CA2827642A1 - Compounds and methods of treating diabetes - Google Patents
Compounds and methods of treating diabetes Download PDFInfo
- Publication number
- CA2827642A1 CA2827642A1 CA 2827642 CA2827642A CA2827642A1 CA 2827642 A1 CA2827642 A1 CA 2827642A1 CA 2827642 CA2827642 CA 2827642 CA 2827642 A CA2827642 A CA 2827642A CA 2827642 A1 CA2827642 A1 CA 2827642A1
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- optionally substituted
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
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- C07—ORGANIC CHEMISTRY
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- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
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- 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
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- C07D471/12—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 three hetero rings
- C07D471/14—Ortho-condensed systems
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- C07D471/12—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 three hetero rings
- C07D471/18—Bridged systems
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- C07D471/22—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 systems contains four or more hetero rings
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| PCT/US2012/025749 WO2012154261A1 (en) | 2011-02-18 | 2012-02-17 | Compounds and methods of treating diabetes |
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Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6302875B1 (en) | 1996-10-11 | 2001-10-16 | Transvascular, Inc. | Catheters and related devices for forming passageways between blood vessels or other anatomical structures |
| US20080213331A1 (en) | 2002-04-08 | 2008-09-04 | Ardian, Inc. | Methods and devices for renal nerve blocking |
| US20070129761A1 (en) | 2002-04-08 | 2007-06-07 | Ardian, Inc. | Methods for treating heart arrhythmia |
| US7617005B2 (en) | 2002-04-08 | 2009-11-10 | Ardian, Inc. | Methods and apparatus for thermally-induced renal neuromodulation |
| US8150519B2 (en) | 2002-04-08 | 2012-04-03 | Ardian, Inc. | Methods and apparatus for bilateral renal neuromodulation |
| US7653438B2 (en) | 2002-04-08 | 2010-01-26 | Ardian, Inc. | Methods and apparatus for renal neuromodulation |
| US9636174B2 (en) | 2002-04-08 | 2017-05-02 | Medtronic Ardian Luxembourg S.A.R.L. | Methods for therapeutic renal neuromodulation |
| US20070135875A1 (en) | 2002-04-08 | 2007-06-14 | Ardian, Inc. | Methods and apparatus for thermally-induced renal neuromodulation |
| EP1819304B1 (en) | 2004-12-09 | 2023-01-25 | Twelve, Inc. | Aortic valve repair |
| RU2007139634A (ru) | 2007-10-25 | 2009-04-27 | Сергей Олегович Бачурин (RU) | Новые тиазол-, триазол- или оксадиазол-содержащие тетрациклические соединения |
| RU2544856C2 (ru) | 2008-01-25 | 2015-03-20 | Сергей Олегович Бачурин | НОВЫЕ ПРОИЗВОДНЫЕ 2,3,4,5-ТЕТРАГИДРО-1-ПИРИДО[4,3-b]ИНДОЛА И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
| WO2009120720A1 (en) | 2008-03-24 | 2009-10-01 | Medivation Technologies,Inc. | Bridged heterocyclic compounds and methods of use |
| EP2280968A2 (en) | 2008-03-24 | 2011-02-09 | Medivation Technologies, Inc. | Pyrido [3, 4-b]indoles and methods of use |
