DE60108420T2 - Morpholinderivate als antagonisten an orexinrezeptoren - Google Patents
Morpholinderivate als antagonisten an orexinrezeptoren Download PDFInfo
- Publication number
- DE60108420T2 DE60108420T2 DE60108420T DE60108420T DE60108420T2 DE 60108420 T2 DE60108420 T2 DE 60108420T2 DE 60108420 T DE60108420 T DE 60108420T DE 60108420 T DE60108420 T DE 60108420T DE 60108420 T2 DE60108420 T2 DE 60108420T2
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- alkyl
- radical
- optionally substituted
- phenyl
- alkoxy
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| GB0114291A GB0114291D0 (en) | 2001-06-12 | 2001-06-12 | Compounds |
| PCT/EP2001/013687 WO2002044172A1 (en) | 2000-11-28 | 2001-11-22 | Morpholine derivatives as antagonists of orexin receptors |
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Families Citing this family (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4309135B2 (ja) | 2001-05-05 | 2009-08-05 | スミスクライン ビーチャム ピー エル シー | Ｎ−アロイルサイクリックアミン |
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| GB0130335D0 (en) * | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
| RU2005103398A (ru) | 2002-07-09 | 2006-06-27 | Актелион Фармасьютикалз Лтд. (Ch) | Производные 7,8,9,10-тетрагидро-6h-азепино-, 6,7,8,9-тетрагидропиридо-и 2,3-дигидро-2h-пирроло-[2,1-b]-хиназолинона |
| WO2004026866A1 (en) * | 2002-09-18 | 2004-04-01 | Glaxo Group Limited | N-aroyl cyclic amines as orexin receptor antagonists |
| AU2003294671A1 (en) * | 2002-10-11 | 2004-05-04 | Actelion Pharmaceuticals Ltd. | Sulfonylamino-acetic derivatives and their use as orexin receptor antagonists |
| GB0225938D0 (en) * | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| GB0225944D0 (en) * | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| CA2520839A1 (en) | 2003-04-28 | 2004-11-11 | Actelion Pharmaceuticals Ltd | Quinoxalinone-3- one derivatives as orexin receptor antagonists |
| HRP20150371T1 (hr) | 2004-03-01 | 2015-05-08 | Actelion Pharmaceuticals Ltd. | Supstituirani derivati 1,2,3,4-tetrahidroizokinolina |
| EP2305352A1 (en) | 2004-04-02 | 2011-04-06 | Merck Sharp & Dohme Corp. | 5-alpha-reductase inhibitors for use in the treatment of men with metabolic and anthropometric disorders |
| US20060178307A1 (en) * | 2005-01-26 | 2006-08-10 | The Regents Of The University Of California | Modulation of NMDA receptor currents via orexin receptor and/or CRF receptor |
| US7501395B2 (en) | 2005-04-25 | 2009-03-10 | Eisai R & D Management Co., Ltd. | Method of screening for antianxiety drugs |
| WO2006126074A2 (en) * | 2005-05-26 | 2006-11-30 | Orchid Research Laboratories Limited | Heterocyclic derivatives |
| WO2007136790A2 (en) * | 2006-05-18 | 2007-11-29 | Mannkind Corporation | Intracellular kinase inhibitors |
| US8618102B2 (en) | 2006-07-14 | 2013-12-31 | Merck Sharp & Dohme Corp. | Bridged diazepan orexin receptor antagonists |
| EP2079690B1 (en) * | 2006-09-29 | 2010-09-15 | Actelion Pharmaceuticals Ltd. | 3-aza-bicyclo[3.1.0]hexane derivatives |
| PE20081229A1 (es) | 2006-12-01 | 2008-08-28 | Merck & Co Inc | Antagonistas de receptor de orexina de diazepam sustituido |
| WO2008065626A2 (en) | 2006-12-01 | 2008-06-05 | Actelion Pharmaceuticals Ltd | 3-heteroaryl (amino or amido)-1- (biphenyl or phenylthiazolyl) carbonylpiperidine derivativesas orexin receptor inhibitors |
