29 are identical or different and are inde=pendently of one anotker 1) hydrogen atom, 2) -(C1-Cg)-alkyl in which alkyl is unsubstituted or substituted once or twice by R1, 3) halogen, 4) -OH, 5) -NHo, 6) -(Cg-C3)-alkyl-(Cg-C 44)-aryl in which alkyl and aryl are each unsubstituted or subsstituted independently of ore another once, twice or three times toy R1, or 7) -(Cp-Cgy)-alkyl-Het in which alkyl and Het are ea ch unsubstituted or substituted independently of one another once, twice or three times by R1, or

R26 and R2 7 or R28 and R29 form togeth er with the carbon atom to which they are respectively bonded a ring having 3 to 6 rieng atoms,

Zis 1) hydrogen atom, 2) -(C1-Ceg)-alkyl,

® 3) (C1-Cg)-alkyl-OH, 4) -(Cg-C4)-alkyl-(C3-Cg)-cycloalkyX, 5) -(C1-C1g)-alkyl-O-C(0O)-O-R1, 6) -(CH2)~(Cg-C14)-aryl in which a ryl is unsubstituted or substitu ted independently of one another on ce, twice or three times by R1 , and ris the integer zero, 1, 2 or 3, or 7) -(CHo)g-Het in which Het is unsubstituted or substituted indepesndently of one another once, twice or three times by R1, and s is the inte ger zero, 1, 2o0r3.

The invention further relates to the compound of the formula la

X fo) SA) N= (ja) z—0 YU NT where

Uis 1) hydrogen atom, 2) -(C1-Cg)-alkyl, 3) -(C3-Cg)-cycloalkyl, 4) fluorine, 5) -O-CF3 or 6) -CF3,

Xis thes radical of the formula Il in which m is the integer zero or 1,

A1 is 1) -(CH2)pn- in which nis the integer 1, 2 or 3, or 2) -O-(CH2)p- in which n is the integer zero, 1, 2 or 3,

AZ is 1) 4- to 15-membered Het ri ng in which Het ring is selected from the group of acridinyl, azepinyl, azetidinyl, aziridinyl, benzimidazal inyl, benzimidazolyl, carbolinyl, quina. zolinyl, quinolinyl, 4H-quinolizEnyl, quinoxalinyl, quinuclidinyl, chronmanyl, chromenyl, cinnolinyl, deeca- hydroquinolinyl, imidazolidinyl, irmidazolinyl, imidazolyl, 1H-inda&zolyl, indolinyl, indolizinyl, indolyl, 3H-i ndolyl, isobenzofuranyl, isochr-omanyl, isoindazolyl, isoindolinyl, isoindo lyl, isoquinolinyl (benzimidazo yl), isothiazolidinyl, 2-isothiazolinyl, i sothiazolyl, isoxazolyl, isoxazcolidinyl, 2- isoxazolinyl, morpholinyl, naphtheyridinyl, octahydroisoquinolinywl,

® osxadiazolyl, 1,2,3-oxadiazolyl, 1, 2 4-oxadiazolyl, 1,2,5-oxa diazolyl, 1 ,3,4-oxadiazolyl, oxazolidinyl, o xazolyl, pyrimidinyl, phenaanthridinyl, pshenanthrolinyl, phenazinyl, phe nothiazinyl, phenoxathiiny~l, phenoxazinyl, pshthalazinyl, piperazinyl, piperidi nyl, pteridinyl, puryny!, pymranyl, pyrazinyl, pyroazolidinyl, pyrazolinyl, pyraz olyl, pyridazinyl, pryidoox&azolyl, pyridoimidazolyl, pyridothiazolyl, pyridothiophenyl, pyridiny=l, pyridyl,

Pyrimidinyl, pyrrolidinyl, pyrroliny=!, 2H-pyrrolyl, pyrrolyl, teetrahydroisoquinolinyl, tetrahydmroquinolinyl, tetrahydropyr idinyl, 6H-1,2,5- thhiadazinyl, 1,2,4-thiadiazolyl, 1, 2 5-thiadiazolyl, 1,3,4-thia=diazolyl, tlhianthrenyl, thiazolyl, thienothia zolyl, thienooxazolyl, thiernoimidazolyl, t hiomorpholinyl, triazinyl, 1,2,3-tmriazolyl, 1,2,4-triazolyl, 1,22,5-triazolyl, 4 .3,4-triazolyl and xanthenyl and in which the Het ring is substituted by an amino group and may additionallly be substituted indepencdently of one another once, twice or three timees by a -(C1-C3)-alkyl, halogen, -CF3 or —

O-CF3, 2) -(C41-Cg)-alkyl-NH2 or 3) -(C3-Cg)-cycloalkyl-NH2,

Y is M)the radical of the formula lll wshere 2) A3 is -(C3-Cg)-cycloalkyl or -(C2-Cg)-alkynylene in which cycloalkyl or alkylnylene is unsubsti tuted or substituted indepe=endently of one another once, twice or three times by R1,

Ad is —-N(R2)o- in which FR2 is as defined below, arad the two R2 radicals are defined indegoendently of one another,

AS5 is absent and ois the integer zero or 1, bo) A3 is -(C3-Cg)-cycloalkyl in which cycloalkyl is uns ubstituted or substituted independently of one another once, twi ce or three times by R1,

Ad is—N(R2)-, and

A5is a)1) -C(O)-RS3, a)2) -C(O)-N(R=4)-RS5, a)3) -{SO2)-R6. or a)d) -C(0O)-O-R77, ois the integer 1, and

® p is the integer 1, c) A3 is cyclic amine from the group of propylamine, azetidine, pyrrolidine, piperidine, azepanes or azocanes, in which cyclic am ine is unsubstituted or substitu ted independently of one another once2, twice or three times by R1,

Ad and A5 are as defined under b), where AS is bonded to the N atom of A3, o is the integer zero, and : p is the integer zero or 1, or d) A3 is -(CH2)q-(Cg-C14)-arylin which aryl is selected from the grosup of phenyl, naphthyl, anthryl or fluoreny! and is unsubstituted or substituted independently of one another once, twice or three time=s by R1,

A4 and AS are as defined under b) o is the integer zero or 1, and p is the integer 1, and q is the integer zero, 1, 2 or 3, e) A3 is -(CH2)-Het in which Het is as defined above and is unsubstituted or substituted independently of one another once, twice or three times by =O or R1,

A4 and AS are as defined under b), ois the integer zero or 1, p is the integer 1 and ris the integer zero, 1, 2 or 3, f) A3 is -(CH2)q-(Cg-C14)-aryl in which is aryl is unsubstituted or substituted independently of one another once, twice or three times by R1,

Ad is -O-,

AS5 is -(Cg-C14)-aryl in which aryl is unsubstituted or substituted independently of one another once, twice or three times by R1, o and p are the integer 1 and q is the integer zero, 1, 2 or 3, g) -CH(phenyl)-phenyl, where R1 is

- ® a) -(Cg-C14)-aryl in which aryl is as defined above and in which aryl is unsubstituted or iss substituted independently of one another once, twice or three timeas by -(C4-Cg)-alkyl, -(Co-C=)-alkyl-(C3-Cs)- cycloalkyl, -CF3, =O, -O—CF3 or halogen b) 4- to 15-membered Het ring in which Het is amas defined above, c) -(C1-Cg)-alkyl, d) -(C3-Cg)-cycloalk vl, e) -CF3, f) -O-CF3 or g) halogen, wwhere R2 is a) -(Cg-C14)-ary! in which aryl is as defined above and is unsubstituted or saubstituted independently of one another once, twice or thre=e times by R1, b) -(C1-Cg)-alkyl in wohich alkyl is unsubstituted cr substituted oo independently of o»ne another once, twice or three times by

R1,

C) -(C3-Cg)-cycloalky~l in which cycloalkyl! is unsumbstituted or substituted independently of one another once, twice or three times by R1, d) -CF3 or e) hydrogen atom, where R3, R6 and R7 are identic al or different are independ ently of one armother a) -(C4-Cg)-alkyl in which alkyl is unsubstituted o r substituted independently of ore another once, twice or th-ree times by

R1, b) -(Cg-C14)-aryl in which aryl is as defined abov e and is unsubstituted or su bstituted independently of cone another once, twice or three times by R1,

® c) 4- to 15-membered Het ri ng in which Het ring is ass defined above and is unsubstitute=d or substituted indepenedently of one another once, twice or three times by R1, d) -(C3-Cg)-cycloalky! in whi ch cycloalkyl is unsubstit-uted or 3 substituted independently of one another once, twice or three times by R1, or <) hydrogen atom, where R4 and R5 are identical or differeent are independently of one another a) -(C1-Cg)-alky! or -(C2-C1o)-alkenyl, in which alkyl o r alkenyl is unsubstituted or substitutesd independently of one another once, twice or three timess by R1, bo) -(Cg-C14)-aryl in which aryl is as defined above amd is unsubstituted or substitutead independently of one another once, twice or three times by R1, cc) 4- to 15-membered Het rirg in which Het ring is as- defined above and is unsubstitute«d or substituted independently of one another once, twice o rthree times by R1, dq) -(C3-Cg)-cycloalky! in whiesh cycloalkyl is unsubstituted or substituted independently of one another once, twiece or three times by R1, or e) hydrogen atom, or

R4 and RS form together with the nitrogeen atom to which they aree bonded a ring having 3 to 8 ring atoms selected from the group of propylamine, azetidin e, pyrrolidine, piperidine, azeparaes, azocanes, azepine, cdioxazole, dioxazire, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazo le, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazedline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ketopipearazine, morpholine, [1,4]oxazep ane, oxazole, piperazine, pyrazine, pyrazolez, pyrazoline, pyrazolidine, pyridaazine, pyridine, pyrimidinez, pyrrole, pyrrolidimone, pyrroline, tetrahydropyridire, thiazole, thiadiazole, thiazolid ine, thiazoline, thiomorpholine, 1 ,2,3-triazine, 1,2,4-triazirme, 1,3,5- triazine, 1,2,3-triazole or 1,2,4-triazole,

