EA020128B1 - Ингибиторы диацилглицеролацилтрансферазы и фармацевтическая композиция, включающая их - Google Patents
Ингибиторы диацилглицеролацилтрансферазы и фармацевтическая композиция, включающая их Download PDFInfo
- Publication number
- EA020128B1 EA020128B1 EA201200868A EA201200868A EA020128B1 EA 020128 B1 EA020128 B1 EA 020128B1 EA 201200868 A EA201200868 A EA 201200868A EA 201200868 A EA201200868 A EA 201200868A EA 020128 B1 EA020128 B1 EA 020128B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- dihydro
- benzazepin
- imidazo
- mmol
- cyclopropyl
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 6
- 102000002148 Diacylglycerol O-acyltransferase Human genes 0.000 title claims abstract 3
- 108010001348 Diacylglycerol O-acyltransferase Proteins 0.000 title claims abstract 3
- 239000003112 inhibitor Substances 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 156
- 150000003839 salts Chemical class 0.000 claims abstract description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 27
- 208000008589 Obesity Diseases 0.000 claims abstract description 9
- 235000020824 obesity Nutrition 0.000 claims abstract description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims abstract description 3
- 239000003937 drug carrier Substances 0.000 claims description 4
- 229910052700 potassium Inorganic materials 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 230000008520 organization Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 192
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 119
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 90
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- -1 [1,3-bis (2,6-diisopropylphenyl) imidazol-2-ylidene] (3-chloropyridyl) Chemical group 0.000 description 41
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- 238000010521 absorption reaction Methods 0.000 description 8
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- 230000000694 effects Effects 0.000 description 8
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- 235000012631 food intake Nutrition 0.000 description 8
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- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- DUVKCXMTUFREIL-UHFFFAOYSA-N 1-[(4-ethoxybenzoyl)amino]cyclopropane-1-carboxylic acid Chemical compound C1=CC(OCC)=CC=C1C(=O)NC1(C(O)=O)CC1 DUVKCXMTUFREIL-UHFFFAOYSA-N 0.000 description 7
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- UMFYXYABQLRNNV-UHFFFAOYSA-N 5,6-dihydro-4h-imidazo[1,2-a][1]benzazepin-4-amine Chemical compound NC1CCC2=CC=CC=C2N2C=CN=C12 UMFYXYABQLRNNV-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
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- OPUJUITUYWGUEP-UHFFFAOYSA-N methyl 1-aminocyclopentane-1-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1(N)CCCC1 OPUJUITUYWGUEP-UHFFFAOYSA-N 0.000 description 1
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- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
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- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
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| US28531709P | 2009-12-10 | 2009-12-10 | |
| PCT/US2010/059158 WO2011071840A1 (en) | 2009-12-10 | 2010-12-07 | Inhibitors of diacylglycerol acyltransferase |
Publications (2)
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| EA201200868A1 EA201200868A1 (ru) | 2012-12-28 |
| EA020128B1 true EA020128B1 (ru) | 2014-08-29 |
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| EA201200868A EA020128B1 (ru) | 2009-12-10 | 2010-12-07 | Ингибиторы диацилглицеролацилтрансферазы и фармацевтическая композиция, включающая их |
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| EP (1) | EP2509981B1 (enExample) |
| JP (1) | JP5631411B2 (enExample) |
| KR (1) | KR101395428B1 (enExample) |
| CN (1) | CN102666543B (enExample) |
| AR (1) | AR079170A1 (enExample) |
| AU (1) | AU2010328410B2 (enExample) |
| BR (1) | BR112012013918A2 (enExample) |
| CA (1) | CA2783684C (enExample) |
| EA (1) | EA020128B1 (enExample) |
| ES (1) | ES2509922T3 (enExample) |
| MX (1) | MX2012006646A (enExample) |
| TW (1) | TWI392680B (enExample) |
| WO (1) | WO2011071840A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9255074B2 (en) | 2010-07-16 | 2016-02-09 | Abbvie Inc. | Process for preparing antiviral compounds |
| BR112013001138A2 (pt) | 2010-07-16 | 2016-07-05 | Abbvie Inc | ligantes de fosfina para reações catalíticas |
| US8975443B2 (en) | 2010-07-16 | 2015-03-10 | Abbvie Inc. | Phosphine ligands for catalytic reactions |
| WO2012009699A2 (en) | 2010-07-16 | 2012-01-19 | Abbott Laboratories | Process for preparing antiviral compounds |
| WO2015120610A1 (en) * | 2014-02-14 | 2015-08-20 | Eli Lilly And Company | Gpr142 agonist compound |
| CN105153195B (zh) * | 2015-09-01 | 2017-09-26 | 汤文建 | 一种三环吡唑[1,5‑d][1,4]苯并氧氮杂卓酮衍生物及其制备方法与用途 |
| BR112021024116A2 (pt) * | 2019-05-31 | 2022-01-11 | Medshine Discovery Inc | Composto bicíclico como inibidor de rip-1 quinase e aplicação do mesmo |
| AR122703A1 (es) * | 2020-07-01 | 2022-09-28 | Rigel Pharmaceuticals Inc | Inhibidores de rip1k |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995014671A1 (en) * | 1993-11-22 | 1995-06-01 | Merck & Co., Inc. | 3-acylaminobenzazepines |
| WO2006020959A2 (en) * | 2004-08-13 | 2006-02-23 | Amgen Inc. | Substituted benzofused heterocycles |
| WO2010056496A1 (en) * | 2008-11-14 | 2010-05-20 | Merck Sharp & Dohme Corp. | Azepinone derivatives |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4847248A (en) | 1986-12-23 | 1989-07-11 | Merck & Co., Inc. | 1,4-Benzodiazepines with 5- and 6-membered heterocyclic rings and their use as cholecystokinins and gastrin antagonists |
| EP0272866A1 (en) | 1986-12-23 | 1988-06-29 | Merck & Co. Inc. | 1,4-Benzodiazepines with 5-membered heterocyclic rings |
| US4735941A (en) | 1986-12-23 | 1988-04-05 | Merck & Co., Inc. | 1,4-benzodiazepines with 5- and 6-membered heterocyclic rings, useful as gastrointestinal and CNS agents |
| IL101850A (en) * | 1991-06-13 | 1996-01-31 | Janssen Pharmaceutica Nv | 11-(4-Piperidinyl)-imidazo (2,1-b) (3) benzazepine derivatives their preparation and pharmaceutical compositions containing them |
| CA2071092A1 (en) | 1991-06-14 | 1992-12-15 | Roger M. Freidinger | 1,4-benzodiazepines with 5-membered heterocyclic rings |
| US5439906A (en) | 1993-11-22 | 1995-08-08 | Merck & Co., Inc. | Antiarrhythmic benzodiazepines |
| JP2840454B2 (ja) | 1993-11-22 | 1998-12-24 | メルク エンド カンパニー インコーポレーテッド | ベンゾジアゼピン類 |
| US5834464A (en) | 1994-11-18 | 1998-11-10 | Merck & Co., Inc. | Imidazolinobenzodiazepines |
| TR199901343T2 (xx) | 1996-12-23 | 1999-09-21 | Elan Pharmaceuticals, Inc. | Sikloalkil, laktam, lakton ve ilgili bile�ikler, bunlar� i�eren farmas�tik bile�imler ve b�yle bile�ikler kullan�larak �-amiloid peptidinin sal�nmas�n� ve/veya sentezini inhibe etmek i�in y�ntemler. |
| GB0012671D0 (en) | 2000-05-24 | 2000-07-19 | Merck Sharp & Dohme | Therapeutic agents |
| KR100910440B1 (ko) * | 2005-05-10 | 2009-08-04 | 에프. 호프만-라 로슈 아게 | 다이아실글리세롤 아실트랜스퍼레이즈 억제제 |
| CA2615463A1 (en) | 2005-07-29 | 2007-02-08 | Merck & Co., Inc. | Heterocyclic benzodiazepine cgrp receptor antagonists |
| US7569590B2 (en) | 2006-09-19 | 2009-08-04 | Bristol-Myers Squibb Company | Use of thianecarboxamides as dgat inhibitors |
| US8394823B2 (en) | 2008-04-11 | 2013-03-12 | Bristol-Myers Squibb Company | Triazolopyridine compounds useful as DGAT1 inhibitors |
| WO2009126624A1 (en) | 2008-04-11 | 2009-10-15 | Bristol-Myers Squibb Company | Triazolo compounds useful as dgat1 inhibitors |
| EP2389366A1 (en) | 2009-01-23 | 2011-11-30 | Msd K.K. | Benzodiazepin-2-on derivatives |
| AU2010216632A1 (en) | 2009-02-17 | 2011-08-04 | Msd K.K. | 1,4-benzodiazepin-2-on derivatives |
-
2010
- 2010-11-30 AR ARP100104417A patent/AR079170A1/es not_active Application Discontinuation
- 2010-12-02 TW TW099141941A patent/TWI392680B/zh not_active IP Right Cessation
- 2010-12-07 JP JP2012543187A patent/JP5631411B2/ja not_active Expired - Fee Related
- 2010-12-07 WO PCT/US2010/059158 patent/WO2011071840A1/en not_active Ceased
- 2010-12-07 KR KR1020127014795A patent/KR101395428B1/ko not_active Expired - Fee Related
- 2010-12-07 AU AU2010328410A patent/AU2010328410B2/en not_active Ceased
- 2010-12-07 MX MX2012006646A patent/MX2012006646A/es unknown
- 2010-12-07 ES ES10799154.9T patent/ES2509922T3/es active Active
- 2010-12-07 EP EP10799154.9A patent/EP2509981B1/en not_active Not-in-force
- 2010-12-07 CN CN201080055334.9A patent/CN102666543B/zh not_active Expired - Fee Related
- 2010-12-07 CA CA2783684A patent/CA2783684C/en not_active Expired - Fee Related
- 2010-12-07 BR BR112012013918A patent/BR112012013918A2/pt not_active IP Right Cessation
- 2010-12-07 EA EA201200868A patent/EA020128B1/ru not_active IP Right Cessation
- 2010-12-07 US US12/961,714 patent/US8299061B2/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995014671A1 (en) * | 1993-11-22 | 1995-06-01 | Merck & Co., Inc. | 3-acylaminobenzazepines |
| WO2006020959A2 (en) * | 2004-08-13 | 2006-02-23 | Amgen Inc. | Substituted benzofused heterocycles |
| WO2010056496A1 (en) * | 2008-11-14 | 2010-05-20 | Merck Sharp & Dohme Corp. | Azepinone derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102666543A (zh) | 2012-09-12 |
| EA201200868A1 (ru) | 2012-12-28 |
| BR112012013918A2 (pt) | 2016-04-26 |
| JP5631411B2 (ja) | 2014-11-26 |
| AU2010328410A1 (en) | 2012-07-26 |
| AU2010328410B2 (en) | 2014-02-06 |
| TWI392680B (zh) | 2013-04-11 |
| US8299061B2 (en) | 2012-10-30 |
| MX2012006646A (es) | 2012-06-25 |
| WO2011071840A1 (en) | 2011-06-16 |
| ES2509922T3 (es) | 2014-10-20 |
| CN102666543B (zh) | 2014-12-24 |
| CA2783684A1 (en) | 2011-06-16 |
| EP2509981B1 (en) | 2014-08-06 |
| EP2509981A1 (en) | 2012-10-17 |
| TW201130844A (en) | 2011-09-16 |
| US20110144091A1 (en) | 2011-06-16 |
| KR20120099457A (ko) | 2012-09-10 |
| CA2783684C (en) | 2014-02-25 |
| AR079170A1 (es) | 2011-12-28 |
| KR101395428B1 (ko) | 2014-05-14 |
| JP2013513607A (ja) | 2013-04-22 |
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