| CL2007003827A1 (es) | 2006-12-28 | 2008-09-26 | Actelion Pharmaceuticals Ltd | Compuestos derivados de n-(2-aza-biciclo(3.1.0)hex-3-ilmetil)amida; y su uso para prevenir o tratar la depresion, neurosis, esquizofrenia, ansiedad, adicciones, epilepsia, dolor, enfermedades cardiacas, entre otras. |
| CL2008000836A1 (es) * | 2007-03-26 | 2008-11-07 | Actelion Pharmaceuticals Ltd | Compuestos derivados de tiazolidina, antagonistas del receptor de orexina; composicion farmaceutica que los comprende; y su uso en el tratamiento de neurosis emocional, depresion grave, trastornos psicoticos, alzheimer, parkinson, dolor, entre otras. |
| AU2008255005B2 (en) | 2007-05-18 | 2013-05-02 | Merck Sharp & Dohme Corp. | OXO bridged diazepan orexin receptor antagonists |
| US8030495B2 (en) | 2007-05-23 | 2011-10-04 | Coleman Paul J | Cyclopropyl pyrrolidine orexin receptor antagonists |
| HRP20120240T1 (hr) | 2007-05-23 | 2012-04-30 | Merck Sharp & Dohme Corp. | Piridil piperidin antagonisti receptora za oreksin |
| DK2170930T3 (da) | 2007-06-04 | 2012-11-05 | Synergy Pharmaceuticals Inc | Agonister af guanylatcyclase, anvendelige til behandlingen af gastrointestinale sygdomme, inflammation, cancer og andre sygdomme |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| CA2691373A1 (en) * | 2007-07-03 | 2009-01-08 | Actelion Pharmaceuticals Ltd | 3-aza-bicyclo[3.3.0]octane compounds |
| NZ583487A (en) * | 2007-07-27 | 2011-09-30 | Actelion Pharmaceuticals Ltd | 2-aza-bicyclo[3.3.0]octane derivatives |
| AR067665A1 (es) | 2007-07-27 | 2009-10-21 | Actelion Pharmaceuticals Ltd | Derivados de trans-3- aza-biciclo ( 3.1.0) hexano |
| EP2207778A2 (en) | 2007-09-24 | 2010-07-21 | Actelion Pharmaceuticals Ltd. | Pyrrolidines and piperidines as orexin receptor antagonists |
| NZ588080A (en) | 2008-02-21 | 2012-04-27 | Actelion Pharmaceuticals Ltd | 2-Aza-bicyclo[2.2.1]heptane derivatives |
| CA2722347A1 (en) * | 2008-04-30 | 2009-11-05 | Actelion Pharmaceuticals Ltd | Piperidine and pyrrolidine compounds |
| EP2328910B1 (en) | 2008-06-04 | 2014-08-06 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| CA2729985A1 (en) * | 2008-07-07 | 2010-01-14 | Actelion Pharmaceuticals Ltd | Thiazolidine compounds as orexin receptor antagonists |
| ES2624828T3 (es) | 2008-07-16 | 2017-07-17 | Synergy Pharmaceuticals Inc. | Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros |
| US8410284B2 (en) | 2008-10-22 | 2013-04-02 | Merck Sharp & Dohme Corp | Cyclic benzimidazole derivatives useful as anti-diabetic agents |
| EP2362731B1 (en) | 2008-10-31 | 2016-04-06 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| BRPI0922353A2 (pt) | 2008-12-02 | 2018-06-05 | Glaxo Group Ltd | Derivados de n-{[(1r,4s, 6r-3- (2-piridinilcarbonil) - 3azabiciclo [4.1.0] hept-4-il] metil}-2-heteroarilamina e usos dos mesmos |
| GB0823467D0 (en) | 2008-12-23 | 2009-01-28 | Glaxo Group Ltd | Novel Compounds |
| EP2421850A1 (en) | 2009-04-24 | 2012-02-29 | Glaxo Group Limited | 3 -azabicyclo [4.1.0]heptanes used as orexin antagonists |
| EP2470523A1 (en) | 2009-08-24 | 2012-07-04 | Glaxo Group Limited | 5-methyl-piperidine derivatives as orexin receptor antagonists for the treatment of sleep disorder |
| JP2013502448A (ja) | 2009-08-24 | 2013-01-24 | グラクソ グループ リミテッド | オレキシンアンタゴニストとして用いられるピペリジン誘導体 |
| JP2013520502A (ja) | 2010-02-25 | 2013-06-06 | メルク・シャープ・エンド・ドーム・コーポレイション | 有用な抗糖尿病薬である新規な環状ベンズイミダゾール誘導体 |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| WO2012089607A1 (en) | 2010-12-28 | 2012-07-05 | Glaxo Group Limited | Novel compounds with a 3a-azabicyclo [4.1.0] heptane core acting on orexin receptors |