| CA2742320A1 (en) | 2008-10-31 | 2010-05-06 | Medivation Technologies, Inc. | Pyrido[4,3-b]indoles containing rigid moieties |
| AU2009308708B2 (en) | 2008-10-31 | 2015-11-19 | Medivation Technologies, Inc. | Azepino [4, 5-b] indoles and methods of use |
| AU2010282990B2 (en) | 2009-04-29 | 2015-11-05 | Medivation Technologies, Inc. | Pyrido [4, 3-b] indoles and methods of use |
| EP2424364A4 (en) | 2009-04-29 | 2012-12-19 | Medivation Technologies Inc | PYRIDO [4.3-B] INDOLES AND METHODS OF USE |
| AU2010298168B2 (en) | 2009-09-23 | 2015-11-19 | Medivation Technologies, Inc. | Pyrido(3,4-b)indoles and methods of use |
| JP5779183B2 (ja) | 2009-09-23 | 2015-09-16 | メディベイション テクノロジーズ， インコーポレイテッド | ピリド［４，３−ｂ］インドールおよび使用方法 |
| AU2010298169B2 (en) | 2009-09-23 | 2015-10-29 | Medivation Technologies, Inc. | Bridged heterocyclic compounds and methods of use |
| WO2011103433A1 (en) | 2010-02-18 | 2011-08-25 | Medivation Technologies, Inc. | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| WO2011103485A1 (en) | 2010-02-18 | 2011-08-25 | Medivation Technologies, Inc. | Fused tetracyclic pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| US9193728B2 (en) | 2010-02-18 | 2015-11-24 | Medivation Technologies, Inc. | Fused tetracyclic pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use |
| US9187471B2 (en) | 2010-02-19 | 2015-11-17 | Medivation Technologies, Inc. | Pyrido [4,3-b] indole and pyrido [3,4-b] indole derivatives and methods of use |
| WO2012112962A1 (en) | 2011-02-18 | 2012-08-23 | Medivation Technologies, Inc. | Compounds and methods of treating diabetes |
| US20140303144A1 (en) | 2011-02-18 | 2014-10-09 | Medivation Technologies, Inc. | Compounds and methods of treating hypertension |
| US9035056B2 (en) | 2011-02-18 | 2015-05-19 | Medivation Technologies, Inc. | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| IN2013MN01699A (enExample) | 2011-02-18 | 2015-06-12 | Medivation Technologies Inc | |
| WO2012161875A1 (en) | 2011-04-08 | 2012-11-29 | Tyco Healthcare Group Lp | Iontophoresis drug delivery system and method for denervation of the renal sympathetic nerve and iontophoretic drug delivery |
| JP5958772B2 (ja) * | 2011-11-18 | 2016-08-02 | 時人 雪村 | 腎障害の治療又は予防薬 |
| EP2887805A4 (en) * | 2012-08-22 | 2016-08-17 | Medivation Technologies Inc | COMPOUNDS AND METHOD FOR TREATING BLOOD HIGH PRESSURE |
| EA201690880A1 (ru) * | 2013-11-22 | 2016-12-30 | Фармакеа, Инк. | Тетрациклические ингибиторы аутотаксина |
| KR102515248B1 (ko) | 2013-11-22 | 2023-03-29 | 사브레 테라퓨틱스 엘엘씨 | 오토탁신 억제제 화합물 |
| EA039684B1 (ru) | 2015-05-27 | 2022-02-28 | Сабре Терапьютикс Ллс | Ингибиторы аутотаксина и их применения |
| WO2018064465A1 (en) | 2016-09-29 | 2018-04-05 | The Regents Of The University Of California | Compounds for increasing neural plasticity |
| US11116561B2 (en) | 2018-01-24 | 2021-09-14 | Medtronic Ardian Luxembourg S.A.R.L. | Devices, agents, and associated methods for selective modulation of renal nerves |
| CA3130770A1 (en) | 2019-02-27 | 2020-09-03 | The Regents Of The University Of California | Azepino-indoles and other heterocycles for treating brain disorders |
| WO2022225839A1 (en) * | 2021-04-20 | 2022-10-27 | Bacainn Therapeutics, Inc. | Cyclosporine compositions and methods of use |
