ZA200500026B - 7,8,9,10-tetrahydro-6H-azepino, 6,7,8,9-tetrahydo-pyrido and 2,3-dihydro-2H-pyrroloÄ2,1-bÜ-quinazolinone derivatives. - Google Patents
7,8,9,10-tetrahydro-6H-azepino, 6,7,8,9-tetrahydo-pyrido and 2,3-dihydro-2H-pyrroloÄ2,1-bÜ-quinazolinone derivatives. Download PDFInfo
- Publication number
- ZA200500026B ZA200500026B ZA200500026A ZA200500026A ZA200500026B ZA 200500026 B ZA200500026 B ZA 200500026B ZA 200500026 A ZA200500026 A ZA 200500026A ZA 200500026 A ZA200500026 A ZA 200500026A ZA 200500026 B ZA200500026 B ZA 200500026B
- Authority
- ZA
- South Africa
- Prior art keywords
- phenyl
- ethyl
- quinazolin
- tetrahydro
- urea
- Prior art date
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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
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP0207608 | 2002-07-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200500026B true ZA200500026B (en) | 2005-10-20 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200500026A ZA200500026B (en) | 2002-07-09 | 2005-01-03 | 7,8,9,10-tetrahydro-6H-azepino, 6,7,8,9-tetrahydo-pyrido and 2,3-dihydro-2H-pyrroloÄ2,1-bÜ-quinazolinone derivatives. |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US7067519B2 (ja) |
| EP (1) | EP1521583B1 (ja) |
| JP (1) | JP4498922B2 (ja) |
| CN (1) | CN1556705B (ja) |
| AU (1) | AU2003246657A1 (ja) |
| CA (1) | CA2460051A1 (ja) |
| DE (1) | DE60311101T2 (ja) |
| ES (1) | ES2278197T3 (ja) |
| IL (1) | IL166100A0 (ja) |
| MX (1) | MXPA04002269A (ja) |
| NO (1) | NO20050668L (ja) |
| NZ (1) | NZ538029A (ja) |
| PL (1) | PL373223A1 (ja) |
| RU (1) | RU2005103398A (ja) |
| WO (1) | WO2004004733A1 (ja) |
| ZA (1) | ZA200500026B (ja) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1780820A (zh) * | 2003-04-28 | 2006-05-31 | 埃科特莱茵药品有限公司 | 作为阿立新受体拮抗剂的喹喔啉－3－酮衍生物 |
| EP1607069B1 (fr) * | 2004-06-15 | 2009-12-23 | Tornier | Prothese totale d'epaule de type inverse |
| EP2049110B1 (en) | 2006-07-14 | 2014-08-20 | Merck Sharp & Dohme Corp. | Bridged diazepan orexin receptor antagonists |
| ATE458740T1 (de) * | 2006-08-28 | 2010-03-15 | Actelion Pharmaceuticals Ltd | 1,4,5,6,7,8-hexahydro-1,2,5-triaza-azulen- derivate als orexinrezeptor-antagonisten |
| PE20081229A1 (es) | 2006-12-01 | 2008-08-28 | Merck & Co Inc | Antagonistas de receptor de orexina de diazepam sustituido |
| AU2007337659A1 (en) | 2006-12-22 | 2008-07-03 | Actelion Pharmaceuticals Ltd. | 5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine derivatives |
| AU2008255005B2 (en) | 2007-05-18 | 2013-05-02 | Merck Sharp & Dohme Corp. | OXO bridged diazepan orexin receptor antagonists |
| JP2010528007A (ja) | 2007-05-23 | 2010-08-19 | メルク・シャープ・エンド・ドーム・コーポレイション | シクロプロピルピロリジンオレキシン受容体アンタゴニスト |
| PL2152690T3 (pl) | 2007-05-23 | 2012-06-29 | Merck Sharp & Dohme | Pirydylo piperydynowi antagoniści receptora oreksyny |
| EP2161266A1 (en) | 2008-08-22 | 2010-03-10 | EVOTEC Neurosciences GmbH | Benzofuran derivatives as orexin receptor antagonists |
| CA2741125A1 (en) | 2008-10-22 | 2010-04-29 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| CN102271509A (zh) | 2008-10-31 | 2011-12-07 | 默沙东公司 | 用于抗糖尿病药的新型环苯并咪唑衍生物 |
| JP5847087B2 (ja) | 2009-10-23 | 2016-01-20 | ヤンセン ファーマシューティカ エヌ．ベー． | オレキシン受容体調節因子としての縮合複素環式化合物 |
| DK2491038T3 (da) * | 2009-10-23 | 2016-07-18 | Janssen Pharmaceutica Nv | Disubstituerede octahydropyrrolo [3,4-c]pyrroler som orexin receptormodulatorer |
| WO2011050202A1 (en) | 2009-10-23 | 2011-04-28 | Janssen Pharmaceutica Nv | Fused heterocyclic compounds as orexin receptor modulators |
| US8895596B2 (en) | 2010-02-25 | 2014-11-25 | Merck Sharp & Dohme Corp | Cyclic benzimidazole derivatives useful as anti-diabetic agents |
| WO2011138265A2 (en) | 2010-05-03 | 2011-11-10 | Evotec Ag | Indole and indazole derivatives as orexin receptor antagonists |
| WO2011138266A1 (en) | 2010-05-03 | 2011-11-10 | Evotec Ag | Indolizine and imidazopyridine derivatives as orexin receptor antagonists |
| EP2677869B1 (en) | 2011-02-25 | 2017-11-08 | Merck Sharp & Dohme Corp. | Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agents |
| WO2012145581A1 (en) | 2011-04-20 | 2012-10-26 | Janssen Pharmaceutica Nv | Disubstituted octahy-dropyrrolo [3,4-c] pyrroles as orexin receptor modulators |
| KR20140036312A (ko) * | 2011-07-13 | 2014-03-25 | 산텐 세이야꾸 가부시키가이샤 | Ｐａｒｐ 저해 활성을 갖는 신규 화합물 |
| AR088352A1 (es) | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
| SG11201404738QA (en) | 2012-02-07 | 2014-10-30 | Eolas Therapeutics Inc | Substituted prolines / piperidines as orexin receptor antagonists |
| US9440982B2 (en) | 2012-02-07 | 2016-09-13 | Eolas Therapeutics, Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| CA2880901A1 (en) | 2012-08-02 | 2014-02-06 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| WO2014130608A1 (en) | 2013-02-22 | 2014-08-28 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
| EP2970119B1 (en) | 2013-03-14 | 2021-11-03 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| EP3180332B1 (en) | 2014-08-13 | 2021-10-27 | Eolas Therapeutics Inc. | Difluoropyrrolidines as orexin receptor modulators |
| CN109219606B (zh) | 2016-02-12 | 2021-10-01 | 阿斯利康(瑞典)有限公司 | 食欲素受体调节剂的卤素取代的哌啶 |
| CA3016706A1 (en) | 2016-03-10 | 2017-09-14 | Janssen Pharmaceutica Nv | Methods of treating depression using orexin-2 receptor antagonists |
| WO2017194548A1 (en) | 2016-05-10 | 2017-11-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of autoimmune inflammatory diseases |
| EP3551176A4 (en) | 2016-12-06 | 2020-06-24 | Merck Sharp & Dohme Corp. | ANTIDIABETIC HETEROCYCLIC COMPOUNDS |
| WO2018118670A1 (en) | 2016-12-20 | 2018-06-28 | Merck Sharp & Dohme Corp. | Antidiabetic spirochroman compounds |
| CA3069745A1 (en) * | 2017-08-03 | 2019-02-07 | Galectin Sciences, Llc | Compounds for the prevention and treatment of medical disorders and uses thereof |
| EP3895707B1 (en) * | 2018-12-12 | 2023-10-04 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU173438B (hu) * | 1975-11-27 | 1979-05-28 | Chinoin Gyogyszer Es Vegyeszet | Sposob poluchenija novykh proizvodnykh 4-okso-1,6,7,8-/tetragidro-4h-pirido/1,2/pirimidina s zaderzhivajuhhejj vozgoranie aktivnot'ju i protivosvertivajuhhem effektom |
| HU191192B (en) * | 1982-11-16 | 1987-01-28 | Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt,Hu | Process for producing new azepino /1,2-a/ pyrimidine derivatives of bronchodilating activity and acid additional salts thereof and pharmaceiutical compositions containing them |
| US4678499A (en) * | 1985-03-11 | 1987-07-07 | E. I. Du Pont De Nemours And Company | Herbicidal sulfonamides |
| US5753664A (en) * | 1995-03-16 | 1998-05-19 | Takeda Chemical Industries, Ltd. | Heterocyclic compounds, their production and use |
| US6057315A (en) * | 1996-12-09 | 2000-05-02 | Warner-Lambertt Company | Antibacterial agents |
| AR016817A1 (es) | 1997-08-14 | 2001-08-01 | Smithkline Beecham Plc | Derivados de fenilurea o feniltiourea, procedimiento para su preparacion, coleccion de compuestos, compuestos intermediarios, composicion farmaceutica,metodo de tratamiento y uso de dichos compuestos para la manufactura de un medicamento |
| ES2196806T3 (es) | 1998-05-08 | 2003-12-16 | Smithkline Beecham Plc | Derivados de fenilurea y de feniltiourea. |
| JP2002536445A (ja) | 1999-02-12 | 2002-10-29 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | オレキシン受容体アンタゴニストとしてのフェニル尿素およびフェニルチオ尿素誘導体 |
| WO2000047576A1 (en) | 1999-02-12 | 2000-08-17 | Smithkline Beecham Plc | Cinnamide derivatives as orexin-1 receptors antagonists |
| JP2002536447A (ja) | 1999-02-12 | 2002-10-29 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | フェニル尿素およびフェニルチオ尿素誘導体 |
| DE19906975B4 (de) * | 1999-02-19 | 2004-04-15 | Lts Lohmann Therapie-Systeme Ag | Arzneiform zur Behandlung von Alzheimer'scher Demenz |
| AU2001235804A1 (en) * | 2000-03-06 | 2001-09-17 | Astrazeneca Ab | Therapy |
| CA2408343A1 (en) | 2000-05-11 | 2002-11-07 | Banyu Pharmaceutical Co., Ltd. | N-acyltetrahydroisoquinoline derivatives |
| PT1289955E (pt) | 2000-06-16 | 2005-08-31 | Smithkline Beecham Plc | Piperidinas para utilizacao como antagonistas dos receptores da orexina |
| EP1353918B1 (en) | 2000-11-28 | 2005-01-12 | Smithkline Beecham Plc | Morpholine derivatives as antagonists of orexin receptors |
| GB0121214D0 (en) * | 2001-08-31 | 2001-10-24 | Btg Int Ltd | Synthetic method |
| WO2003032989A1 (en) * | 2001-10-18 | 2003-04-24 | Boehringer Ingelheim Pharmaceuticals, Inc. | 1,4-disubstituted benzo-fused urea compounds as cytokine inhibitors |
| US6676976B2 (en) * | 2002-03-21 | 2004-01-13 | Council Of Scientific And Industrial Research | Process for the production of vasicine |
-
2003
- 2003-07-08 WO PCT/EP2003/007297 patent/WO2004004733A1/en active IP Right Grant
- 2003-07-08 JP JP2004518740A patent/JP4498922B2/ja not_active Expired - Fee Related
- 2003-07-08 EP EP03762653A patent/EP1521583B1/en not_active Expired - Lifetime
- 2003-07-08 ES ES03762653T patent/ES2278197T3/es not_active Expired - Lifetime
- 2003-07-08 CA CA002460051A patent/CA2460051A1/en not_active Abandoned
- 2003-07-08 DE DE60311101T patent/DE60311101T2/de not_active Expired - Lifetime
- 2003-07-08 MX MXPA04002269A patent/MXPA04002269A/es unknown
- 2003-07-08 AU AU2003246657A patent/AU2003246657A1/en not_active Abandoned
- 2003-07-08 NZ NZ538029A patent/NZ538029A/en unknown
- 2003-07-08 CN CN038011042A patent/CN1556705B/zh not_active Expired - Fee Related
- 2003-07-08 RU RU2005103398/04A patent/RU2005103398A/ru not_active Application Discontinuation
- 2003-07-08 PL PL03373223A patent/PL373223A1/xx not_active Application Discontinuation
- 2003-07-08 US US10/489,350 patent/US7067519B2/en not_active Expired - Fee Related
-
2005
- 2005-01-03 IL IL16610005A patent/IL166100A0/xx unknown
- 2005-01-03 ZA ZA200500026A patent/ZA200500026B/en unknown
- 2005-02-08 NO NO20050668A patent/NO20050668L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2460051A1 (en) | 2004-01-15 |
| WO2004004733A1 (en) | 2004-01-15 |
| IL166100A0 (en) | 2006-01-15 |
| NO20050668L (no) | 2005-04-05 |
| CN1556705B (zh) | 2010-04-28 |
| JP4498922B2 (ja) | 2010-07-07 |
| RU2005103398A (ru) | 2006-06-27 |
| NZ538029A (en) | 2006-08-31 |
| US7067519B2 (en) | 2006-06-27 |
| EP1521583B1 (en) | 2007-01-10 |
| PL373223A1 (en) | 2005-08-22 |
| US20050009852A1 (en) | 2005-01-13 |
| AU2003246657A1 (en) | 2004-01-23 |
| EP1521583A1 (en) | 2005-04-13 |
| DE60311101D1 (de) | 2007-02-22 |
| JP2005532381A (ja) | 2005-10-27 |
| DE60311101T2 (de) | 2007-06-21 |
| ES2278197T3 (es) | 2007-08-01 |
| CN1556705A (zh) | 2004-12-22 |
| MXPA04002269A (es) | 2004-06-29 |
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