UA75647C2 - Mercaptoacetylamide derivatives, a process for their preparation, pharmaceutical composition based thereon and a process for preparation of intermediate compound - Google Patents
Mercaptoacetylamide derivatives, a process for their preparation, pharmaceutical composition based thereon and a process for preparation of intermediate compound Download PDFInfo
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- UA75647C2 UA75647C2 UA20031110184A UA20031110184A UA75647C2 UA 75647 C2 UA75647 C2 UA 75647C2 UA 20031110184 A UA20031110184 A UA 20031110184A UA 20031110184 A UA20031110184 A UA 20031110184A UA 75647 C2 UA75647 C2 UA 75647C2
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- aryl
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- 238000000034 method Methods 0.000 title claims abstract description 31
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- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US28330501P | 2001-04-12 | 2001-04-12 | |
PCT/EP2002/003668 WO2002083671A1 (en) | 2001-04-12 | 2002-04-03 | Mercaptoacetylamide derivatives, a process for their preparation and their use |
Publications (1)
Publication Number | Publication Date |
---|---|
UA75647C2 true UA75647C2 (en) | 2006-05-15 |
Family
ID=23085405
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
UA20031110184A UA75647C2 (en) | 2001-04-12 | 2002-03-04 | Mercaptoacetylamide derivatives, a process for their preparation, pharmaceutical composition based thereon and a process for preparation of intermediate compound |
Country Status (17)
Country | Link |
---|---|
US (1) | US6602866B2 (zh) |
KR (1) | KR100910929B1 (zh) |
AR (1) | AR034307A1 (zh) |
CR (1) | CR7074A (zh) |
DK (1) | DK1381605T3 (zh) |
EC (1) | ECSP034782A (zh) |
GB (1) | GB0119305D0 (zh) |
GT (1) | GT200200069A (zh) |
IL (1) | IL158289A (zh) |
MY (1) | MY128226A (zh) |
PE (1) | PE20021079A1 (zh) |
RS (1) | RS50919B (zh) |
TN (1) | TNSN03083A1 (zh) |
TW (1) | TWI319764B (zh) |
UA (1) | UA75647C2 (zh) |
UY (1) | UY27255A1 (zh) |
ZA (1) | ZA200307096B (zh) |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1481960A4 (en) * | 2002-02-04 | 2005-04-06 | Kaneka Corp | PROCESS FOR OBTAINING OPTICALLY ACTIVE 2-HALOGENO-CARBOXYLIC ACIDS |
TW200838501A (en) | 2007-02-02 | 2008-10-01 | Theravance Inc | Dual-acting antihypertensive agents |
TWI448284B (zh) * | 2007-04-24 | 2014-08-11 | Theravance Inc | 雙效抗高血壓劑 |
TWI406850B (zh) * | 2007-06-05 | 2013-09-01 | Theravance Inc | 雙效苯并咪唑抗高血壓劑 |
US7834041B2 (en) * | 2007-09-07 | 2010-11-16 | Theravance, Inc. | Dual-acting antihypertensive agents |
EP2234608A2 (en) | 2007-12-11 | 2010-10-06 | Viamet Pharmaceuticals, Inc. | Metalloenzyme inhibitors using metal binding moieties in combination with targeting moieties |
CA2705921A1 (en) | 2007-12-11 | 2009-06-18 | Theravance, Inc. | Dual-acting benzoimidazole derivatives and their use as antihypertensive agents |
EP2297113A1 (en) | 2008-04-29 | 2011-03-23 | Theravance, Inc. | Dual-acting antihypertensive agents |
US7863309B2 (en) | 2008-07-24 | 2011-01-04 | Theravance, Inc. | Dual-acting antihypertensive agents |
WO2011005674A1 (en) | 2009-07-07 | 2011-01-13 | Theravance, Inc. | Dual-acting pyrazole antihypertensive agents |
JP2012533626A (ja) | 2009-07-22 | 2012-12-27 | セラヴァンス, インコーポレーテッド | 二重作用オキサゾール降圧剤 |
EP2526095A1 (en) | 2010-01-19 | 2012-11-28 | Theravance, Inc. | Dual-acting thiophene, pyrrole, thiazole and furan antihypertensive agents |
EP2651900B1 (en) | 2010-12-15 | 2015-08-19 | Theravance Biopharma R&D IP, LLC | Neprilysin inhibitors |
CA2817368C (en) | 2010-12-15 | 2019-12-31 | Theravance, Inc. | Neprilysin inhibitors |
US8449890B2 (en) | 2011-02-17 | 2013-05-28 | Theravance, Inc. | Neprilysin inhibitors |
EP2675795B1 (en) | 2011-02-17 | 2016-04-20 | Theravance Biopharma R&D IP, LLC | Substituted aminobutyric derivatives as neprilysin inhibitors |
EP2714648B1 (en) | 2011-05-31 | 2017-08-16 | Theravance Biopharma R&D IP, LLC | Neprilysin inhibitors |
JP5959075B2 (ja) | 2011-05-31 | 2016-08-02 | セラヴァンス バイオファーマ アール&ディー アイピー, エルエルシー | ネプリライシン阻害剤 |
EP2714662B1 (en) | 2011-05-31 | 2017-10-11 | Theravance Biopharma R&D IP, LLC | Neprilysin inhibitors |
TWI560172B (en) | 2011-11-02 | 2016-12-01 | Theravance Biopharma R&D Ip Llc | Neprilysin inhibitors |
WO2013181332A1 (en) | 2012-05-31 | 2013-12-05 | Theravance, Inc. | Nitric oxide donor neprilysin inhibitors |
WO2013184898A1 (en) | 2012-06-08 | 2013-12-12 | Theravance, Inc. | Neprilysin inhibitors |
AU2013271537B2 (en) | 2012-06-08 | 2017-05-11 | Theravance Biopharma R&D Ip, Llc | Neprilysin inhibitors |
JP6092390B2 (ja) | 2012-08-08 | 2017-03-08 | セラヴァンス バイオファーマ アール&ディー アイピー, エルエルシー | ネプリライシン阻害剤 |
HUE034210T2 (hu) | 2013-03-05 | 2018-02-28 | Theravance Biopharma R&D Ip Llc | Neprilizininhibitorok |
US9585882B2 (en) | 2014-01-30 | 2017-03-07 | Theravance Biopharma R&D Ip, Llc | Neprilysin inhibitors |
SG11201605965UA (en) | 2014-01-30 | 2016-08-30 | Theravance Biopharma R&D Ip Llc | Neprilysin inhibitors |
KR102640906B1 (ko) | 2015-02-11 | 2024-02-27 | 세라밴스 바이오파마 알앤디 아이피, 엘엘씨 | 네프릴리신 저해제로서 (2s,4r)-5-(5''-클로로-2''-플루오로비페닐-4-일)-4-(에톡시옥살릴아미노)-2-히드록시메틸-2-메틸펜타노익산 |
EP3259255B1 (en) | 2015-02-19 | 2020-10-21 | Theravance Biopharma R&D IP, LLC | (2r,4r)-5-(5'-chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-[(5-methyloxazole-2-carbonyl)amino]pentanoic acid |
MX2018010727A (es) | 2016-03-08 | 2019-01-24 | Theravance Biopharma R&D Ip Llc | Acido (2s,4r)-5-(5'-cloro-2'-fluoro-[1,1'-bifenil]-4-il)-2-(etoxim etil)-4-(3-hidroxiisoxazol-5-carboxamido)-2-metilpentanoico cristalino, y sus usos. |
Family Cites Families (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3334095A (en) | 1965-02-16 | 1967-08-01 | Sandoz Ag | Novel pyrrolo-oxazines and pyrrolo-oxazoles |
US3334091A (en) | 1965-03-25 | 1967-08-01 | Sandoz Ag | Sedatives |
GB1525845A (en) | 1976-07-30 | 1978-09-20 | Ucb Sa | 1,2,4,5-tetrahydro-3h-2-benzazepin-3-ones |
IE50839B1 (en) | 1980-02-26 | 1986-07-23 | Wyeth John & Brother Ltd | Novel processes for preparing proline derivatives and analogous compounds |
EP0042100A1 (de) | 1980-06-13 | 1981-12-23 | F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft | Pyrazolopyridazin-Derivate, Zwischenprodukte und Verfahren zu deren Herstellung, sowie diese enthaltende Arzneimittel |
US4320057A (en) | 1980-06-23 | 1982-03-16 | American Home Products Corporation | Aryl--pyrrolo--thiazepin--diones and aryl--piperidino--thiazepin--diones |
US4415496A (en) | 1981-03-23 | 1983-11-15 | Merck & Co., Inc. | Bicyclic lactams |
GB2128984B (en) | 1982-05-12 | 1985-05-22 | Hoffmann La Roche | Diaza-bicyclic compounds |
NZ204130A (en) | 1982-05-12 | 1986-03-14 | Hoffmann La Roche | Bicyclic heterocyclic compounds and pharmaceutical compositions |
US4552889A (en) | 1983-06-09 | 1985-11-12 | Eli Lilly And Company | 3-Mercaptomethyl-2-oxo-1-pyrrolidine acetic acids and use for hypertension |
US4692438A (en) | 1984-08-24 | 1987-09-08 | Hoffmann-La Roche Inc. | Pyridazo-diazepines, diazocines, and -triazepines having anti-hypertensive activity |
US4584294A (en) | 1984-11-07 | 1986-04-22 | Merck & Co., Inc. | Fused tricyclic lactams as angiotensin converting enzyme inhibitors and as antihypertensive agents |
ZA863170B (en) | 1985-04-30 | 1987-12-30 | Lilly Co Eli | 7-substituted bicyclic pyrazolidinones |
US4973585A (en) | 1986-06-13 | 1990-11-27 | Merrell Dow Pharmaceuticals | Tricyclic lactams active as antihypertensive agents |
ZA874106B (en) | 1986-06-13 | 1987-12-08 | Merrell Dow Pharmaceuticals Inc. | Novel antihypertensive agent |
ZA874107B (zh) | 1986-06-13 | 1987-12-09 | ||
GB8629875D0 (en) | 1986-12-15 | 1987-01-28 | Hoffmann La Roche | Pyridazodiazepine derivatives |
US4824832A (en) | 1987-12-30 | 1989-04-25 | Merrell Dow Pharmaceuticals Inc. | Sulfhydryl containing tricyclic lactams and their pharmacological methods of use |
GB8926512D0 (en) | 1989-11-23 | 1990-01-10 | Pfizer Ltd | Therapeutic agents |
AU7168091A (en) | 1989-12-22 | 1991-07-24 | Schering Corporation | Mercaptocycloacyl aminoacid endopeptidase inhibitors |
US5430145A (en) * | 1990-10-18 | 1995-07-04 | Merrell Dow Pharmaceuticals Inc. | Mercaptoacetylamide derivatives useful as inhibitors of enkephalinase and ace |
CA2053340C (en) | 1990-10-18 | 2002-04-02 | Timothy P. Burkholder | Mercaptoacetylamide derivatives useful as inhibitors of enkephalinase and ace |
US5491143A (en) | 1990-10-18 | 1996-02-13 | Merrell Dow Pharmaceuticals Inc. | Mercaptoacetylamide derivatives useful as inhibitors of enkephalinase and ACE |
DK0492369T3 (da) | 1990-12-21 | 1997-10-13 | Merrell Pharma Inc | Hidtil ukendte tricycliske amino- og nitro-forbindelser med ACE-hæmmende virkning |
US5208230A (en) | 1990-12-21 | 1993-05-04 | Merrell Dow Pharmaceuticals | Amino and nitro containing tricyclic compounds useful as inhibitors of ACE |
FR2679564A1 (fr) | 1991-07-23 | 1993-01-29 | Inst Nat Sante Rech Med | Nouveaux acylmercaptoalcanoldipeptides, leur preparation et les compositions qui les contiennent. |
EP0605589A1 (en) | 1991-09-16 | 1994-07-13 | Schering Corporation | Pharmaceutical compositions comprising natriuretic peptides or neutral endopeptidase inhibitors for treating or preventing myointimal proliferation |
DK0534363T3 (da) | 1991-09-27 | 1997-09-22 | Merrell Pharma Inc | 2-substituerede indan-2-mercaptoacetylamid-forbindelse med inhiberende virkning på enkephalinase og ACE. |
AU657793B2 (en) | 1991-09-27 | 1995-03-23 | Merrell Pharmaceuticals Inc. | Novel 2-substituted indane-2-carboxyalkyl derivatives useful as inhibitors of enkephalinase and ACE |
AU668707B2 (en) | 1992-02-14 | 1996-05-16 | Merrell Pharmaceuticals Inc. | Aminoacetylmercaptoacetylamide derivatives useful as inhibitors of enkephalinase and ACE |
WO1993023403A1 (en) | 1992-05-15 | 1993-11-25 | Merrell Dow Pharmaceuticals Inc. | NOVEL MERCAPTOACETYLAMIDO PYRIDAZO[1,2]PYRIDAZINE, PYRAZOLO[1,2]PYRIDAZINE, PYRIDAZO[1,2-a][1,2]DIAZEPINE AND PYRAZOLO[1,2-a][1,2]DIAZEPINE DERIVATIVES USEFUL AS INHIBITORS OF ENKEPHALINASE AND ACE |
RU2124503C1 (ru) | 1992-05-18 | 1999-01-10 | И.Р.Сквибб энд Санз, Инк. | Гетероциклические азотсодержащие производные карбоновой кислоты, способ их получения и фармацевтическая композиция |
US5238932A (en) | 1992-05-20 | 1993-08-24 | Merrell Dow Pharmaceuticals Inc. | Mercaptoacetylamide tricyclic derivatives useful as inhibitors of enkephalinase |
US5679671A (en) * | 1993-06-11 | 1997-10-21 | Eisai Co., Ltd. | Amino acid derivative |
US5525723A (en) | 1993-11-18 | 1996-06-11 | Bristol-Myers Squibb Co. | Compounds containing a fused multiple ring lactam |
DE69416873T2 (de) * | 1994-02-14 | 1999-07-29 | Merrell Pharmaceuticals Inc., Cincinnati, Ohio | Mercaptoacetylamid disulfidderivate als enkephalinase und ace inhibitoren |
DK0751774T3 (da) * | 1994-03-24 | 2003-12-08 | Merrell Pharma Inc | Hypocholesterolæmiske mercaptoacetylamiddisulfid-derivater |
-
2001
- 2001-08-08 GB GBGB0119305.1A patent/GB0119305D0/en not_active Ceased
-
2002
- 2002-03-04 UA UA20031110184A patent/UA75647C2/uk unknown
- 2002-04-03 RS YUP-787/03A patent/RS50919B/sr unknown
- 2002-04-03 DK DK02732549T patent/DK1381605T3/da active
- 2002-04-03 KR KR1020037013181A patent/KR100910929B1/ko not_active IP Right Cessation
- 2002-04-08 US US10/118,179 patent/US6602866B2/en not_active Expired - Lifetime
- 2002-04-10 TW TW091107133A patent/TWI319764B/zh not_active IP Right Cessation
- 2002-04-10 UY UY27255A patent/UY27255A1/es not_active Application Discontinuation
- 2002-04-10 PE PE2002000294A patent/PE20021079A1/es not_active Application Discontinuation
- 2002-04-10 GT GT200200069A patent/GT200200069A/es unknown
- 2002-04-10 AR ARP020101321A patent/AR034307A1/es active IP Right Grant
- 2002-04-10 MY MYPI20021326A patent/MY128226A/en unknown
-
2003
- 2003-07-08 TN TNPCT/EP2002/003668A patent/TNSN03083A1/en unknown
- 2003-09-11 ZA ZA200307096A patent/ZA200307096B/en unknown
- 2003-09-12 CR CR7074A patent/CR7074A/es not_active Application Discontinuation
- 2003-09-26 EC EC2003004782A patent/ECSP034782A/es unknown
- 2003-10-07 IL IL158289A patent/IL158289A/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
MY128226A (en) | 2007-01-31 |
GB0119305D0 (en) | 2001-10-03 |
RS50919B (sr) | 2010-08-31 |
KR20040008153A (ko) | 2004-01-28 |
TWI319764B (en) | 2010-01-21 |
US20020193589A1 (en) | 2002-12-19 |
DK1381605T3 (da) | 2005-05-09 |
AR034307A1 (es) | 2004-02-18 |
UY27255A1 (es) | 2002-07-31 |
TNSN03083A1 (en) | 2005-12-23 |
IL158289A (en) | 2010-11-30 |
GT200200069A (es) | 2002-12-17 |
US6602866B2 (en) | 2003-08-05 |
KR100910929B1 (ko) | 2009-08-06 |
YU78703A (sh) | 2006-05-25 |
ECSP034782A (es) | 2003-12-01 |
PE20021079A1 (es) | 2003-02-19 |
CR7074A (es) | 2007-12-04 |
ZA200307096B (en) | 2004-09-06 |
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