® Yis 2)the radical of the formula IV where formula IV is & compound from the group of azetidin-2-one, py~rrolidin-2-one, piperidin-2-one, azepan-2-one and azocan-2-0 ne and is substituted on the nitrogen atom in each casex by R8, where R8 is a) -(Cq-Cg)-alkyl in which alkyl is unsubs tituted or substituted independeritly of one another once, twice or t hree times by R1, b) -(Cs-C14)-aryl in which aryl is as defin ed above and is unsubstitut ed or substituted independently of one another once, twice or three timess by R1, c) 4- to 15-membered Het ring in which Het ring is as defined above and is unsubstituted or substituted independe ntly of one another once, twice or thr-ee times by R1, d) -(Cg3 -Cg)-cycloalkyl in which cycloalkyl is unsubstituted or subsstituted independently of one anothwer once, twice or three times by R21, or e) hydr-ogen atom,

Yis 3)the radical of the formula V, where in case a)

R12 is 1) -(C4-Cg)-alkyl in which alkyl is Linsubstituted or substituted independently of one another orice, twice or three times by=

R1, 2) -(Cp-C3)-alkyl-(C3-Cg)-cycloalkyy! in which cycloalkyl is unsubstituted or substituted indeependently of one another once, twice or three times by R1 3) -(Cg-C3)-alkyl-(Cg-C14)-ary! in vwhich aryl is as defined above and is unsubstituted or su bstituted independently of one another once, twice or three times by R1, or 4) -(Co-C3)-alkyl-Het in which Het i=s as defined above and is unsubstituted or substituted inde pendently of one another once, twice or three times by R1,, and

R13 is 1) -(Cp-C3)-alkyl-(Cg-C14)-aryl in wrhich alkyl and aryl is as defined above and are each unsubstituted or substituted independently of one another once, twice or three times by

R1, or 2) -(Cg-C3)-alkyl-Het, in which alkyl and Het is as defined above and are each unsubstituted or substituted

® inde2pendently of one another once, twice or three times by

R1, or in case b)

R12is 1) hydr-ogen atom, 2) (C1 -Cg)-alky! in which alkyl is ursubstituted or substituted inde=pendently of one another twice or three times by

R1, 3) -(Cow-C3)-alkyl-(Cg-C14)-ary! in which aryl is unsubstituted or subsstituted independently of one &nother once, twice or threes times by R1, or 4) -(Co -C3)-alkyl-Het in which Het is unsubstituted or subsstituted independently of one &another once, twice or three times by R1, and

R13 is -CH(R8)-RS where R8 and R9 are indepesndently of one another - (Cg-C14)-amyl or Het in which Het and arwyl are each as defined above and are unsubstituted or substituteed independently of one another once, twice or three times by -O—(C4-C4)-alkyl or R1, and

R16, R17, R18 and R19 are identical or different and axe independently of one another 1) hydrogen atom, 2) -(C1-Cg)-all=yl in which alkyl is unsubstitu ted or substituted once or- twice by R1 3) halogen, 4) -OH, 5) -NHo, 6) -(Cp-C3)-alkyl-(Cg-C14)-aryl in which alkyl and aryl is as defined above and aare each unsubstituted or subsstituted independently of one another once, twice or three times by R1, or 7) -(Cp-C3)-alkcyl-Het in which alkyl and Het 3s as defined above and are each unssubstituted or substituted indeependently of one another- once, twice or three times by R1, or

R16 and R17 or R18 and R19 form together with the cambon atom to which they are respectively borded a ring having 3 to 6 ring atoms from the group of cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, or

® Yis 4)the radical of the formula VI, where

R24 and R25 are identical or different and are irmdependently of one anoth «er 1) hydrogen atom, 2) -(C1-Cg)-alkyl in which alkyl is unsubstituted or substituted cance or twice by R1, 3) -(Co-C3)-alkyl-(Cg-C14)-aryl in whrich alkyl and aryl is as def ined above and are each unsubstituted or substituted independertly of one another once, twice or three ti mes by R1, 4) -(Cp-C3)-alkyl-Het, in which alkyl and Het is as defined above and are each unsubstituted or substitut-ed independently of one amnother once, twice or three times by R1, cor 5) -(Cp-Cg)-alkyl-(C3-Cg)-cycloalkyl, or

R24 and R25 form together with the nitrogen ato m to which they are bonded a ring having 3 to 8 ring atoms from the group of p ropylamine, azetidine, pyrrolidine, piperidine, azepanes, azocanes, azepine, dioxazole, dioxazine, 1,4- diazepane, 1, 2-diazepine, 1,3-diazepine, 1,4-dia=epine, imidazole, imidazo line, imidazolidine, isothiazole, isothiazolidine, isothia=oline, isoxazole, isoxazolime, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine, [1,4Joxazepane, oxazole, piper-azine, pyrazine, pyrazole, pyrazolime, pyrazolidine, pyridazine2, pyridine, pyrimidine, pyrrole, pyrrolidinone, pyrrolF ne, tetrahydropyridine, thiazole, thiadiazole, th iazolidine, thiazoline, thiomorpholin=e, 1,2 3-triazine, 1,2,4-tria=zine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole,

R26, R27, R28 and R29 are identical or different ~and are independently of cone another 1) Fydrogen atom, 2) —(C1-Cg)-akyl in which alkyl is unsumbstituted or substituted orace or twice by R1, 3) halogen, 4) ~OH, 5) -NH», 6) - (Co-C3)-alkyl-(Cg-C14)-aryl in whic=h alkyl and aryl is as defined above and are each unsubstituted o r substituted independent! y of one another once, twice or three tim es by R1, or

® 7) -(Cp-C3)-alkyl-Het in which alkyl and Het is as defined above and are each unsubstit uted or substituted independerutly of one another once, twice or thre e times by R1, or

R26 and R27 or R28 and R29 form togesther with the carbon atom to wwrhich they are respectiv ely bonded a ring having 3 to 6 ring atoms from the group of ccyclopropyt, cyclobuty=|, cyclopentyl or cyclohexyl,

Zis 1) hydrogen atom, 2) -(C1-Cg)-alkyl, 3) (C3-Cg)-cycloalkyl, 4) (C1-C10)-alkyl-O-C(O)-O -R1, 5) -(CH2)~(Cg-C14)-aryl in which aryl is as defined above and is unsubstituted or substitut ed independently of one anothesr once, twice or three times by R1, and r i s the integer zero, 1, 2 or 3, or 6) -(CH»p)s-Het in which Het is as defined above and is uns=ubstituted or substituted independently of one another once, twice or three times by R1, and s is the integer zero, 1, 2 or 3.

The invemntion further relates to the comapound of the formula la where

Uis hydrogen atom, -CF3, fluorine or -CHg,

X is the radical of the formula Il in which m is the integer 1,

A-lis 1) -(CH2)-, 2) -O-(CH2)p- in which nis the integer zero or 1, or 3) covalent bond,

A22is 1) aminopyridyl in which aminopyridyl is unsubstitutesd or substituted independently of one another once, twice or three times by -(Cq-

Cg)-alkyl, halogen or -CH3, 2) aminothiazolyl in wvhich aminothiazolyl is unsubst ituted or substituted indepe=ndently of one another once, twice or three times by -(C1-Cg)-alkyl, halogen or —CH3, 3) -(C4- Cg)-alkyl-NH2 or 4) -(C3-Cg)-cycloalky/I-NHo,

Yis 1) the radical of the formula lll wshere

_ a) A3 is -(C3-Cg)-cycloalkyi or (C9-Cg)-alkynylene in which c=ycloalkyl of alkynylene is unsubstituted or substituted independently of one another once, twice or three tirmes by -O-R10 or R1,

Ad is —-N(R2)5- in which R2 is as defined below, and the two R2 radicals are defined independently of one another,

AS is absent, o is the integer z ero or 1, and

R10 is hydrogen, -(C1-Cg)-alky! or phenyl, b) A3 is -(C3-Cg)-cycloalkyl in wh ich cycloalkyl is unsubstituted or substituted independently of ore another once, twice or three times by -O-R10 or R1,

A4 is-N(R2)- , and

AS5is a)1) -C(O)-R3, a)2) -C(O)-N(R4)-R5, a)3) -(S02)-R6, or ay) -C(O)-O-R7, o is the integer 1, and p is the integer 1,

Cc) A3 is cyclic amine having 3 to 8 ring atoms in which cyclic zmmine is unsubstituted or substituted independently of one another o nce, twice or three times by R1,

A4 and A5 are as defined under b), where R5 is bonded to the N atom of A3, o is the integer zero, and p is the integer zero or 1, or d) Adis «(CH2)q-(Ce-C14)-ary! in wshich aryl is unsubstituted or substituted independently of one» another once, twice or threee times by R1,

A4 and AS are as defined under b), o is the integer zero or 1, and p is the integer 1, and q is the integer zero, 1, 2 or 3, e) ~A3 is -(CHp)r-Het in which Het is pyrrolidine, benzothiophene= or

FRiperidine, which is unsubstituted or substituted independent! y of one another once, twice or three times by =O or R1, 15 #24 and AS are as defined under b),

® 0 is the integer zero or 1, p is the integer 1 and ris the integer zero, 1, 2 or 3, f) A3 is -(CH2)q-phenyl in which phenyl is unsubstituteed or substituted independently of one another once, twice or three tirmes by R1,

A4 is -O-,

A5 is phenyl, in which phenyl &s unsubstituted or sub stituted independently of one another once, twice or three tirmes by R1, 0 and p are the integer 1 and p is the integer 1 or 2, where= R1 is a) phenyl, where phenyl iss unsubstituted or subsstituted independently of one another once, twice of three tirmes by -(C1-Ca)-alkyl, b) triazolyl or pyridinyl, c) -(C1-Cy)-alkkyl, d) -(C3- Cg)-cycloalkyl, e) -CF3, f) -O-CF3, a) fluorine or h) chlorine, where R2 is a) phenyl in which pheny lis unsubstituted or su bstituted independently of once, twice or —three times by

R1, b) -(Cq- Cg)-alkyl in whic=h alkyl is unsubstituted or substituted independently of one another once, twice or three times by

R1, c) -(C3-Cg)-cycloalkyl in which cycloalkyl! is unssubstituted or substituted independently of one another once, twice or three times by R1, d) -CFg3 or e) hydrogen atom,

® where R3, R6 and R7 are identical or different are independently of one another a) -(C4-Cg)-alkyl in which alkyl! is unsubstituted om substituted independently of one another once, twice or th ree times by