| WO2012089606A1 (en) | 2010-12-28 | 2012-07-05 | Glaxo Group Limited | Azabicyclo [4.1.0] hept - 4 - yl derivatives as human orexin receptor antagonists |
| SG192941A1 (en) | 2011-02-25 | 2013-09-30 | Merck Sharp & Dohme | Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agents |
| AR088352A1 (es) | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
| US9440982B2 (en) | 2012-02-07 | 2016-09-13 | Eolas Therapeutics, Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| EP2811997B1 (en) | 2012-02-07 | 2018-04-11 | Eolas Therapeutics Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| LT2855453T (lt) | 2012-06-04 | 2017-02-27 | Actelion Pharmaceuticals Ltd. | Benzimidazolo prolino dariniai |
| WO2014022528A1 (en) | 2012-08-02 | 2014-02-06 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| US9493446B2 (en) | 2012-10-10 | 2016-11-15 | Actelion Pharmaceuticals Ltd. | Orexin receptor antagonists which are [ortho bi-(hetero-)aryl]-[2-(meta bi-(hetero-)aryl)-pyrrolidin-1-yl]-methanone derivatives |
| JP2016516004A (ja) | 2013-02-22 | 2016-06-02 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | 抗糖尿病二環式化合物 |
| EP2970241A1 (en) | 2013-03-12 | 2016-01-20 | Actelion Pharmaceuticals Ltd. | Azetidine amide derivatives as orexin receptor antagonists |
| EP2970119B1 (en) | 2013-03-14 | 2021-11-03 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
| CA2905438A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| US9486494B2 (en) | 2013-03-15 | 2016-11-08 | Synergy Pharmaceuticals, Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| JP6606491B2 (ja) | 2013-06-05 | 2019-11-13 | シナジー ファーマシューティカルズ インコーポレイテッド | グアニル酸シクラーゼｃの超高純度アゴニスト、その作成および使用方法 |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| UA119151C2 (uk) | 2013-12-03 | 2019-05-10 | Ідорсія Фармасьютікалз Лтд | КРИСТАЛІЧНА СОЛЬОВА ФОРМА (S)-(2-(6-ХЛОР-7-МЕТИЛ-1H-БЕНЗО[d]ІМІДАЗОЛ-2-ІЛ)-2-МЕТИЛПІРОЛІДИН-1-ІЛ)(5-МЕТОКСИ-2-(2H-1,2,3-ТРИАЗОЛ-2-ІЛ)ФЕНІЛ)МЕТАНОНУ ЯК АНТАГОНІСТ ОРЕКСИНОВОГО РЕЦЕПТОРА |
| PT3077389T (pt) | 2013-12-03 | 2017-12-15 | Idorsia Pharmaceuticals Ltd | Forma cristalina de (s)-(2-(6-cloro-7-metil-1hbenzo[d]imidazol-2-il)-2-metilpirrolidin-1-il)(5-metoxi-2-(2h-1,2,3-triazol-2-il)fenil)metanona e a sua utilização como como antagonistas do receptor de orexina |
| SI3077391T1 (sl) | 2013-12-04 | 2018-11-30 | Idorsia Pharmaceuticals Ltd | Uporaba benzimidazol-prolinskih derivatov |
| WO2016025669A1 (en) | 2014-08-13 | 2016-02-18 | Eolas Therapeutics, Inc. | Difluoropyrrolidines as orexin receptor modulators |
| PL3414241T3 (pl) | 2016-02-12 | 2022-10-03 | Astrazeneca Ab | Piperydyny podstawione halo jako modulatory receptora oreksyny |
| EP3454857A1 (en) | 2016-05-10 | 2019-03-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of autoimmune inflammatory diseases |
| WO2018106518A1 (en) | 2016-12-06 | 2018-06-14 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
| WO2018118670A1 (en) | 2016-12-20 | 2018-06-28 | Merck Sharp & Dohme Corp. | Antidiabetic spirochroman compounds |
| WO2020007964A1 (en) | 2018-07-05 | 2020-01-09 | Idorsia Pharmaceuticals Ltd | 2-(2-azabicyclo[3.1.0]hexan-1-yl)-1h-benzimidazole derivatives |
| WO2020099511A1 (en) | 2018-11-14 | 2020-05-22 | Idorsia Pharmaceuticals Ltd | Benzimidazole-2-methyl-morpholine derivatives |