| TW202333668A (zh) | 2021-12-15 | 2023-09-01 | 美商德利克斯醫療公司 | 經苯氧基及苄氧基取代之精神成形素(psychoplastogen)及其用途 |
| KR20230171634A (ko) * | 2022-06-14 | 2023-12-21 | 주식회사 레고켐 바이오사이언스 | 엑토뉴클레오티드 피로포스파타아제 포스포디에스터라아제-1 저해 화합물 및 이를 함유하는 약제학적 조성물 |
Family Cites Families (107)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2642438A (en) | 1949-07-15 | 1953-06-16 | Hoffmann La Roche | Pyridindoles and method of manufacture |
| GB721171A (en) | 1951-04-30 | 1954-12-29 | Bayer Ag | Derivatives of ª‰- and ª†- carbolines |
| CH445508A (de) | 1964-12-03 | 1967-10-31 | Geigy Ag J R | Verfahren zur Herstellung von neuen Indolderivaten |
| US3484449A (en) * | 1966-05-12 | 1969-12-16 | Hoffmann La Roche | Certain substituted phenyl amino-ethylpyridine intermediates |
| US3409628A (en) | 1966-05-12 | 1968-11-05 | Hoffmann La Roche | 5-(3-pyridylethyl)pyridoindole derivatives |
| US3525750A (en) | 1966-05-31 | 1970-08-25 | Geigy Chem Corp | 1,2,3,4,5,6-hexahydro-azepino(4,5-b) indole derivatives |
| US3502688A (en) | 1968-09-10 | 1970-03-24 | Hoffmann La Roche | 5-(4-pyridylethyl)-pyridoindole derivatives |
| US3646045A (en) | 1968-09-10 | 1972-02-29 | Hoffmann La Roche | Intermediates for 5-(4-pyridylethyl)-pyridoindole derivatives |
| SE7804318L (sv) | 1977-05-02 | 1978-11-03 | Merck & Co Inc | Nya naftyridiner |
| FR2516512A1 (fr) | 1981-11-19 | 1983-05-20 | Corbiere Jerome | Nouveaux derives pyridoindoliques, leur procede de preparation et les compositions pharmaceutiques en contenant |
| JPS63163347A (ja) | 1986-12-25 | 1988-07-06 | Konica Corp | 有機着色物質の光褪色防止方法 |
| US4754038A (en) | 1987-02-26 | 1988-06-28 | American Home Products Corporation | Carboline histamine H1 antagonists |
| US5360800A (en) | 1987-09-03 | 1994-11-01 | Glaxo Group Limited | Tetrahydro-1H-pyrido[4,3-b]indol-1-one derivatives |
| EP0353983B1 (en) | 1988-08-02 | 1996-05-29 | Glaxo Group Limited | Lactam derivatives |
| FR2663935A1 (fr) | 1990-06-27 | 1992-01-03 | Adir | Nouveaux 1,2,3,4,5,6-hexahydroazepino [4,5-b] indoles et 1,2,3,4-tetrahydrobethacarbolines, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
| US5273977A (en) | 1990-11-05 | 1993-12-28 | Warner-Lambert Company | Substituted tetrahydropyridines and hydroxypiperidines as central nervous system agents |
| US5250537A (en) | 1992-03-13 | 1993-10-05 | Scios Nova Inc. | 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole,-6,7,8,9,10-hexahydro-7,11-imino-5H-cyclooct[b]indole and substituted derivatives |
| US5688807A (en) | 1994-03-11 | 1997-11-18 | Eli Lilly And Company | Method for treating 5HT2B receptor related conditions |
| EP0823909B1 (en) | 1995-05-05 | 2002-09-11 | British Technology Group Inter-Corporate Licensing Limited | Novel heterocyclic chemistry |
| RU2140417C1 (ru) | 1995-10-17 | 1999-10-27 | Институт физиологически активных веществ РАН | Производные гидрированных пиридо(4,3-b)индолов, способы их получения, фармацевтическая композиция и способ лечения |
| RU2106864C1 (ru) | 1995-10-23 | 1998-03-20 | Николай Серафимович Зефиров | Средство для лечения болезни альцгеймера |
| TW470745B (en) | 1996-05-23 | 2002-01-01 | Janssen Pharmaceutica Nv | Hexahydro-pyrido[4,3-b]indole derivatives |
| JP2001522884A (ja) | 1997-11-14 | 2001-11-20 | イーライ・リリー・アンド・カンパニー | アルツハイマー病の処置方法 |
| US6251893B1 (en) | 1998-06-15 | 2001-06-26 | Nps Allelix Corp. | Bicyclic piperidine and piperazine compounds having 5-HT6 receptor affinity |
| FR2796644B1 (fr) | 1999-07-23 | 2001-09-07 | Adir | Nouveaux derives de beta-carboline, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| EP1254115A2 (en) * | 2000-02-11 | 2002-11-06 | Bristol-Myers Squibb Company | Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators for treating respiratory and non-respiratory diseases |
| DE10030375A1 (de) | 2000-06-21 | 2002-01-03 | Bayer Ag | Verwendung von MTP-Inhibitoren zur Senkung von ppTRL |
| JP2004509894A (ja) * | 2000-09-20 | 2004-04-02 | ファルマシア・アンド・アップジョン・カンパニー | 置換アゼピノ［４，５−ｂ］インドリン誘導体 |
| CA2453537A1 (en) | 2001-08-08 | 2003-02-20 | Pharmacia & Upjohn Company | Therapeutic 1h-pyrido¬4,3-b|indoles |
| JP2005523892A (ja) | 2002-01-18 | 2005-08-11 | アリックス セラピューティクス | ５−ｈｔ３受容体アンタゴニストおよび使用法 |
| US7595311B2 (en) | 2002-05-24 | 2009-09-29 | Exelixis, Inc. | Azepinoindole derivatives as pharmaceutical agents |
| US7759336B2 (en) | 2002-12-10 | 2010-07-20 | Ono Pharmaceutical Co., Ltd. | Nitrogen-containing heterocyclic compounds and medicinal use thereof |
| US7736889B2 (en) | 2003-06-10 | 2010-06-15 | The United States Of America As Represented By The Secretary Of The Navy | Fluidic force discrimination |
| US20060293359A1 (en) | 2003-06-25 | 2006-12-28 | Allergan, Inc. | Methods and compositions for the treatment of diabetes |
| WO2005031301A2 (en) | 2003-07-10 | 2005-04-07 | Parallax Biosystems, Inc. | Raman signature probes and their use in the detection and imaging of molecular processes and structures |
| US8466143B2 (en) * | 2003-07-23 | 2013-06-18 | Exelixis, Inc. | Azepine derivatives as pharmaceutical agents |
| US20050143371A1 (en) | 2003-07-23 | 2005-06-30 | Pharmacia Corporation | Beta-carboline compounds and analogues thereof as mitogen-activated protein kinase-activated protein kinase-2 inhibitors |
| US20070179174A1 (en) | 2003-12-08 | 2007-08-02 | Bachurin Sergei O | Methods and compositions for slowing aging |
| RU2283108C2 (ru) | 2003-12-08 | 2006-09-10 | Сергей Олегович Бачурин | ГЕРОПРОТЕКТОР НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО(4,3-b) ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| BRPI0517211B8 (pt) | 2004-12-17 | 2021-05-25 | Glenmark Pharmaceuticals Sa | composto, composição farmacêutica e seu uso. |
| EP1863810A4 (en) | 2005-03-22 | 2010-03-31 | Astrazeneca Ab | NEW TETRAHYDRO-1H-PYRIDO [4,3-B] INDOLDERIVATE AS CB1 'RECEPTOR LIGANDS |
| EP1902044A1 (en) | 2005-07-07 | 2008-03-26 | Bio Medisinsk Innovasjon AS | 5-htx modulators |
| KR20080034171A (ko) | 2005-07-28 | 2008-04-18 | 브리스톨-마이어스 스큅 컴퍼니 | 세로토닌 수용체 효능제 및 길항제로서의 치환된테트라히드로-1ｈ-피리도[4,3,ｂ]인돌 |
| WO2007024651A2 (en) | 2005-08-19 | 2007-03-01 | Elan Pharmaceuticals, Inc. | Bridged n-bicyclic sulfonamido inhibitors of gamma secretase |
| CA2624731A1 (en) | 2005-10-04 | 2007-04-12 | Medivation, Inc. | Hydrogenated pyrido-indole compounds for the treatment of huntington's disease |
| RU2338537C2 (ru) | 2006-01-25 | 2008-11-20 | Сергей Олегович Бачурин | СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ШИЗОФРЕНИИ НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО(4,3-b)ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| US20100099700A1 (en) | 2006-09-20 | 2010-04-22 | David Hung | Hydrogenated pyrido (4,3-b) indoles for treating amyotrophic lateral sclerosis (als) |
| JP2010504337A (ja) | 2006-09-20 | 2010-02-12 | メディベイション ニューロロジー， インコーポレイテッド | イヌの認知機能障害症候群の治療のためのディメボン（ｄｉｍｅｂｏｎ）などの水素化ピリド［４，３−ｂ］インドール |
| ATE549021T1 (de) | 2006-10-27 | 2012-03-15 | Medivation Neurology Inc | Kombinationstherapien zur behandlung von morbus alzheimer mit dimebon und donepezil |
| RU2329044C1 (ru) | 2006-11-16 | 2008-07-20 | Андрей Александрович Иващенко | Лиганды 5-ht6 рецепторов, фармацевтическая композиция, способ ее получения и лекарственное средство |
| RU2334514C1 (ru) | 2006-12-01 | 2008-09-27 | Институт физиологически активных веществ Российской Академии наук | СРЕДСТВО ДЛЯ УЛУЧШЕНИЯ КОГНИТИВНЫХ ФУНКЦИЙ И ПАМЯТИ НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО (4,3-b) ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| RU2340342C2 (ru) | 2006-12-07 | 2008-12-10 | Сергей Олегович Бачурин | СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ОСТРЫХ И ХРОНИЧЕСКИХ НАРУШЕНИЙ МОЗГОВОГО КРОВООБРАЩЕНИЯ, В ТОМ ЧИСЛЕ ИНСУЛЬТА, НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО[4,3-b]ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| RU2338745C1 (ru) | 2007-03-21 | 2008-11-20 | Андрей Александрович Иващенко | ЗАМЕЩЕННЫЕ 2,3,4,5-ТЕТРАГИДРО-1Н-ПИРИДО[4,3-b]ИНДОЛЫ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ |
| KR20090130105A (ko) | 2007-04-05 | 2009-12-17 | 알라 캠, 엘엘씨 | 치환된 2,3,4,5-테트라히드로-1ｈ-피리도［4,3-ｂ］ 인돌, 그 제조방법 및 용도 |
| RU2339637C1 (ru) | 2007-04-05 | 2008-11-27 | Андрей Александрович Иващенко | Блокаторы гистаминного рецептора для фармацевтических композиций, обладающих противоаллергическим и аутоиммунным действием |
| WO2008133867A1 (en) | 2007-04-26 | 2008-11-06 | Merck & Co., Inc. | 2-substituted indole derivatives as calcium channel blockers |
| CA2688327A1 (en) | 2007-05-25 | 2008-12-04 | Medivation Neurology, Inc. | Methods and compositions for stimulating cells |
| JP2010531344A (ja) | 2007-06-26 | 2010-09-24 | アストラゼネカ アクチボラグ | カテプシンｋ阻害剤としての１−シアノシクロプロピル誘導体 |
| RU2338533C1 (ru) * | 2007-06-28 | 2008-11-20 | Сергей Олегович Бачурин | СРЕДСТВО, ОБЛАДАЮЩЕЕ АНКСИОЛИТИЧЕСКИМ ДЕЙСТВИЕМ, НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО(4,3-b)ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| WO2009017836A1 (en) | 2007-08-01 | 2009-02-05 | Medivation Neurology, Inc. | Methods and compositions for treating schizophrenia using antipsychotic combination therapy |
| CN101868234A (zh) | 2007-09-20 | 2010-10-20 | D2E有限公司 | 具有神经保护和认知增强特性的氢化吡啶并[4,3-b]吲哚的含氟衍生物,其制备方法及应用 |
| WO2009039420A1 (en) | 2007-09-21 | 2009-03-26 | Medivation Neurology, Inc. | Methods and compositions for treating neuronal death mediated ocular diseases |
| RU2007139634A (ru) | 2007-10-25 | 2009-04-27 | Сергей Олегович Бачурин (RU) | Новые тиазол-, триазол- или оксадиазол-содержащие тетрациклические соединения |
| EP2236511A4 (en) | 2007-12-21 | 2011-04-13 | Alla Chem Llc | LIGANDS OF ALPHA ADRENOCEPTORS AND OF DOPAMINE, HISTAMIN, IMIDAZOLIN AND SEROTONIN RECEPTORS AND THEIR APPLICATION THEREOF |
| RU2544856C2 (ru) | 2008-01-25 | 2015-03-20 | Сергей Олегович Бачурин | НОВЫЕ ПРОИЗВОДНЫЕ 2,3,4,5-ТЕТРАГИДРО-1-ПИРИДО[4,3-b]ИНДОЛА И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
| WO2009111540A1 (en) | 2008-03-04 | 2009-09-11 | Medivation Neurology, Inc. | Methods for preparing pyridylethyl-substituted carbolines |
| ES2602577T3 (es) | 2008-03-11 | 2017-02-21 | Incyte Holdings Corporation | Derivados de azetidina y ciclobutano como inhibidores de JAK |
| WO2009120720A1 (en) | 2008-03-24 | 2009-10-01 | Medivation Technologies,Inc. | Bridged heterocyclic compounds and methods of use |
| EP2280968A2 (en) | 2008-03-24 | 2011-02-09 | Medivation Technologies, Inc. | Pyrido [3, 4-b]indoles and methods of use |
| US8293758B2 (en) | 2008-03-27 | 2012-10-23 | Grunenthal Gmbh | Substituted spirocyclic cyclohexane derivatives |
| WO2009135091A1 (en) | 2008-04-30 | 2009-11-05 | Medivation Technologies, Inc. | Use of asenapine and related compounds for the treatment of neuronal or non-neuronal diseases or conditions |
| UY31831A (es) | 2008-05-20 | 2010-01-05 | Astrazeneca Ab | Derivados de indazoles sustituidos con fenilo o piridinilo |
| DE102008030206A1 (de) | 2008-06-25 | 2009-12-31 | Bayer Schering Pharma Aktiengesellschaft | 3-Cyanoalky- und 3-Hydroxyalkyl-Indole und ihre Verwendung |
| US20100029706A1 (en) | 2008-07-30 | 2010-02-04 | Edison Parmaceuticals, Inc. a Delaware Corporation | HYDROGENATED PYRIDO[4,3-b]INDOLES FOR THE TREATMENT OF OXIDATIVE STRESS |
| TW201018694A (en) | 2008-09-29 | 2010-05-16 | Abbott Lab | Indole and indoline derivatives and methods of use thereof |
| US9625475B2 (en) | 2008-09-29 | 2017-04-18 | Abbvie Inc. | Indole and indoline derivatives and methods of use thereof |
| AU2009308708B2 (en) * | 2008-10-31 | 2015-11-19 | Medivation Technologies, Inc. | Azepino [4, 5-b] indoles and methods of use |
| CA2742320A1 (en) * | 2008-10-31 | 2010-05-06 | Medivation Technologies, Inc. | Pyrido[4,3-b]indoles containing rigid moieties |
| WO2010057104A2 (en) * | 2008-11-17 | 2010-05-20 | Auspex Pharmaceuticals, Inc. | Pyridoindole modulators of nmda receptor and acetylcholinesterase |
| WO2010060037A2 (en) * | 2008-11-21 | 2010-05-27 | Auspex Pharmaceuticals, Inc. | Adamantane modulators of nmda receptor and/or 5ht3 receptor |
| US8362277B2 (en) | 2009-01-09 | 2013-01-29 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| EP2385829B1 (en) | 2009-01-09 | 2018-08-01 | Board of Regents of the University of Texas System | Pro-neurogenic compounds |
| US9962368B2 (en) | 2009-01-09 | 2018-05-08 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| EP2424364A4 (en) * | 2009-04-29 | 2012-12-19 | Medivation Technologies Inc | PYRIDO [4.3-B] INDOLES AND METHODS OF USE |
| AU2010282990B2 (en) | 2009-04-29 | 2015-11-05 | Medivation Technologies, Inc. | Pyrido [4, 3-b] indoles and methods of use |
| WO2011008312A2 (en) | 2009-07-14 | 2011-01-20 | Abbott Laboratories | Indole and indoline derivatives and methods of use thereof |
| RU2009128817A (ru) | 2009-07-28 | 2011-02-10 | Общество с ограниченной ответственностью "Инномед" (RU) | Производные гидрированных пиридо[4,3-b]индолов, фармацевтическая композиция, способы получения и применения |
| WO2011014695A1 (en) | 2009-07-29 | 2011-02-03 | Medivation Technologies, Inc. | New 2,3,4,5-tetrahydro-1h-pyrido[4,3-b] indoles and methods of use |
| AU2010298168B2 (en) | 2009-09-23 | 2015-11-19 | Medivation Technologies, Inc. | Pyrido(3,4-b)indoles and methods of use |
| US20130137705A1 (en) | 2009-09-23 | 2013-05-30 | Sarvajit Chakravarty | Pyrido[3,4-b]indoles and methods of use |
| JP5779183B2 (ja) | 2009-09-23 | 2015-09-16 | メディベイション テクノロジーズ， インコーポレイテッド | ピリド［４，３−ｂ］インドールおよび使用方法 |
| AU2010298169B2 (en) | 2009-09-23 | 2015-10-29 | Medivation Technologies, Inc. | Bridged heterocyclic compounds and methods of use |
| WO2011103485A1 (en) | 2010-02-18 | 2011-08-25 | Medivation Technologies, Inc. | Fused tetracyclic pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| US20130172320A1 (en) | 2010-02-18 | 2013-07-04 | Sarvajit Chakravarty | Pyrido [4,3-b] indole and pyrido [3,4-b] indole derivatives and methods of use |
| WO2011103433A1 (en) | 2010-02-18 | 2011-08-25 | Medivation Technologies, Inc. | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| US9193728B2 (en) | 2010-02-18 | 2015-11-24 | Medivation Technologies, Inc. | Fused tetracyclic pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use |
| US9187471B2 (en) | 2010-02-19 | 2015-11-17 | Medivation Technologies, Inc. | Pyrido [4,3-b] indole and pyrido [3,4-b] indole derivatives and methods of use |
| WO2011103448A1 (en) | 2010-02-19 | 2011-08-25 | Medivation Technologies, Inc. | Methods and compositions for treating psychotic disorders using antipsychotic combination therapy |
| CN103415289B (zh) | 2010-07-07 | 2017-04-12 | 得克萨斯州大学系统董事会 | 前神经原性化合物 |
| WO2012088038A2 (en) | 2010-12-21 | 2012-06-28 | Albany Molecular Research, Inc. | Piperazinone-substituted tetrahydro-carboline mch-1 antagonists, methods of making, and uses thereof |
| WO2012112962A1 (en) | 2011-02-18 | 2012-08-23 | Medivation Technologies, Inc. | Compounds and methods of treating diabetes |
| US9035056B2 (en) | 2011-02-18 | 2015-05-19 | Medivation Technologies, Inc. | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| US20140303144A1 (en) | 2011-02-18 | 2014-10-09 | Medivation Technologies, Inc. | Compounds and methods of treating hypertension |
| IN2013MN01699A (enExample) | 2011-02-18 | 2015-06-12 | Medivation Technologies Inc | |
| EP2887805A4 (en) | 2012-08-22 | 2016-08-17 | Medivation Technologies Inc | COMPOUNDS AND METHOD FOR TREATING BLOOD HIGH PRESSURE |
| WO2014031170A1 (en) | 2012-08-22 | 2014-02-27 | Medivation Technologies, Inc. | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| EP2925129A4 (en) | 2012-08-24 | 2016-06-08 | Univ Texas | PRO-NEUROGENIC COMPOUNDS |
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| US9527854B2 (en) | 2016-12-27 |
| CN103476416A (zh) | 2013-12-25 |
| AU2012219251A1 (en) | 2013-05-02 |
| US8815843B2 (en) | 2014-08-26 |
| AU2012254158A1 (en) | 2013-05-02 |
| US9006263B2 (en) | 2015-04-14 |
| AU2012219251B2 (en) | 2016-05-12 |
| BR112013021126A2 (pt) | 2019-09-24 |
| EP2675459A4 (en) | 2014-08-06 |
| WO2012154261A1 (en) | 2012-11-15 |
| EP2675458A1 (en) | 2013-12-25 |
| EP2675458A4 (en) | 2014-08-06 |
| CN103476417A (zh) | 2013-12-25 |
| JP2014505737A (ja) | 2014-03-06 |
| EP2675459A1 (en) | 2013-12-25 |
| US20130053366A1 (en) | 2013-02-28 |
| CN103476416B (zh) | 2016-09-21 |
| US20130053367A1 (en) | 2013-02-28 |
| BR112013021125A2 (pt) | 2019-09-24 |
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