R1, b) -(Cg-C14)-aryl in which aryl is unsubstituted or substituted independently of one another once, twice or th ree times by

R1, c) 4- to 15-membered Het ring in which Het ring i=s unsubstituted or substituted independently of cane another once, twice or three times by R1, d) -(C3-Cg)-cycloalk yl in which cycloalkyl is unsutostituted or substituted independently of one another once , twice or three times by R1 , or e) hydrogen atom, where R4 and R5 are identical or different are independently of one another a) -(C1-Cg)-alkyl or —(C,-Cg)-alkenyl, in which alkyl or alkenyl is unsubstituted or substituted independently of o=ne another once, twice or three times by R1, b) -(Cg-C14)-aryl in which aryl is unsubstituted or substituted independently of one another once, twice or three times by

R1, c) 4- to 15-membered Het ring in which Het ring iss unsubstituted or substituted independently of 0 ne another once, twice or three times by R1, d) -(C3-Cg)-cycloalky! in which cycloalkyl! is unsutostituted or substituted independently of one another once, twice or three times by R1 , or e) hydrogen atom, or

R4 and RS form together with the nitrogen atom to which they are bconded a ring derived from azetidine, pyrrolidine, piperidine, azepanes, azocanes, azepine, dioxazole, dioxazine, 1,4-diazepane, 1, 2-diazepine, 1,3-diazepine, 1 ,4-diazepine, imiciazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, iso thiazoiine, isoxazole, isoxazoline, isoxazolidine, 2~isoxazoline, ketopiperazine, rnorpholine,

® 21 [1,4Joxazepane, oxazole, piperazine, pyrazine, pyrazole, pyraz=aline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidinone, pyrrolinee, tetrahydropyridine, thiazole, thiadiazole, thiazolidine, thiazoline2, thiomorpholine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2 4-triazole, 5s Yis 2) the radical of the formula IV selected from the group of azettidin-2-one, pyrrolidin-2-one or piperidin-2-one, where the radical is substit uted on the nitrogen atom in each case by R8, where R8 is a) -(C1-Cg)-alky! in which alkyl is unsubstituted or =substituted independently of one another once, twice or threze times by R1, b) phenyl in which phenyl is unsubstituted or subst ituted independently of one another once, twice or three times by R1 , c) hydrogen atom or d) -(C3-Cg)-cycloalkyl ire which cycloalkyl is unsubstituted or substituted independently of one another once, twice or three times by R1,

Yis 3) the radical of the formula V where in the case a)

R12 is 1) -(C1-Cg)-alkyl in which alkyl is unsubstit__ited or substituted independently of one another once, twice or threee times by R1, 2) -(Co-C3)-alkyl-(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstituted or subsstituted independently of ore another once, twice or three times by R1, or 3) -(Cg-Cg)-alkyl -phenyl in which phenyl is unsubstituted or substituted independ ently of one another once, twice or three times by R1, and

R13 is 1) -(Co-C3)-alkyl-pheny! in which alkyl and phenyl are each unsubstituted or substituted independently of one another once, twice or three times by R1, or 2) -(Co-Cg3)-alkyl-pyridyl in which alkyl and pyridyl are each unsubstituted or substituted independently of one another once, twice or three times by R1, or in the case b)

R12 is 1) hydrogen atorm, 2) -(C1-Cg)-alky1 in which alkyl is unsubstit uted or substituted independently of once, twice or three times by R1,

® 3) -(Cg-C3)-alkyl-phenyl in which phenyl is uansubstituted or substituted indepemdently of one another once, t wice or three times by R1, or 4) -(Co-C3)-alkyl-pyridyl in which alkyl and peyridy! are each unsubstituted or substituted independently of on e another once, twice or three time sby R1, and

R13 is -CH(R8)-R9 wherea R8 and R9 are independentlwy of one another phenyl or pyridyl ire which phenyl! or pyridyl are e ach unsubstituted or substituted inde pendently of one another oncee, twice or three times by -O-(C1-C 4)-alkyl or R1, and

R16, R17, R18 and R19 are idertical or different and are independently of one another 1) hydrogen atom, 2) -(C4-C3)-alkyl in which alkyl is unsubstituted or =substituted once or twice by R1, 3) fluorine, 4) -OH, 5) -NH»2 or 6) -(Co-C3)-alkyl-pheenyl, in which alkyl and phenyl are each unsubstituted or s ubstituted independently of ore another once, twice or three times by R1, or

Yis 4) the radical of the formula VI, where

R24 and R25 are identical or dif ferent and are independently «of one another 1) hydrogen atom, 2) -(C4-Cg)-alkyl in wvhich alkyl! is unsubstituted or substituted once or twice by R1, 3) -(Cp-Ca)-alkyl-phenyl in which alkyl and phenyl are each unsubstituted or substituted independently of ore another once, twice or three times by R1, or 4) -(Co-C3)-alkyl-(C3—Cs)-cycloalkyl, or

R26, R27, R28 and R29 are ide ntical or different and are independently of one another 1) hydrogen atom,

® 2) -(C1- Ca)-alk<yl in which alkyl is unsubsstituted or substituted once or twice by R1, 3) fluorine, 4) -OH, 5) -NH2 or 6) ~(Cp-C3)-alk-yl-phenyl in which alkyl an d phenyl are each unsubstituted or substituted independently of one another once, twice or threee times by R1, and

Z is hydrogen atom or (C1-C4)-alw/l.

The invention further relates to thee compound of the formulaa la, where

Uis hydrogen atom,

Xis the radical of the formula | 3 in which m is the integer 1,

A1lis -(CH2)-,

A2is aminopyridyl in whicch aminopyridyl is unsubstituted or substituted independently of orme another once, twice or three times by halogen or -CHg,

Yis 1) the radical of the formula lll where a) A3 is -(C3-Cg)-cycloalkyl in which cycloalkyl iss unsubstituted or substituted independently of one another once, twice or three tirmes by R1, and A4 and AS are absent, b) A3 is -(C3-Cg)-alkyrylene in which alkynylene= is unsubstituted or substituted independently ef one another once, twicez or three times by R1, and

A4 and AS are absent,

Cc) A3 is cyclic amine Maving 3 to 8 ring atoms in which cyclic amine is unsubstituted or substitute-d independently of one an other once, twice or three times by R1, and A4 and Aa5 are absent, d) A3 is -(CH2)g-phen-ylin which phenyl is unsulostituted or substituted independently of one another once, twice or three tires by R1,

Ad is -N(R2)- in which R2 i s as defined below

Asis a)l) -C(O)-R3, a)2) -C(O)-N(R4)—R5, a)3) -(S0O2)-R6 or

Claims (10)

® 70 Clai ms

1. A compound of the formula X So u = z—0 and/or all stereoisomeric forrns of the compound of the formula | and/or mixtures of these forms in any ratio, and/or a physiologically tolerated salt of the compound of the formula I, where Uis 1) hydrogen atom , 2) -(C4-Cg)-alkyl, 3) -(C3-Cg)-cycloalkyl, 4) fluorine, 5) -O-CF3 or 6) -CF3, Xis the radical of the form ula ll -(A1)m-A2 (in in which m is the integer zero or 1, Atlis 1) -(CH)n- in which n istheinteger 1,2 or 3, or 2) -O-(CH2)n- in wvhich n is the integer zero, 1, 2 or 3, A2is 1) 4- to 15-memb ered Het ring in which Het ring ccomprises at least one N atom and is substituted by an amino group and may additionally be substituted independently of onee another once, twice or three times by a -(C1-C3)-alkyl, halogen, -C F3 or -O-CF3, 2) -(C1-Cg)-alkyl-INH» or 3) -(C3-Cg)-cycloalkyl-NHo, Y is 1) the radical of the form ula Ill A3-(Ad)o-(Ad)p (nn where a) A3 is -(C3-Cg)- cycloalkyl or -(C2-Cg)-alkynylerae, in which cycloalkyl or alkynylene is unsubstituted or substituted incdependently of one

® another once, twice or three times by -O-R10 or R11, Ad is -N(R2)2- in which R2 is as defined below, ard the two R2 radicals are defined independently of one another, Ab is absent, ois the in teger zero or 1, and R10 is a hydrogen atom , -(C4-Cg)-alky! or -(Cg-C1 4)-aryl,

b) A3 is -(C3-Cg)-cycloalkyl in which cycloalkyl is uns ubstituted or substituted independent ly of one another once, twi ce or three times by -O-R10 or R1,

A4 is-N(R2)-, and AS5is a)l) -C(O)-R3, a)2) -C(O)-N(RR4)-RS5, a)3d) -(SO2)-R6, or a4) -C(0O)-O-Ri7, ois the integer 1, and p is the integer 1,

c) AJ is cyclic amine havin g 3 to 8 ring atoms in which cyclic amine is unsubstituted or substitLated independently of one eanother once, twice or three times by Rt,

A4 and AS are as define=d under b),

where AS is bonded to tke N atom of A3, o is the integer zero, and p is the integer zero or 1 , or d) A3 is -(CH2)q-(Ce-C14)—aryl in which aryl is unsubsstituted or substituted independentBy of one another once, twicze or three times by R1,

A4 and A5 are as define d under b), o is the integer zero or 1 , and p is the integer 1, and q is the integer zero, 1, 2 or 3,

e) A3 is -(CH2)-Het in which Het is a 4- to 15-membesred Het ring, and Het ring is unsubstituted or substituted indeperdently of one another once, twice or tharee times by =O or R1,

A4 and AS are as define«d under b), ois the integer zero or 1 , p is the integer 1 and

® ri sthe integer zero, 1, 2 or 3,

f) AJ is -(CH2)q-(Ce-C14)-aryl, in which aryl is unsubstituted or substituted independently of one anaether once, twice or three tines by R1,

A4 is -O-, AS is -(Cg-C14)-aryl, in which aryl is munsubstituted or substituted independently of one another once, twice or three times by R1, o and p are the integer 1 and q i s the integer zero, 1, 2 or 3, a) -GH(-(Ce-C14)-aryl)-(Ce-C14)-aryl, where R1 is a) -(Ce-C14)-aryl, where aryl is u nsubstituted or substituted independently of one another nce, twice or three times b=y -(C1-Ce)-alkyl, -(Cp-C4)-alkyl-CC3-Cg)-cycloalkyl, -CF3, =O, -O-CF 3 or halogen, b) 4- to 15-membered Het ring, c) -(C1-Cg)-alkyl, d) -(Cp-Cq)-alkyl-(C3-Cg)-cycloal kyl, e) -CF3, f) -O-CFz or a) halogen, where R2 is a) ~(Cg-C14)-aryl in which aryl is wnsubstituted or substituted independently of one another once, twice or three times bwy R1, b) -(C1-Cg)-alky! in which alkyl is unsubstituted or substitutecd independently of one another osnce, twice or three times byy R1, Cc) -(C3-Cg)-cycloalkyl in which cyesloalkyl is unsubstituted or substituted independently of on e another once, twice or three times by R1, d) -CF3 or e) hydrogen atom,

® © j006 07088 where R3, R6 and R7 are id entical or different is indeperdently of one another a) -(C1-Cg)-alky! in which alkyl is unsubstitute=d or substituted independently of one another once, twice cor three times by

R1,

b) -(Cg-C14)-aryl in which aryl is unsubstitute=d or substituted independently of one another once, twice cor three times by R1,

c) 4- to 15-membered Het ring in which Het ring is unsubstituted or substituted independently= of one another once, twice or three times by R1,

d) -(C3-Cg)-cycloalky! in which cycloalkyl is u nsubstituted or substituted independently of one another once, twice or three times by R1, or e) hydrogen atom, where R4 and R5 are identical or different is independermtly of one another a) -(C1-Cg)-alkyl or -(C,-Cqo)-alkenyl, in which alkyl or alkenyl is unsubstituted or substituted independently of one another once, twice or three times by R1,

b) -(Cg-C14)-aryl in which aryl is unsubstitute=d or substituted independently of one another once, twice or three times by R1,

c) 4- to 15-membered Het ring in which Het riling is unsubstituted or substituted independently of one another once, twice or three times by R1,

d) -(C3-Cg)-cyclo alkyl in which cycloalkyl is umnsubstituted or substituted ind ependently of one another osnce, twice or three times by R1, or e) hydrogen atom, or

R4 and RS form together with the nitrogen atom to whicha they are bonded a ring having 3 to 8 ring atoms which may, in addition to —the nitrogen atom, also comprise one to two additional heteroatoms from the= series oxygen, sulfur or nitrogen,

Y is 2) the radical of the formula IV,

® 74

0] ah , (IV) L Cys where R8 is a) -(C1-Cg)-alkyl in which alkyl is unsubstituted or substituted independently of one another nce, twice or three times by R1,

b) -(Cg-C14)-aryl in which aryl is unsubstituted or substituted independently of one another nce, twice or three times by R1,

Cc) 4- to 15-membered Het ring in which Het ring is a0 unsubstituted or substituted inedependently of one another once, twice or three times by R1,

d) -(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstituted or substituted independently of ome another once, twice or three times by R1, or as e) hydrogen atom, Yis 3) the radical of the formula V 0) R16 R17) R12 (flo R13 2 R18 R19 where in cas e a)

R12is 1) -(C1-Cg)-alkyl in which alkyl is unsubstituted or substituted independen tly of one another once, twice or three times by R1,

2) -(Cg-C3)-alkyl-(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstituted or substituted independently of one arother once, twice or three times by R1,

3) -(Co-Cg)-alkyl-(Cg-C14)-aryl in which aryl is unsubstituted or substit uted independently of one another once, twice or t-hree times by R1, or

® 4) -(Cp-C3)-alkyl-Het in whi ch Het is urisubstituted or substituted indeependently of one armother once, twice or three tim es by R1, and R13 is 1) -(Cp-C3z)-alkyl-(Cg-C14)—aryl in which alkyl and aryl are each unsubstituted or s ubstituted independently of one another orice, twice or three tiles by R1, or 2) -(Co-Cg)-alkyl-Het in whi ch alkyl and Het are each unsubstituted or substitute=d independently of ore another once, twice or threes times by R1, where in case b) R12is 1) hydrogen atom, 2) -(C1-Cg)-alkyl in which a-lky! is unsubstituted or substituted independently of ones another once, twice or three times by R1, 3) ~(Cp-C3)-alkyl-(Cg-C14)- aryl in which aryl is ure substituted or substituted indespendently of one ars other once, twice or three timees by R1, or 4) -(Cp-C3)-alkyl-Het in whiach Het is une substituted or substituted independently of one an other once, twice or three timees by R1, and R13 is -C H(R8)-R9 where R8 and R9 a_re independently of on e another -(Cg-C14)-aryl or H et in which Het and aryl are each unsubstituted or stibstituted independently of one another ormce, twice or three times by -O-(C1-C4)-alkyl or R1 , and R16, R17, R18 and R19 are id entical or different and are incdependently of one another 1) hydrogen atom, 2) -(C4-Cg)-alkyl, im which alkyl is unsubstituted cr substituted once or twice by R1, 3) halogen, 4) -OH, 5) -NH»,

® 6) -(Cg-Ca)-alkyl-(Cg-C14)-aryl in which alkyl and aryl are each unsubstituted or sub stituted independently of one another once, twice or three times by R1, or 7) -(Cg-Cga)-alkyl-Het ira which alkyl and Het are each unsubstituted or substituted independently of one another once, twice or three times by R1, or R16 and R17 or R18 and R19 form together with the carbon atom to which they are respectively bonded a ring having 3 to 6 ring atoms, or Y~is 4) the radical of the formula VI,

R27 Ni Red — SNC (VI) (Roz "R25 i eo wrhere R24 and R25 are identical or different and are independently of one another 1) hydrogen atom, 2) -(C1-Cg)-alkyl in which alkyl is unsubstituted or substituted once or twice by R1,

3) -(Cp-C3)-alkyl-(Cg-C 14)-aryl in which alkyl and aryl are each unsubstituted or substituted independently of one another once, twice or three times by R1,

4) -(Cp-Ca)-alkyl-Het in which alkyl and Het are eache unsubstituted or substituted independently of one another once, tw ice or three times by R1, or

5) -(Cp-C3)-alkyl-(C3-Cg)-cycloalkyl, or R 24 and R25 form together with the nitrogen atom to which they~ are bonded a rirg having 3 to 8 ring atoms which may, in addition to the nitrog en atom, also comprise one to two additional hetearoatoms from the series oxygen, sulfur or ni-trogen,

R226, R27, R28 and R29 are identical or different and are indepe ndently of one arother 1) hydrogen atom, 2) -(C4-Cg)-alkyl in whic=h alkyl is unsubstituted or sukostituted once or 40 twice by R1,

® 3) halog en, 4) -OH, 5) -NHo 6) -(Cp-CC3)-alkyl-(Cg-Cq4)-aryl in which alkyl and ary! are each unsubstituted or substituted indepemdently of one another once, twice or three times by R1, or 7) -(Co-CC3)-alkyl-Het in which alkyl an d Het are each unsubstituted or substututed independently of one armother once, twice or three t imes by R1 ,or R26 and R27 or R2 8 and R29 form together with the carbon atom to which they are respectively bornded a ring having 3 to 6 ring atoms, Zis 1) hydro gen atom, 2) -(C1-CCp)-alkyl, 3) -(C1—Cpg)-alkyl-OH, 4) -(Co-C4)-alkyl-(C3-Cg)-cycloalkyl, 5) -(C1-C)-alkyl-O-C(O)-O-R1, 6) -(CH2=»)~(Cg-C44)-aryl in which aryl is unsubstituted or substituted independently of one another once, twice Or three times by R1, and r &s the integer zero, 1,2or 3, or 7) -(CHz=)s-Het in which Het is unsubstituted or substituted independent! y of one another once, twice or three times by R1, and s is the integer zero, 1, 2 or 3.

2. A compound of the formula la, as claimed in claim 1, where X SH N=Y (a) z—0 UNF Uis 1) hydrocgen atom, 2) -(Cq-Cg)-alkyl, 3) -(C3-C¢)-cycloalkyl, 4) fluorin e, 5) -O-CF gor

® 6) -CF3,

Xis the radical of the formula ll in which m is the integer zero or 1,

Alis 1) -(CH2)n- in which nis the integer 1, 2 or 3, or

2) -O-(CH2)p- in which n is the integer zero, 1, 2 or 3,

A2is 1) 4- to 15-membered Het ring in which Het ring is selecteed from the group of acridinyl, azepinyl, azetidiryl, aziridinyl, benzimidazaalinyl, bernzimidazolyl, carbolinyl, quinazolinyl, quinolinyl, 4H-quinoli=inyl, qui noxalinyl, quinuclidinyl, chromaryl, chromenyl, cinnolinyl, deca-

hydiroquinolinyl, imidazolidinyl, imid azolinyl, imidazolyl, 1H-incdazolyl, ind olinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isoctkromanyl, iso indazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazeolyl), iso thiazolidinyl, 2-isothiazolinyl, isothiazolyl, isoxazolyl, isoxaz=olidinyl, 2- iso xazolinyl, morpholinyl, naphthyri dinyl, octahydroisoquinolirayl,

oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadia zolyl, 1,3s,4-oxadiazoly!, oxazolidinyl, oxa=olyl, pyrimidinyl, phenanttridinyl, phesnanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, p henoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purynyl, pyran—yl, pyrazinyl, pyr-oazolidinyl, pyrazolinyl, pyrazoly’|, pyridazinyl, pryidooxazoRyl,

pyr-idoimidazolyl, pyridothiazolyl, py ridothiophenyl, pyridinyl, peyridyl, pyr-imidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyi, tetr—ahydroisoquinolinyl, tetrahydroq uinolinyl, tetrahydropyridinayl, 6H-1,2,5- thiaadazinyl, 1,2,3-thiadiazolyl, 1,2,4 -thiadiazolyl, 1,2,5-thiadia=olyl, 1,3,4- thizadiazolyl, thianthrenyl, thiazolyl, £hienothiazolyl, thienooxaz oly,

thieanoimidazolyl, thiomorpholinyl, triazinyi, 1,2,3-triazolyl, 1,2, 4-triazolyl, 1,2 ,5-triazolyl, 1,3,4-triazolyl and xanthenyl and in which the Het ring is sulostituted by an amino group and may additionally be substi tuted ind ependently of one another once, twice or three times by a -(C4-C3)- alk=yl, halogen, -CF3 or -O-CF3,

2) -(C1-Cg)-alkyl-NH»o or 3) -(C3-Cg)-cycloalkyl-NHo,

Yis 1)t he radical of the formula ill where a) A3 is -(C3-Cg)-cycloalkyl or —(C2-Cg)-alkynylene in which cycloalkyl or alkylnylene is unsubstitutexd or substituted independently of one

® a nother once, twice or three timess by -O-R10 or R1, M4 is-N(R2)2- in which R2 is as defined below, and the two R2 radicals are defined independerw tly of one another, M5 is absent and o is the integer zero or 1, and R10 is hydrogen atom, -(C1-Cg) -alkyl or phenyl,

b) M3 is -(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstituteed or s=ubstituted independently of one another once, twice or three times »y-0-R10 or R1,

Ad is-N(R2)-, and M5is a)l) -C(O)-R3, a)2) -C(O)-N(R4)-R5, a)3) -(SO92)-R6, or a) -C(O)-O-R7, © is the integer 1, and [> is the integer 1,

c) Al is cyclic amine from the group of propylamine, azetidinee, pyrrolidine, piperidine, azepaness or azocanes, in which cyclic amine iss unsubstituted or substituted independently of one anothear once, twwice or three times by R1,

A\4 and AS are as defined under b), v-vhere AS is bonded to the N atom of A3, © is the integer zero, and pP is the integer zero or 1, or d) Ais -(CH2)q-(Ce-C14)-aryl in which aryl is selected from the group Of phenyl, naphthyl, anthry! or fleuorenyl and is unsubstitute-d or Ssubstituted independently of one another once, twice or three times by R1, Ad and A5 are as defined under b) oO is the integer zero or 1, and is the integer 1, and is the integer zero, 1, 2 or 3,

e) AJ is -(CH2)-Het in which Het i=s as defined above and is unsubstituted or substituted independently of one another once, twice or three times by =O or R11,

A\4 and A5 are as defined under b),

® 0 iss the integer zero or 1, p iss the integer 1 and r iss the integer zero, 1, 2 or 3, f) A3is -(CH2)q-(Ce-C14)-aryl in wh ich is aryl is unsubstituted or sun bstituted independently of one &another once, twice or tharee times by~ R1, A4- is -O-, ASe is -(Cg-C14)-aryl in which aryl i s unsubstituted or substituted incdependently of one another once, twice or three times bw R1, o and p are the integer 1 and q i-s the integer zero, 1, 2 or 3, a9) -CH(phenyl)-phenyl, where R1 is a) -(Cg-C14)-aryl in which aryll is as defined above ancl where anwyl is unsubstituted or is substitut ed independently of one- another on ce, twice or three times by -(C1—Cg)-alkyl, -(Co-C4)-alky |-(C3-Cg)- cyecloalkyl, -CF3, =O, -O-CF3 or halogen b) 4- to 15-membered Het ring in which Het is as defired ab ove, c) -(C1-Cg)-alkyl, d) -(C3-Cg)-cycloalkyi, e) -CF3, f) -O-CF3 or a) halogen, where R22 is a) -(Ce-C14)-aryl in which aryl is as defined above and is unsubstituted or substituted independently of one another once, twice or three times toy R1, b) -(C1-Cg)-alkyl in which alkyl is unsubstituted or submstituted independently of one anoth er once, twice or three t imes by R1, Cc) -(C3-Cg)-cycloalkyl in whick cycloalkyl is unsubstituted or substituted independently cof one another once, twice or on gr2006/ 0760 ® three times by R1, d) -CF3 or e) hydrogen atom , where R3, R6 and R7 are ide=ntical or different is independently of one another a) -(C1-Cg)-alkyl i n which alkyl is unsubstituted or substituted independently of one another once, twice or &hree times by R1,

b) -(Cg-C14)-aryl in which aryl is as defined above and is unsubstituted oer substituted independently of one another once, twice or t hree times by R1,

c) 4- to 15-membe=red Het ring in which Het ringm is as defined above and is ursubstituted or substituted independently of one another one, twice or three times by R1 ,

d) -(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstituted or substituted indexpendently of one another onc e, twice or three times by R1, or e) hydrogen atom,

where R4 and R5 are identical or different is independently of one another a) -(C1-Cg)-alkyl or -(C,-Cqo)-alkenyl, in which allikyl or alkenyl is unsubstituted or substituted independently of one another once, twice or three times by R1,

b) -(Cg-C14)-aryl im which ary! is as defined abo=ve and is unsubstituted or= substituted independently of one another once, twice or three times by R1,

c) 4- to 15-membesred Het ring in which Het ring is as defined above and is un substituted or substituted independently of one another once, twice or three times by R1,

d) -(C3-Cg)-cycloalkyl in which cycloalkyl is unsumbstituted or substituted indepoendently of one another once, twice or three times by R1, or e) hydrogen atom, or

R4 and RS form together with the nitrogen atom to which thesy are bonded a ring having 3 to 8 ring atoms selected from the group of pr-opylamine, azetidine, pyrrolidine, piperidin e, azepanes, azocanes, azepiine, dioxazole,

PS 82 dioxazine, 1,4-diazepan ee, 1,2-diazepine, 1,3-diazepin e, 1,4-diazepine, imidazole, imidazoline, i midazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-i-soxazoline, ketopiperazine, morphol ine, [1,4]Joxazepane, oxazole, piperazine, pyrazine,

pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridines, pyrimidine, pyrrole, pyrrolidinone, pyrroline, tetrahydropyridine, thiazole, thiadiazole, thiazolidine, thiazoline, t hiomorpholine, 1,2 3-triazine, 1,2,4-triazine, 1,3,5- triazine, 1,2,3-triazole or 1,2,4-triazole,

Y is 2) the radical of the formula IV where formula IV is a co mpound from the group of azetidin-2-one, pyrrolidin-2-one, piperidin-2-cne, azepan-2-one and azocan-2-one and iss substituted on the nitrogen eatom in each case by R8, where R8 is a) -(C1-Cg)-alkyl in which alkyl is unsubstituted or substituted independexntly of one another once, twicze or three times by R1,

b) -(Ce-C14)—aryl in which aryl is as definecd above and is unsubstituted or substituted independermtly of one another once, twice or three times by R1,

c) 4- to 15-m embered Het ring in which He=t ring is as defined above and is unsubstituted or substitute=d independently of one another once, twice or three times toy R1,

d) -(C3-Cg)-cycloalky! in which cycloalkyl is unsubstituted or substituted independently of one anothe r once, twice or three times by R1, or e) hydrogen atom,

Yis 3) the radical of the formula V, where in case a) R12is 1) -(C1-Cg)-alkyl in which alkyl is unsubstit-uted or substituted independently of one another once, twicse or three times by

R1,

2) -(Cg-Cg)-a lkyl-(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstitut ed or substituted independently of one another once, twice= or three times by R1,

® 3) -(Cp -Ca)-alkyl-(Cg-C14)-aryl in which aryl is as defined abowe and is unsubstituted or substituted independently of one another once, twice or three times by R1, or 4) -(Cp -C3)-alkyl-Het in which Het is a s defined above and is unsubstituted or substituted indepemndently of one another once, twice or three times by R1, ard

R13 is 1) -(Cp -C3)-alkyl-(Cg-C14)-aryl in which alkyl and aryl is as defirmed above and are each unsubstituted or substituted inde pendently of one another once, twice or three times by”

R1, or

2) -(Cp -Cg)-alkyl-Het, in which alkyl arnd Het are as defined abowe and are each unsubstituted Or substituted inde pendently of one another once, twice or three times by= R1, or in case b) R12 is 1) hydrogen atom,

2) -(Cq -Cg)-alkyl in which alkyl is unsubstituted or substituted inde pendently of one another once, twice or three times by” R1,

3) -(Cp -C3)-alkyl-(Cg-C14)-aryl in which aryl is unsubstituted or subsstituted independently of one armother once, twice or threex times by R1, or

4) -(Cp -C3)-alkyl-Het in which Het is u nsubstituted or subsstituted independently of one an other once, twice or three times by R1, and

R13 is -CH(R8)-RS where R8 and R9 are indepermdently of one another - (Ce-C14)-aryl or Het in which Het and aryl are each as defined above and are unsubstituted or substituted independently of one another once, twice or three times by -O-(C1-C4)-alkyl or R1, and

R16, R17, R18 and R19 are identical or different and are= independently of one another

1) hydrogen atom, 2) -(C1-Cg)-alkyl in which alkyl is unsubstitute=d or substituted once cor twice by R1 ,

® 3) halogen,

4) -OH,

5) -NH>,

6) -(€Cg-Cg)-alkyl-(Cg-C14)-aryl in which alkyl and aryl is as definead above and are each unsubstituted or substituted independently~ of ore another once, twice or three times by R1, or

7) -(<Cp-C3)-alkyl-Het in which alkyl and Het is as defined above a nd ar-e each unsubstituted or substituted independently of one another orice, twice or three times by R1, or

R16 and R17 or R18 and R19 form together with tthe carbon atom to which tiey are respectively bonded a ring having 3 to 6 ring atoms from the groupo of cyclopropyl, cyclobutyl, cyclopentyl or cyclobexyl, or Yis 4) the radical of the formula VI, where R24 and R25 are identical or different and are inde=pendently of one another

1) hwdrogen atom,

2) -(<€C1-Cg)-alkyl in which alky! is unsubmstituted or substituted once or twice by R1,

3) -(€Cp-Ca)-alkyl-(Cg-C14)-aryl in which alkyl and aryl is as defined aboove and are each unsubstituted or substituted independently of ore another once, twice or three times by R1,

4) -(€Cg-C3)-alkyl-Het, in which alkyl and Het is as defined above and ar-e each unsubstituted or substituted independently of one anther orice, twice or three times by R1, or

5) -(€C-C3)-alkyl-(C3-Cg)-cycloalkyl, or

R24 and R25 fosrm together with the nitrogen atom to which they are bonded a ring having 3 to 8 ring atoms from the group of progoylamine, azetidine, pyrrolidine, pipe=ridine, azepanes, azocanes, azepire, dioxazole, dioxazine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-di azepine, imidazole, imidazoline, imi«azolidine, isothiazole, isothiazolidime, isothiazoline, isoxazole,

isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine, [1,4]oxazepane, oxazole, piperazine, pyrazine, pyrazole, pyrazoline, pyrazoliciine, pyridazine, pyricline, pyrimidine, pyrrole, pyrrolidino ne, pyrroline, tetrahydropyridime, thiazole, thiadiazole, thiazolidines, thiazoline, thiomorpholire, 1,2,3-triazine, 1 ,2,4-triazine, 1,3,5-triazine, 1,2,3-trizazole or 1,2 4-triazole,

® 85

R26. R27, R28 and R29 are identical or different and are indepe-ndently of one anot her 1) hydrogen atom, 2) -(Cq-Cg)-alkyl in whic h alkyl is unsubstituted or su bstituted once or twice by R1, 3) halogen, 4) -OH, 5) -NHo, 6) -(Cg-Cg3)-alkyl-(Cg-Cq 4)-aryl in which alkyl and aryl is as defined above and are each wansubstituted or substituted independently of one another once, twi ce or three times by R1, or 7) -(Cp-Cg)-alkyl-Het in which alkyl and Het is as def’ined above and are each unsubstitute=d or substituted independently of one another once, twice or three ti mes by R1, or R26 and R27 or R28 and R29 form together with the carbon ato.m to which they are respectively bonded a ring havirg 3 to 6 ring atoms from the= group of cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, Zis 1) hydrogen atom, 2) -(Cq-Cg)-alkyt, 3) (C3-Cg)-cycloalkyl, 4) (C1-C1)-alkyl-O-C(3)-0O-R1, 5) -(CH2)~(Cg-C14)-ary 1in which aryl is as defined above and is unsubstituted or substituted Endependentiy of one anothemr once, twice or three times by R1, and ris the integer zero, 1, 2 or 3, or 6) -(CHg)g-Het in which Het is as defined above and is unsubstituted or substituted independently of one another once, twice cr three times by R1, and s is the integer zero, 1, 2 or 3.

3. A co mpound of the formula la as claimed in claims 1 or 2, where Uis hydrogen atom, -CF3, fluorine or ~CH3, X is the radical of the formula | in which mis the integer 1, Allis 1) -(CHg)-, 2) -O-(CHaz)n- in which ra is the integer zero or 1, or

® 86 3) cavalent bond, A2is 1) aminopyridyl in which aminopyridyl is unsubstituted or substituted independently of one another once, twice or three times toy -(C4-Cg)-alkyl, halogen or —-CHg3,

S 2) aminothiazolyl in which aminothiazoly! is unsubstituted or substituted independently of one another once, twice or three times by -(C4-Cg3)-alky!, halogen or ~CH3,

3) -(C4- Cg3)-alkyl-NH»o or 4) -(C3-Cg)-cycloalkyl-NH>, Y”is 1) the radical of the formula lll where a) A3 is -(C3-Cg)-cycloalkyl or (C2-Cg)-alkynylene in which cycloalkyl or alkynylene is unsubstituted or substituted independent ly of one another once, twice or three times by R1, Ad is -N(R2)2- in which R2 is as defined below, and the two R2 radicals are defined independently of one another, AS is absent and o is the integer zero or 1, b) A3 is -(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstitu ted or substituted independently of one another once, twice or three times by R1, Ad is—N(R2)- , and ASis a)1) -C(O)-R3, a)2) -C(O)-N(R4)-R5, a)3) -(S02)-R6 or a4) -C(O)-O-R7, o is the integer 1, and p is the integer 1, c) A3 is cyclic amine having 3 to 8 ring atoms in which cycliec amine is unsubstituted or substituted independently of one anothe r once, twice or three times by R1, A4 and AS5 are as defined under b), where A5 is bonded to the N atom of A3, o is the integer zero, and p is the integer zero or 1, or

® d) A3 is -(CH2)q-(Cp-C14)-aryl in which aryl is unsubstituted or substituted independently «f one another once, twicee or three times by R1, A4 and A5 are as defined winder b), o is the integer zero or 1, and p is the integer 1, and q is the integer zero, 1, 2 or 3, e) A3 is -(CH»9)-Het in which Het is pyrrolidine, benzot hiophene or piperidine, which is unsubsstituted or substituted independently of one another once, twice or three times by =O or R1 A4 and A5 are as defined under b), o is the integer zero or 1, p is the integer 1 and ris the integer zero, 1, 2 ox 3, f) A3 is -(CH2)q-phenyl in which phenyl is unsubstituted or substituted independently of one another once, twice or three tirmes by R1, Ad is -O-, AS is phenyl, in which pheryl is unsubstituted or sutostituted independently of one another once, twice or three tirmes by R1, o and p are the integer 1 a nd q is the integer 1 or 2, where R1 is a) phenyl, where phen yl is unsubstituted or subsstituted independently of one another once, twice of three tirnes by -(C1-C4)-alkyl, b) triazolyl or pyridinyl, c) -(Cq-Cy)-alkyl, d) -(C3- Cg)-cycloalkyl , e) -CF3, f) -O-CF3, a) fluorine or h) chlorine, where R2 is a) phenyl in which phe nyl is unsubstituted or subostituted

® independently of on e another once, twice or three times by R1,

b) -(C1- Cg)-alkyl in which alkyl is unsubstituted or stubstituted independently of on € another once, twice or three times by R1,

Cc) -(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstituted or substituted independently of one another once, twice or three times by R1,

d) -CF3 or e) hydrogen atom, where R3, R6 and R7 are identica | or different are independent!wy of one another a) -(C1-Cg)-alkyl in which alkyl is unsubstituted or su bstituted independently of one another once, twice or three times by

R1,

b) -(Cg-C14)-aryl in whrich aryl is unsubstituted or sulostituted independently of one another once, twice or three times by R1,

c) 4- to 15-membered Het ring in which Het ring is unsubstituted or sub stituted independently of one another once, twice or three times by R1,

d) -(C3-Cg)-cycloalkyl i n which cycloalkyl is unsubstit uted or substituted independently of one another once, twi ce or three times by R1, or e) hydrogen atom, where R4 and RS are identical or different are independently of one another a) -(C1-Cg)-alkyl or (C, -Cg)-alkenyl, in which alkyl or =alkenyl is unsubstituted or substituted independently of one another once, twice or three gimes by R1,

b) -(Cg-C14)-aryl in whi ch aryl is unsubstituted or submstituted independently of ones another once, twice or three times by R1,

Cc) 4- to 15-membered Het ring in which Het ring is unsubstituted or substituted independently of >

° once, twice or three times by R1,

d) -(C3-Cg)-cycloalkyl i nm which cycloalkyl is unsubstituted or substituted independently of one another once, twice or three times by R1, om e) hydrogen atom, or R4 and R5 form together with the mitrogen atom to which they are bonded a ring derived from azetidine, pyrrolidine, piperidine, azepames, azocanes, azepine, dioxazole, dioxazine, 1,4~ diazepane, 1,2-diazepinez, 1,3- dliazepine, 1,4-diazepine, imidazole, imidazoline, imidazoiidlline, isothiazole, issothiazolidine, isothiazoline, isoxa==zole, isoxazoline, isoxazolidine, 2- issoxazoline, ketopiperazine, morph oline, [1,4Joxazepane, oxazole, piperazine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyr-idazine, pyridine, pyrimidine, pyrrole, pyrrol@dinone, pyrroline, tetrah=ydropyridine, thiazole, thiadiazole, thiazolidine, thiazoline, thiomorpholine=, 1,2 3-triazine, 1 ,2,4-triazine, 1,3,5-triazine, 1,2,3-&riazole or 1,2,4-triazole, Yis 2 )the radical of the formula IV selected from the group of aazetidin-2-one, p yrrolidin-2-one or piperidin-2-one, where the radical is sub-stituted on the nitrogen atom in each case by R8, where R8 is a) -(C4-Cg)-alkyl in which alkyl is unsubstituted or subsstituted independently of one anothear once, twice or three tirmes by R1,

b) phenyl in which phenyl is un substituted or substituted independently of one another once, twice cor three times by R1,

c) hydrogen atom or d) -(C3-Cg)-cycioalkyl in which cycloalkyl is unsubstitute=d or substituted independently of one another once, twice2 or three times by R1,

Yis 3) the radical of the formula V where in the case a)

R12 is 1) -(C4-Cg)-alkyl in whic=h alkyl is unsubstituted oor substituted independently of one anothe=r once, twice or three tines by R1,

2) -(Cp-Cg)-alkyl-(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstituted or substituted independently of one aneother once, twice or three times by R1, cer 3) -(Cp-C3)-alkyl-phenyl in which phenyl is unsubstituted or substituted independently of one another once, twice or three times by R1, and

° 0 pn06/ ©7668 R13 is 1) -(Cp-C3)-alkkyl-phenyl in which alkyl and phen=yl are each unsubstituted or substituted independently of one armother once, twice or three timers by R1, or 2) -(Co-C3)-alkyl-pyridyl in which alkyl and pyridwy! are each unsubstituted or substituted independently of one an other once, twice or three times by R1, or in the case b) ‘ R12is 1) hydrogen atom, 2) -(C1-Cg)-alkyl in which alkyl is unsubstituted or substituted independently of o ne another once, twice or three tirmes by R1, 3) -(Cp-C3)-alkyl-phenyl in which phenyl is unsubstituted or substituted independently of one another once, twice or three times by R1, or 4) -(Cg-C3)-alkyl-pyridy! in which alkyl and pyrid~y! are each unsubstituted or substituted independently of one an other once, twice or three time s by R1, and R13 is -CH(R8)-R9 wherez R8 and R9 are independently of cone another phenyl or pyridyl in which phenyl or pyridyl are each unsubstituted or substituted inde pendently of one another once, twice or three times by -O-(C1-C4)-alky! or R1, and R16, R17, R18 and R19 are identical or different and are independently of one another 1) hydrogen atom, 2) -(C4-C3)-alkyl in wrhich alkyl is unsubstituted or subs tituted once or twice by R1, 3) fluorine, 4) -OH, 5) -NHo or 6) -(Cp-C3)-alkyl-phe nyl, in which alkyl and phenyl are «each unsubstituted or substituted independently of one an other once, twice or three time sby R1, or Y is 4)the radical of the formula VI, where R24 and R25 are identical or diff erent and are independently of on e another 1) hydrogen atom,

® 2) -(C1-Cg)-alkyl in whiech alkyl is unsubstituted or substituted once or twice by R1, 3) -(Cg-Cga)-alkyl-pheny~l in which alkyl and phenyl! are each unsubstituted or substituted independently of orx e another once, twice or three times boy R1, or 4) -(Cp-C3)-alkyl-(C3-Ces)-cycloalkyl, or R2 6, R27, R28 and R29 are identical or different and are inde goendently of one another 1) hydrogen atom, 2) -(C1- C3)-alky! in which alkyl is unsubstituted or substituted once or twice by R1, 3) fluorine, 4) -OH, 5) -NHo or 6) -(Co-C3)-alkyl-pheny~lin which alkyl and phenyl =are each unsubstituted or subsstituted independently of on e another once, twice or three times boy R1, and Z iss hydrogen atom or (C1-Cg4)-alkyvl.

4. A compound of the formula la as claimed in claims 1 or 2, where Uiss hydrogen atom, X is the radical of the formula ll in which m i s the integer 1, A1 is -(CHbg)-, A2 is aminopyridyl in which aminopyridyl is unsubstituted or substituted independently of one anothear once, twice or three times by halogen or -CH3, Y is 1) the radical of the formula [ll where a) A3 is -(C3-Cg)-cycloalkyl in which cycloalkyl is unsubsti—tuted or substituted indezpendently of one another once, twice or three times by R1 , and A4 and A5 are absent, b) A3 is -(C2-C4)-alkynylene in which alkynylene is unsubstituted or subwstituted independently of one arother once, twice or three times by R1, and A4 and AS are absent,

® 92 c) A3 is cyclic amine having 3 to 8 rimg atoms in which cyclic amine is unsub stituted or substituted independent! y of one another once, twice or t hree times by R1, and A4 and AS are absent, d) A3 is -(CH2)q-pheny! in which phe ny! is unsubstituted or substitute d indepe=ndently of one another once, twice or three times by R1, A4 is —N(R2)- in which R2 is as defined below AS5is a)1) -C(O)-R3, a)2) -C(O)-N(R4)-R5, a)3) -(SO2)-R6 or a)y4) -C(O)-O-R7, ois thes integer 1, and p is thee integer 1, and q is thee integer zero, 1, or 2, e) A3 is -(CH2)~Het in which Het is a pyrrolidine or piperidine which is unsubstituted or substituted independently of one another once, twice or three times by R1, A4 is absent and A5 is as defined under d ), where A5 is bonded to the nitrogen atom of A3, p is the integer 1, and ris the integer zero, 1, 2 or 3, f) A3 is -CH2-phenyl, where phenyl iss unsubstituted or substituted indepe ndently of one another once, twice ©r three times by R1, Ad is -O-, AS is phenyl, where phenyl is unsubstitut ed or substituted independently of one anothe r once, twice or three times by R1, where R1 is a) phenyl where phenyl is unsubstituteed or substituted independently of one another once, twice or three times by -(C1-C4)-alkyl, b) triazolyl or pyridinyl, Cc) —(C1-C4)-alkyl, d) —(C3-Cg)-cycloalkyl, e) —CF3, f) —~0-CF3,

. : g) fluorine or i) chlo rine, where R2 iss hydrogen atom or -(C1-C3)-allyl in which is alkyl is unssubstituted or substituted independently of one another once, twice or three times by R1, where R3, R6 and R7 are identical or different are i ndependently of one another a) -(C1 -Cg)-alky! in which alkyl is unsubstituted or substituted indeependently of ore another once, twice or three tirmes by R1, b) pheryl in which phenyl is unsubstitutezd or substituted independently of one another once, twice or three times by R1, c) hydreogen atom, or d) -(C3—Ceg)-cycloalkyl in which cycloalky 1 is unsubstituted or substituted independently of one another once, twice or three times by R1, where R4 asd R5 are identical or different ar=e independently of one arother a) -(C4—Cg)-alkyl or -(C,-Cs)-alkenyl, in which alkyl or alkenyl is urisubstituted or su bstituted independently of one arother once, twice or three= times by R1, b) phen-yl in which phenyl is unsubstituteed or substituted independ ently of one another once, twice or three times by IR1, Cc) hydrogen atom, or d) -(C3-#Cg)-cycloalkyl in which cycloalkyl is unsubstituted or substituted indep-endently of one another once, twice or three times by R1, Yis 2) the radical of a pyrrolidin-2-one whe=re the radical is substituteed in each case by R8 on the nitrogen atom, where R8 iis a) -(C4-Cg)-alkyl in which alkyl is unsubstituted or substituted inde pendently of one2 another once, twice or three tim es by R1, b) phenyl in which phenyl is unsubstituted or substituted independently of one anoth er once, twice or three times by R1, c) -(C3-Cg)-cycloalky! in which cycloalkyl is unsubstituted or substituted independently of one another once, twi ce or three times by R1, Yis 3)the radical of the formula V where R12 is hydrogen atom or -(C1-Cg)-alkyB® in which alkyl is unsubstituted or substituted independently of one another once, twice or three tines by R1, and

® 94 R13 is -CH(R8)-R9 where R8 and R39 are independently of one another phenyl or pyridyl in whi ch pyridyl and phenyl are each wunsubstituted or substituted independent! y of one another once, twice or three times by R1, and R16, R17, R18 and R19 are identical or different ame d are independently of one another 1) hydroegen atom, 2) -(C1-C3)-alkyl in which alkyl is unsubsstituted or substituted twice by R1, or 3) -(Co- Ca)-alkyl-phenyl, in which alkyl &and phenyl are each unsubmstituted or substituted independently of one another once, twice =or three times by R1, and Zis 1) hydrogen atom, 2) ~(C1-Ce)-alky, 3) -(C1-Cp)-alkyl-OH, 4) -(Co-C4)-alkyl -(C3-Cg)-cycloalkyl, or 5) -(C1-C1p)-alkyl-O-C(0)-O-(C3-Cg)-cy cloalkyl.

5. A compound of the formula la as claimed in one or rmore of claims 1 to 4, where Uis hydrogen ato m, X is the radical of the formula Il in which m is the integer 1, Alis -(CH»)-, A2is the radical N which is unsubsstituted or substituted independently of ones another once, twice or three tirmes by F, CI, Br, | or -CH3, Yis 1)theradical of the formula lll where a) A3 is -(C3-Cgg)-cycloalkyl in which cycloalkyl iss unsubstituted or substitutezd independently of one another once, twice or three times by R1, and A4 and AS are absent, b) A3 is -(C2-C4 )-alkynylene in which alkynylene= is unsubstituted or substituted independently of one another once, twice or three times by R1, and A4 and AS are absert, c) A3 is cyclic armine having 3 to 6 ring atoms in which cyclic amine is unsubstituted or subsstituted independently of one an«other once, twice or three

95 n-2006/ 07668 ® times by R1, amd A4 and A5 are absent, d) A3 is -(CCHp)g-phenyl in which phenyl is unsubstituted or substituted independently «of one another once, twice or th ree times by R1, A4 is -N(R2)- im which R2 is as defined below, AbSis a)l) -«C(0)-R3, a)2) -«C(O)-N(R4)-R5, a)3) -«SO2)-R6 or a)4) -cC(O)-0-R7, ois the integer 1, p is the integer 1, and q is the integer zero, 1, or 2, e) A3 is -(CHp)-Het in which Het is a pyrrolidine or piperidine which is unsubstituted o=r substituted independently of osne another once, twice or three times by R1, A4 is absent armd AS is as defined under d), wh ere A5 is bonded to the nitrogen atom of A3, p is the integer 1, and ris the integer =ero, 1, 2 or 3, f) A3 is -CHi2-phenyl, where phenyl is unsubstituted or substituted independently of one another once, twic e or three times by R1, Ad is -O-, A5 is phenyl, vvhere phenyl is unsubstituted or substituted independenti-y of one another once, twice or three times by RE, where R1 is a) phenyl where phenyl is unsubstituted or substituted independentiy= of one another once, twice or three times by -(C1-C4)-alkyl, b) pyridyl or— tetrazolyl, c) -(C1-C4)—alkyl, d) -(C3-Cg)—cycloalkyl, e) -CF3, f) -O-CF3, a) fluorine oer i) chlorine,

® 96 wher-e R2 is hydrogen atom or -(C1-C3)-alkyl in which is alkyl is unsubst ituted or subs tituted independently of one another once, twice or three times by RR1, where R3, R6 and R7 are identical or dif ferent are independently of one another a) (C1-Cg)-alkyl in which alkyl is unsubstituted or substituted indepe=ndently of one znother once, twice or three times by R1, b) phenyl in which phenyl is unsubstituted or substituted independertly of one another once, twice or three times by R1, or Cc) -(C3-Cg)-cycloalkyl, in which cycloalkyl is unsubstituted or substit uted indepoendently of one another once, twice or three times by R1, where R4 and R5 are identical or different are independently of one another a) (C1-Cg)-alkyl or -(C,-Ceg)-alkenyl, in which alkyl or -(C,-Cg)-alkenywl is unsubstituted or substituted independently of one another once, twice or three timess by R1, b) phenyl in which phenyl is unsubstituted or substituted independertly of one another once, twice or three times by R1, Cc) hydrogen atom, or d) -(C3-Cg)-cycloalkyl in which cycloalkyl is unsubstituted or substituted independently of one another once, twice or three times by R1, Y is 2) the radical of a pyrrolidin-2-one where the radical is substituted in each case by R8 on the nitrogen atom, wher-e R8 is phenyl in which phenyl is unsubstituted or substituted indep endently of one another once, twice or threxe times by R1, Yis 3) the radical of the formula V wh ere R12 fis hydrogen atom or -(C1-Cg )-alkyl in which alkyl is unsubstit uted or substituted independently of one another once, twice or three times by R1, and R13 us -CH(R8)-R9 where R8 and R9 are independently of one arother phen yi or pyridyl in which pyridyl and phenyl are each unsubstituted or saubstituted independently of one another once, twice or three times by R1, R16, R17, R18 and R19 are identical or different and are independently of one another 1) hydrogen atom, 2) -(C4-C3)-alkyl in which alkyl is unsubstituted or substituted once or twice by R1, or 3) -(Cg- C3)-alkyl-phenyl, in which alkyl and phenyl are each unsubsstituted or

® substitutead independently of one another onece, twice or three times b=y R1, and Z is hydreogen atom.

6. A compo und of the formula | as claimed in o ne or more of claims 1 to 5, which is the compeound 3-(6-Amiropyridin-3-yl)-2-(1-cyclohexyl-1H-imi dazol-4-yl)propionic acid, Methyl 3- (6-aminopyridin-3-yi)-2-(1-cyclohexyl—1H-imidazol-4-yl)propionaate, Isopropyl 3-(6-aminopyridin-3-y!)-2-(1-cyclohexyl-1H-imidazol-4-yl)propiomnate, Cyclopropylmethyl 3-(6-aminopyridin-3-yl)-2-(1 -cyclohexyl-1H-imidazol-4 - yl)propiorate, 2-Hydroxwyethyl 3-(6-aminopyridin-3-yl)-2-(1-cy clohexyl-1H-imidazol-4-yl)goropionate, 1-Cycloheaxyloxycarbonyloxyethy! 3-(6-aminopwyridin-3-yl)-2-(1-cyclohexyl -1H- imidazol-=1-yl)-propionate, 3-(6-Amiropyridin-3-yl)-2-(1-cyclopentyl-1H-i midazol-4-yl)propionic ac=id, 3-(6-Amiropyridin-3-yl)-2-(1-piperidin-4-yi-1H-imidazol-4-y!)propionic &cid, 3-(6-Amiropyridin-3-yi)-2-[1-(2-oxo-1-phenylpyrrolidin-3-yl)-1H-imidazeol- 4-yl]propi onic acid, 3-(6-Amiropyridin-3-yl)-2-{1-[(benzhydrylcartoamoyl)methyl]-1H-imida=ol- 4-yl}propi onic acid, Isopropyl 3-(6-aminopyridin-3-yl)-2-{1-[(benzydrylcarbamoyl)methyl]- 1H- imidazol-=4-yl}-propionate, 3-(6-Amirmopyridin-3-yl)-2-{1-[4-(3-phenylureicdo)phenyl]-1H-imidazol-4—yl}propionic acid, 3-(6-Amirmopyridin-3-yl)-2-{1-[2-(1-diphenylac«etylpiperidin-4-y)ethyl]-1 FH-imidazol- 4-yl}-prop ionic acid, 3-(6-Amirmopyridin-3-yl)-2-{1-[2-(1-benzoylpipeeridin-4-yl)ethyl]-1H-imid=azol- 4-yl}propiconic acid, 3-(6-Amirmopyridin-3-yl)-2-[1-(1-benzoylpiperidin-2-yimethyl)-1H-imidaz=ol- 4-yllpropicnic acid, 3-(6-Aminuopyridin-3-yl)-2-(1-{2-[1-(3-phenylpr-opionyl)piperidin-3-yl]eth=y}-1H- imidazol-4-yl)propionic acid, 3-(6-Amin opyridin-3-yl)-2-[1-(1-diphenylacetyl piperidin-3-yimethyl)-1H- imidazol- 4-yl]propiconic acid, 3-(6-Amin opyridin-3-yl)-2-(1-{2-[1-(3-phenylpropionyl)piperidin-4-yl]ethxyl}- 1H- imidazol-4--yl)propionic acid, 3-(6-Amin opyridin-3-yl)-2-{1-[2-(1-phenylacety/ipiperidin-3-yl)ethyl]-1H-i midazol-

® 98 4-yl}propionic aci d, 3-(6-Aminopyridir-3-yl}-2-{1-[2-(1-phenylacetylpipe ridin-4-yl)ethyl]-1H-imidazol- 4-yl}propionic aci d, 3-(6-Aminopyridir-3-yl)-2-{1-[1-(4'-methylbiphenyl-3-carbonyl)piperidin-

4-yimethyl]-1H-inmidazol-4-yl}propionic acid, 3-(6-Aminopyridim-3-yl)-2-[1-(1-benzoylpiperidin-4-yimethyl)-1H-imidazol- 4-yl]propionic acid, 3-(6-Aminopyridir-3-yl)-2-(1-benzhydryl-1H-imidazol-4-yl)propionic acid, 3-(6-Aminopyridim-3-yl)-2-{1-(4-[1,2,4]triazol-1-yl-be nzyl)-1H-imidazol-

4-yl]propionic acid, 3-(6-Aminopyridirm-3-y!)-2-[1-(4-trifluoromethoxyben _zyl)-1H-imidazol-4-yl]propionic acid, 3-(6-Aminopyridir-3-yl)-2-[1-(1,1-dioxo-1H-1,6-benzo[b}thiophen-2-yimethyl)-1H- imidazol-4-yllpropionic acid, 3-(6-Aminopyridire-3-yl)-2-[1-(5-chlorobenzo[b]thiopien-3-yimethyl)-1H-imidazol- 4-yl}-propionic aci d, 3-(6-Aminopyridire-3-yl)-2-{1-[3-(4-fluorophenoxy)be nzyl]-1H-imidazol- 4-yl}propionic acid, 3-(6-Aminopyridin -3-yl)-2-[1-(2-phenoxybenzyl!)-1H-#midazol-4-yl)propionic acid, 3-(6-Aminopyridin -3-y1)-2-[1-(4-phenoxybenzy!)-1H-&midazol-4-yl}propionic acid, 3-(6-Aminopyridin -3-yl)-2-(1-prop-2-ynyl-1H-imidazol-4-yl)propionic acid, 3-(6-Aminopyridin -3-y!)-2-(1-but-2-ynyl-1H-imidazol—4-yl)propionic acid, 3-(6-Aminopyridin -3-y!)-2-[1-(4,4-dimethylcyclohexyl )-1H-imidazol-4-yl]propionic acid, 3-(6-Aminopyridin—3-yl)-2-{1-[(benzhydrylmethyicarb amoyl)methyl}-1H-imidazol- 4-yi}- propionic ac id, 3-(6-Aminopyridin—-3-yl)-2-[1-({[(4-chlorophenyl)phen ylmethyljcarbamoyl}methyl)- 1H- imidazol-4-yl]poropionic acid, 3-(6-Aminopyridin—3-y1)-2-[1-({[bis-(4-methoxyphenyl )methyllcarbamoyl}methyl)- 1H-imidazol-4-yl]p ropionic acid, 3-(6-Aminopyridin—3-yl)-2-{1-[4-(3-propylureido)phen yl]-1H-imidazol-4-yl}propionic acid, 3-(6-Aminopyridin—3-yl)-2-{1-[4-(toluene-4-sulfonylanino)phenyl]- 1H-imidazol- 4-yl}-propionic acid, 3-(6-Aminopyridin- 3-yl)-2-{1-[3-(3-propylureido)benzwyl]- 1H-imidazol-4-yl}propionic acid,

® 99 Er2006/ 078 BE 3-(6-Aminopyridin-3-wl)-2-{1-[3-(3-phenethylureido)benz yl]-1H-imidazol- 4-yl}propionic acid, 3-(6-Aminopyridin-3-wl)-2-{1-[3-(3-benzylureido)benzyl]- 1H-imidazol-4-yl}propioni c acid, 3-(6-Aminopyridin-3-y/1)-2-{1-[3-(3-vinylureido)benzyl]-1H-imidazol-4-yl}propionic acid, 3-(2-Aminothiazol-4-y1)-2-{1-[(benzhydrylcarbamoyl)met hyl]-1H-imidazol-4-yl- : propionic acid, 3-(2-Aminothiazol-4-y~1)-2-[1-({{(4-chlorophenyl)phenylmethyl]carbamoyl}methyl)- 1H-imidazol-4-yl]prop ionic acid, 3-(6-Aminopyridin-3-y~1)-2-{1-[4-(3-tert-butylureido)pheny I]-1H-imidazol-4-yl}- propionic acid, 3-(6-Aminopyridin-3-y-1)-2-{1-[4-(3-benzylureido)pheny!}- 1 H-imidazol-4-yl}propioniac acid or Ethyl 3-(6-aminopyridi n-3-yl)-2-(1-cyclohexyl-1H-imidazo I-4-yl)propionate.

7. A process for preparireg the compound of the formula | as claimed in one or more of claims 1 to 6, whicte comprises a), a compound of the formula Vil Sm (vi) PG—O N where PG1 is a carboxyl protective group, being converted into a compound of the formula | as claimexd in claim 1, b) a compound of the formula | which has been prepared by process a), or a suitable precur sor of the formula | which occurs o wing to its chemical structure in enantiomeric forms being fractionated by salt formation with enantiopure acids or bases, chromatography on chiral stationary phases or derivatization using chi ral enantiopure compounds such a's amino acids, separation of the diasteereomers obtained in this way, and elimination of the chiral auxiliary groups into thes pure enantiomers, or Cc) the compound of the formula | prepared by processes a) or b) being either isolated in free form or, in the case where acidic or basic gyroups are present, converted into physiologically tolerated salts.

® 100

8. As medicament having an effectiv-e content of at least one compound of the formula | as claimed in one or moore of claims 1 to 6 together with a p harmaceutically suitable and phe ysiologically tolerated carrier, additive and/or 0 ther active ingredients and excipients.

9. T he use of the compound of the formula | as claimed in one or rmore of claims 1 tc 6 for producing a medicament for the prophylaxis and therapy of all disorders associated with thromboses, emibolisms, hypercoagulability or fi brotic changes.

10. Tihe use as claimed in claim 9, which is applied to myocardial infarction, angina pe=ctoris and other types of acute coronary syndrome, stroke, pe ripheral vascular di sorders, deep vein thrombosis, pulmonary embolism, embolic or thrombotic ewents caused by cardiac arrhyth mias, cardiovascular events su ch as restenosis following revascularization and amgioplasty and similar proceduress such as stent implantations and bypass operations, or reduction of the risk of t hrombosis fo-llowing surgical procedures as i n knee and hip joint operations , or disseminated in—travascular coagulation, sepsis and other intravascular events “which are asssociated with an inflammation, atherosclerosis, diabetes and tke metabolic syndrome and its sequelae, tumo r growth and tumor metastasis, impairments of thee hemostatic system such as fitorin deposits, fibrotic changes o»f the lung such ass chronic obstructive lung diseasse, adult respiratory distress syrndrome or fibrin de=posits in the eye after eye operations or prevention and/or treamtment of scar fomrmation.