| KR20220016918A (ko) | 2019-06-04 | 2022-02-10 | 하거 바이오사이언시즈, 엘엘씨 | 오렉신 길항제로서의 이미다졸로 유도체, 조성물 및 방법 |
| TW202400149A (zh) | 2022-05-13 | 2024-01-01 | 瑞士商愛杜西亞製藥有限公司 | 經噻唑并芳基-甲基取代之環狀肼-n-甲醯胺衍生物 |
| GB202311281D0 (en) * | 2023-07-21 | 2023-09-06 | Bial Portela & Ca Sa | Orexin receptor antagonists |
| GB202311280D0 (en) * | 2023-07-21 | 2023-09-06 | Bial Portela & Ca Sa | Orexin receptor antagonists |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3621775A1 (de) | 1986-03-13 | 1988-01-07 | Thomae Gmbh Dr K | Neue substituierte thiazole und oxazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| US4870074A (en) * | 1986-04-30 | 1989-09-26 | Dainippon Pharmaceutical Co., Ltd. | Substituted benzamide derivatives, for enhancing gastrointestinal motility |
| GB8813714D0 (en) * | 1988-06-09 | 1988-07-13 | Glaxo Group Ltd | Chemical compounds |
| US5719147A (en) * | 1992-06-29 | 1998-02-17 | Merck & Co., Inc. | Morpholine and thiomorpholine tachykinin receptor antagonists |
| EP1144409B1 (en) | 1999-02-12 | 2004-11-17 | SmithKline Beecham plc | Phenyl urea and phenyl thiourea derivatives |
| DE60013250T2 (de) * | 1999-02-12 | 2005-09-08 | Smithkline Beecham P.L.C., Brentford | Phenylharnstoff- und Phenylthioharnstoffderivate als Orexinrezeptorantagonisten |
| FR2791346B3 (fr) * | 1999-03-25 | 2001-04-27 | Sanofi Sa | Nouveaux derives de morpholine, procede pour leur preparation et compositions pharmaceutiques les contenant |
| US6635661B2 (en) * | 2000-05-25 | 2003-10-21 | Sepracor Inc. | Heterocyclic analgesic compounds and methods of use thereof |
| US6677332B1 (en) * | 1999-05-25 | 2004-01-13 | Sepracor, Inc. | Heterocyclic analgesic compounds and methods of use thereof |
| JP4009460B2 (ja) * | 2000-03-14 | 2007-11-14 | アクテリオン ファマシューティカルズ リミテッド | １，２，３，４−テトラヒドロイソキノリン誘導体 |
| PT1289955E (pt) * | 2000-06-16 | 2005-08-31 | Smithkline Beecham Plc | Piperidinas para utilizacao como antagonistas dos receptores da orexina |
| HUP0302302A2 (hu) * | 2000-09-29 | 2003-12-29 | Glaxo Group Limited | Morfolin-acetamid-származékok gyulladásos betegségek kezelésére, eljárás az előállításukra és ezeket tartalmazó gyógyszerkészítmények |
| GB0130335D0 (en) * | 2001-12-19 | 2002-02-06 | Smithkline Beecham Plc | Compounds |
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2001
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- 2001-11-22 JP JP2002546542A patent/JP4246490B2/ja not_active Expired - Fee Related
- 2001-11-22 DE DE60108420T patent/DE60108420T2/de not_active Expired - Lifetime
- 2001-11-22 AT AT01994716T patent/ATE286897T1/de not_active IP Right Cessation
- 2001-11-22 ES ES01994716T patent/ES2234929T3/es not_active Expired - Lifetime
- 2001-11-22 US US10/432,421 patent/US6943160B2/en not_active Expired - Fee Related
- 2001-11-22 AU AU2002224885A patent/AU2002224885A1/en not_active Abandoned
- 2001-11-22 EP EP01994716A patent/EP1353918B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US6943160B2 (en) | 2005-09-13 |
| US20040058921A1 (en) | 2004-03-25 |
| EP1353918B1 (en) | 2005-01-12 |
| JP2004521087A (ja) | 2004-07-15 |
| WO2002044172A1 (en) | 2002-06-06 |
| EP1353918A1 (en) | 2003-10-22 |
| JP4246490B2 (ja) | 2009-04-02 |
| ATE286897T1 (de) | 2005-01-15 |
| DE60108420D1 (en) | 2005-02-17 |
| ES2234929T3 (es) | 2005-07-01 |
| AU2002224885A1 (en) | 2002-06-11 |
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| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |