UA73166C2 - Dipeptidilpeptidasa iv inhibitor, pharmaceutical composition on its base - Google Patents

Dipeptidilpeptidasa iv inhibitor, pharmaceutical composition on its base Download PDF

Info

Publication number: UA73166C2
Authority: UA; Ukraine
Prior art keywords: carbonyl; carbonitrile; pyrrolidine; thiazolidine; lysinyl
Prior art date: 2000-04-26

Application number

UA2002108484A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Ferring Bv

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-04-26

Filing date

2001-04-26

Publication date

2005-06-15

2001-04-26 Application filed by Ferring Bv filed Critical Ferring Bv

2005-06-15 Publication of UA73166C2 publication Critical patent/UA73166C2/uk

Links

239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
239000003112 inhibitor Substances 0.000 title abstract description 18
150000001875 compounds Chemical class 0.000 claims abstract description 49
150000003839 salts Chemical class 0.000 claims abstract description 9
208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 9
229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 56
OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 33
ALSCEGDXFJIYES-UHFFFAOYSA-N pyrrolidine-2-carbonitrile Chemical compound N#CC1CCCN1 ALSCEGDXFJIYES-UHFFFAOYSA-N 0.000 claims description 32
239000000203 mixture Substances 0.000 claims description 24
201000010099 disease Diseases 0.000 claims description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
238000000034 method Methods 0.000 claims description 12
125000002560 nitrile group Chemical group 0.000 claims description 10
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 8
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 7
239000008103 glucose Substances 0.000 claims description 7
208000002705 Glucose Intolerance Diseases 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 6
201000009104 prediabetes syndrome Diseases 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 4
125000004434 sulfur atom Chemical group 0.000 claims description 4
206010056438 Growth hormone deficiency Diseases 0.000 claims description 3
230000001363 autoimmune Effects 0.000 claims description 3
208000027866 inflammatory disease Diseases 0.000 claims description 3
201000010065 polycystic ovary syndrome Diseases 0.000 claims description 3
230000002829 reductive effect Effects 0.000 claims description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
125000003282 alkyl amino group Chemical group 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000004432 carbon atom Chemical group C* 0.000 claims description 2
239000000460 chlorine Substances 0.000 claims description 2
229910052801 chlorine Inorganic materials 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000001786 isothiazolyl group Chemical group 0.000 claims description 2
125000000842 isoxazolyl group Chemical group 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000002971 oxazolyl group Chemical group 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000003373 pyrazinyl group Chemical group 0.000 claims description 2
125000003226 pyrazolyl group Chemical group 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
208000023275 Autoimmune disease Diseases 0.000 claims 2
206010036049 Polycystic ovaries Diseases 0.000 claims 1
125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
125000004093 cyano group Chemical group *C#N 0.000 claims 1
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
229910052757 nitrogen Inorganic materials 0.000 claims 1
125000002098 pyridazinyl group Chemical group 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
229910052760 oxygen Inorganic materials 0.000 abstract description 3
229910052739 hydrogen Inorganic materials 0.000 abstract description 2
102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 abstract 1
101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 abstract 1
RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
239000002904 solvent Substances 0.000 description 39
239000000243 solution Substances 0.000 description 38
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
239000012230 colorless oil Substances 0.000 description 25
239000003480 eluent Substances 0.000 description 25
238000003818 flash chromatography Methods 0.000 description 23
239000007787 solid Substances 0.000 description 23
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
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239000012266 salt solution Substances 0.000 description 16
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
239000002253 acid Substances 0.000 description 13
-1 aminoacrylpyrrolidineboronic acids Chemical class 0.000 description 13
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
MPGQQQKGAXDBDN-UHFFFAOYSA-N 1,3-thiazolidin-3-ium;chloride Chemical compound Cl.C1CSCN1 MPGQQQKGAXDBDN-UHFFFAOYSA-N 0.000 description 11
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
229960003104 ornithine Drugs 0.000 description 9
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
239000000047 product Substances 0.000 description 7
QROMHLFLMYDBEQ-UHFFFAOYSA-N pyrrolidine-2-carbonitrile;2,2,2-trifluoroacetic acid Chemical compound N#CC1CCCN1.OC(=O)C(F)(F)F QROMHLFLMYDBEQ-UHFFFAOYSA-N 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 6
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241001190694 Muda Species 0.000 description 6
239000013543 active substance Substances 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
238000002953 preparative HPLC Methods 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 5
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
102100040918 Pro-glucagon Human genes 0.000 description 4
210000001744 T-lymphocyte Anatomy 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 4
AIOMGEMZFLRFJE-UHFFFAOYSA-N 1,3-thiazolidine-4-carboxamide Chemical compound NC(=O)C1CSCN1 AIOMGEMZFLRFJE-UHFFFAOYSA-N 0.000 description 3
RXTRRIFWCJEMEL-UHFFFAOYSA-N 2-chloropyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1Cl RXTRRIFWCJEMEL-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 3
239000004472 Lysine Substances 0.000 description 3
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239000007858 starting material Substances 0.000 description 3
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KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
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NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
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- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Hematology (AREA)
Obesity (AREA)
Immunology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Gynecology & Obstetrics (AREA)
Pregnancy & Childbirth (AREA)
Emergency Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Thiazole And Isothizaole Compounds (AREA)
Pyridine Compounds (AREA)

UA2002108484A 2000-04-26 2001-04-26 Dipeptidilpeptidasa iv inhibitor, pharmaceutical composition on its base UA73166C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB0010188.1A GB0010188D0 (en)	2000-04-26	2000-04-26	Inhibitors of dipeptidyl peptidase IV
PCT/GB2001/001875 WO2001081337A1 (en)	2000-04-26	2001-04-26	Inhibitors of dipeptidyl peptidase iv

Publications (1)

Publication Number	Publication Date
UA73166C2 true UA73166C2 (en)	2005-06-15

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ID=9890560

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2002108484A UA73166C2 (en)	2000-04-26	2001-04-26	Dipeptidilpeptidasa iv inhibitor, pharmaceutical composition on its base

Country Status (29)

Country	Link
US (1)	US7125863B2 (et)
EP (1)	EP1280797B1 (et)
JP (1)	JP2003531204A (et)
KR (1)	KR20020093942A (et)
CN (1)	CN1249056C (et)
AT (1)	ATE279408T1 (et)
AU (1)	AU784007B2 (et)
BR (1)	BR0110021A (et)
CA (1)	CA2407662A1 (et)
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DK (1)	DK1280797T3 (et)
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Families Citing this family (87)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1999038501A2 (en)	1998-02-02	1999-08-05	Trustees Of Tufts College	Method of regulating glucose metabolism, and reagents related thereto
GB0109146D0 (en) *	2001-04-11	2001-05-30	Ferring Bv	Treatment of type 2 diabetes
WO2003002553A2 (en)	2001-06-27	2003-01-09	Smithkline Beecham Corporation	Fluoropyrrolidines as dipeptidyl peptidase inhibitors
IL158923A0 (en)	2001-06-27	2004-05-12	Smithkline Beecham Corp	Fluoropyrrolidines as dipeptidyl peptidase inhibitors
ATE380175T1 (de) *	2001-06-27	2007-12-15	Smithkline Beecham Corp	Pyrrolidine als dipeptidyl peptidase inhibitoren
JPWO2003024942A1 (ja) *	2001-09-14	2004-12-24	三菱ウェルファーマ株式会社	チアゾリジン誘導体およびその医薬用途
GB0125445D0 (en) *	2001-10-23	2001-12-12	Ferring Bv	Protease Inhibitors
GB0125446D0 (en) *	2001-10-23	2001-12-12	Ferring Bv	Novel anti-diabetic agents
AU2002360453C1 (en) *	2001-11-26	2009-06-18	The Brigham And Women's Hospital, Inc.	Methods for treating autoimmune disorders, and reagents related thereto
JP4771661B2 (ja)	2001-11-26	2011-09-14	トラスティーズオブタフツカレッジ	Ｐｏｓｔ−プロリン開裂酵素の擬ペプチド性阻害剤
ATE309988T1 (de) *	2002-02-13	2005-12-15	Hoffmann La Roche	Neue pyridin- und quinolin-derivate
EP1556362B1 (en) *	2002-10-18	2008-03-26	Merck & Co., Inc.	Beta-amino heterocyclic dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
US7550590B2 (en) *	2003-03-25	2009-06-23	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
WO2004089362A1 (en) *	2003-04-11	2004-10-21	Novo Nordisk A/S	2-cyanopyrroles and their analogues as ddp-iv inhibitors
ZA200508439B (en)	2003-05-05	2007-03-28	Probiodrug Ag	Medical use of inhibitors of glutaminyl and glutamate cyclases
DE602004026712D1 (de)	2003-05-05	2010-06-02	Probiodrug Ag	Medizinische verwendung von hemmern von glutaminyl und glutamatcyclasen
CN1784220B (zh)	2003-05-05	2011-08-03	前体生物药物股份公司	谷氨酰胺酰基和谷氨酸环化酶效应物的应用
JP2007511467A (ja)	2003-05-14	2007-05-10	タケダサンディエゴインコーポレイテッド	ジペプチジルペプチダーゼインヒビター
US6995183B2 (en)	2003-08-01	2006-02-07	Bristol Myers Squibb Company	Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods
WO2005016911A1 (en) *	2003-08-13	2005-02-24	Takeda Pharmaceutical Company Limited	4-pyrimidone derivatives and their use as peptidyl peptidase inhibitors
US7678909B1 (en)	2003-08-13	2010-03-16	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
US7169926B1 (en)	2003-08-13	2007-01-30	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
HU227684B1 (en)	2003-08-29	2011-11-28	Sanofi Aventis	Adamantane and azabicyclo-octane and nonane derivatives and their use as dpp-iv inhibitors
EP1699777B1 (en) *	2003-09-08	2012-12-12	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
CN102302781A (zh)	2003-10-15	2012-01-04	前体生物药物股份公司	谷氨酰胺酰基环化酶效应物和谷氨酸环化酶效应物的应用
EP2338490A3 (en)	2003-11-03	2012-06-06	Probiodrug AG	Combinations useful for the treatment of neuronal disorders
CN1905876B (zh)	2003-11-17	2010-06-09	诺瓦提斯公司	二肽基肽酶iv抑制剂的用途
NZ548351A (en)	2004-01-20	2009-08-28	Novartis Ag	Direct compression formulation and process
EP1713780B1 (en)	2004-02-05	2012-01-18	Probiodrug AG	Novel inhibitors of glutaminyl cyclase
US7732446B1 (en)	2004-03-11	2010-06-08	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
UA85871C2 (uk) *	2004-03-15	2009-03-10	Такеда Фармасьютікал Компані Лімітед	Інгібітори дипептидилпептидази
EP1753730A1 (en)	2004-06-04	2007-02-21	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
WO2006019965A2 (en)	2004-07-16	2006-02-23	Takeda San Diego, Inc.	Dipeptidyl peptidase inhibitors
JP2008507541A (ja) *	2004-07-23	2008-03-13	ロイヤルティ，スーザン・マリー	ペプチダーゼ阻害剤
MX2007002246A (es) *	2004-08-26	2007-04-20	Pfizer Prod Inc	Procedimientos para la preparacion de derivados de isotiazol.
JP2008524331A (ja) *	2004-12-21	2008-07-10	武田薬品工業株式会社	ジペプチジルペプチダーゼ阻害剤
DOP2006000008A (es)	2005-01-10	2006-08-31	Arena Pharm Inc	Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1
GT200600008A (es) *	2005-01-18	2006-08-09		Formulacion de compresion directa y proceso
WO2006081273A1 (en)	2005-01-26	2006-08-03	Allergan, Inc.	3-aryl-3-hydroxy-2-amino-propionic acid amides, 3-heteroayryl-3-hydroxy-2-amino-propionic acid amides and related compounds having analgesic and/or immunostimulant activity
KR20080000665A (ko) *	2005-04-22	2008-01-02	알란토스 파마슈티컬즈 홀딩, 인코포레이티드	디펩티딜 펩티다아제-ⅳ 억제제
AU2006278039B2 (en) *	2005-08-11	2010-10-21	F. Hoffmann-La Roche Ag	Pharmaceutical composition comprising a DPP-lV inhibitor
EP1760076A1 (en)	2005-09-02	2007-03-07	Ferring B.V.	FAP Inhibitors
WO2007033350A1 (en)	2005-09-14	2007-03-22	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors for treating diabetes
PT1931350E (pt) *	2005-09-14	2014-02-12	Takeda Pharmaceutical	Administração de inibidores de dipeptidil peptidase
TW200745080A (en) *	2005-09-16	2007-12-16	Takeda Pharmaceuticals Co	Polymorphs of tartrate salt of 2-[2-(3-(R)-amino-piperidin-1-yl)-5-fluoro-6-oxo-6H-pyrimidin-1-ylmethyl]-benzonitrile and methods of use therefor
EP1924567B1 (en) *	2005-09-16	2012-08-22	Takeda Pharmaceutical Company Limited	Process for the preparation of pyrimidinedione derivatives
TW200745079A (en) *	2005-09-16	2007-12-16	Takeda Pharmaceuticals Co	Polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile and methods of use therefor
GB0526291D0 (en)	2005-12-23	2006-02-01	Prosidion Ltd	Therapeutic method
JP2009531456A (ja) *	2006-03-28	2009-09-03	武田薬品工業株式会社	（ｒ）−３−アミノピペリジン二塩酸塩の調製
WO2007112347A1 (en)	2006-03-28	2007-10-04	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
DK1971862T3 (da)	2006-04-11	2011-02-14	Arena Pharm Inc	Fremgangsmåder til anvendelse af GPR119-receptor til identificering af forbindelser anvendelige til øgning af knoglemasse hos en person
PE20071221A1 (es)	2006-04-11	2007-12-14	Arena Pharm Inc	Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas
BRPI0709984A2 (pt)	2006-04-12	2011-08-02	Probiodrug Ag	inibidores de enzima
US8324383B2 (en)	2006-09-13	2012-12-04	Takeda Pharmaceutical Company Limited	Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
JP5379692B2 (ja)	2006-11-09	2013-12-25	プロビオドルグエージー	潰瘍、癌及び他の疾患の治療のためのグルタミニルシクラーゼの阻害薬としての３−ヒドロキシ−１，５−ジヒドロ−ピロール−２−オン誘導体
TW200838536A (en) *	2006-11-29	2008-10-01	Takeda Pharmaceutical	Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
SI2091948T1 (sl)	2006-11-30	2012-07-31	Probiodrug Ag	Novi inhibitorji glutaminil ciklaze
US8093236B2 (en)	2007-03-13	2012-01-10	Takeda Pharmaceuticals Company Limited	Weekly administration of dipeptidyl peptidase inhibitors
CN101652147B (zh)	2007-04-03	2013-07-24	田边三菱制药株式会社	二肽基肽酶iv抑制化合物和甜味剂的并用
EP2865670B1 (en)	2007-04-18	2017-01-11	Probiodrug AG	Thiourea derivatives as glutaminyl cyclase inhibitors
CL2008003653A1 (es)	2008-01-17	2010-03-05	Mitsubishi Tanabe Pharma Corp	Uso de un inhibidor de sglt derivado de glucopiranosilo y un inhibidor de dppiv seleccionado para tratar la diabetes; y composicion farmaceutica.
EP2146210A1 (en)	2008-04-07	2010-01-20	Arena Pharmaceuticals, Inc.	Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY
CN101823987B (zh) *	2009-03-06	2014-06-04	中国科学院上海药物研究所	一类新的dpp-ⅳ抑制剂及其制备方法和用途
AR077642A1 (es)	2009-07-09	2011-09-14	Arena Pharm Inc	Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo
EP2475428B1 (en)	2009-09-11	2015-07-01	Probiodrug AG	Heterocylcic derivatives as inhibitors of glutaminyl cyclase
WO2011107530A2 (en)	2010-03-03	2011-09-09	Probiodrug Ag	Novel inhibitors
BR112012022478B1 (pt)	2010-03-10	2021-09-21	Probiodrug Ag	Inibidores heterocíclicos de glutaminil ciclase (qc, ec 2.3.2.5), seu processo de preparação, e composição farmacêutica
MX2012011631A (es)	2010-04-06	2013-01-18	Arena Pharm Inc	Moduladores del receptor gpr119 y el tratamiento de trastornos relacionados con el mismo.
JP5945532B2 (ja)	2010-04-21	2016-07-05	プロビオドルグエージー	グルタミニルシクラーゼの阻害剤としてのベンゾイミダゾール誘導体
JP5941916B2 (ja)	2010-09-22	2016-06-29	アリーナファーマシューティカルズ，インコーポレイテッド	Ｇｐｒ１１９レセプターのモジュレーターおよびそれに関連する障害の処置
ES2570167T3 (es)	2011-03-16	2016-05-17	Probiodrug Ag	Derivados de benzimidazol como inhibidores de glutaminil ciclasa
US20140018371A1 (en)	2011-04-01	2014-01-16	Arena Pharmaceuticals, Inc.	Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto
WO2012145361A1 (en)	2011-04-19	2012-10-26	Arena Pharmaceuticals, Inc.	Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2012145604A1 (en)	2011-04-22	2012-10-26	Arena Pharmaceuticals, Inc.	Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2012145603A1 (en)	2011-04-22	2012-10-26	Arena Pharmaceuticals, Inc.	Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2012170702A1 (en)	2011-06-08	2012-12-13	Arena Pharmaceuticals, Inc.	Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2013055910A1 (en)	2011-10-12	2013-04-18	Arena Pharmaceuticals, Inc.	Modulators of the gpr119 receptor and the treatment of disorders related thereto
WO2014074668A1 (en)	2012-11-08	2014-05-15	Arena Pharmaceuticals, Inc.	Modulators of gpr119 and the treatment of disorders related thereto
CN103804362A (zh) *	2012-11-12	2014-05-21	韩文毅	一类治疗糖尿病的化合物及其用途
GB201415598D0 (en)	2014-09-03	2014-10-15	Univ Birmingham	Elavated Itercranial Pressure Treatment
AU2016229982B2 (en)	2015-03-09	2020-06-18	Intekrin Therapeutics, Inc.	Methods for the treatment of nonalcoholic fatty liver disease and/or lipodystrophy
WO2018162722A1 (en)	2017-03-09	2018-09-13	Deutsches Institut Für Ernährungsforschung Potsdam-Rehbrücke	Dpp-4 inhibitors for use in treating bone fractures
JP2020515639A (ja)	2017-04-03	2020-05-28	コヒラス・バイオサイエンシズ・インコーポレイテッド	進行性核上性麻痺の処置のためのＰＰＡＲγアゴニスト
EP3461819B1 (en)	2017-09-29	2020-05-27	Probiodrug AG	Inhibitors of glutaminyl cyclase
IL275333B2 (en)	2017-12-15	2023-09-01	Praxis Biotech LLC	Inhibitors of fibroblast activation protein
TW202239407A (zh)	2020-12-17	2022-10-16	瑞典商阿斯特捷利康公司	Ｎ－（２－（４－氰基四氫噻唑－３－基）－２－側氧基乙基）－喹啉－４－甲醯胺
CN115322129A (zh) *	2022-08-29	2022-11-11	湖北科技学院	双氰基吡咯烷类衍生物及其制备方法和应用

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1990015821A1 (en) *	1989-06-16	1990-12-27	The Upjohn Company	Stabilized, potent grf analogs
US5462928A (en) *	1990-04-14	1995-10-31	New England Medical Center Hospitals, Inc.	Inhibitors of dipeptidyl-aminopeptidase type IV
RU2114119C1 (ru) *	1990-12-13	1998-06-27	Дзе Апджон Компани	Слитой белок и способ выделения слитого белка
WO1998018763A1 (en) *	1996-10-25	1998-05-07	Tanabe Seiyaku Co., Ltd.	Tetrahydroisoquinoline derivatives
TW492957B (en) *	1996-11-07	2002-07-01	Novartis Ag	N-substituted 2-cyanopyrrolidnes
US6011155A (en) *	1996-11-07	2000-01-04	Novartis Ag	N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
ATE380175T1 (de) *	2001-06-27	2007-12-15	Smithkline Beecham Corp	Pyrrolidine als dipeptidyl peptidase inhibitoren
IL158923A0 (en) *	2001-06-27	2004-05-12	Smithkline Beecham Corp	Fluoropyrrolidines as dipeptidyl peptidase inhibitors

2000
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AU784007B2 (en)	2006-01-12
JP2003531204A (ja)	2003-10-21
KR20020093942A (ko)	2002-12-16
PT1280797E (pt)	2005-01-31
MXPA02010490A (es)	2003-03-10
HRP20020813A2 (en)	2004-12-31
ATE279408T1 (de)	2004-10-15
EP1280797B1 (en)	2004-10-13
SI1280797T1 (en)	2005-04-30
IL151917A0 (en)	2003-04-10
ZA200208523B (en)	2003-08-25
WO2001081337A1 (en)	2001-11-01
NO20025118D0 (no)	2002-10-24
DE60106422T2 (de)	2006-02-09
RU2280035C2 (ru)	2006-07-20
EP1280797A1 (en)	2003-02-05
US20040082497A1 (en)	2004-04-29
SK15292002A3 (sk)	2003-04-01
AU5053701A (en)	2001-11-07
DK1280797T3 (da)	2005-01-10
PL357724A1 (en)	2004-07-26
NZ522436A (en)	2003-09-26
GB0010188D0 (en)	2000-06-14
CN1249056C (zh)	2006-04-05
CZ20023512A3 (cs)	2003-03-12
HRP20020813B1 (en)	2006-02-28
CN1426409A (zh)	2003-06-25
HUP0300563A2 (hu)	2003-07-28
ES2231474T3 (es)	2005-05-16
CA2407662A1 (en)	2001-11-01
US7125863B2 (en)	2006-10-24
EE200200603A (et)	2004-04-15
HUP0300563A3 (en)	2006-11-28
NO323750B1 (no)	2007-07-02
NO20025118L (no)	2002-10-24
BR0110021A (pt)	2003-01-21
DE60106422D1 (de)	2004-11-18
HK1051043A1 (en)	2003-07-18

Publication	Publication Date	Title
UA73166C2 (en)	2005-06-15	Dipeptidilpeptidasa iv inhibitor, pharmaceutical composition on its base
AU781245B2 (en)	2005-05-12	Inhibitors of dipeptidyl peptidase IV
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EP1401828B1 (en)	2006-04-12	N-formyl hydroxylamine compounds as inhibitors of pdf
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WO2006098342A1 (en)	2006-09-21	Piperazinyl compounds
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HK1094964A (en)	2007-04-20	Inhibitors of dipeptidyl peptidase iv
HK1064370B (en)	2006-10-20	N-formyl hydroxylamine compounds as inhibitors of pdf