AU2012254158B2 - Compounds and methods of treating diabetes - Google Patents
Compounds and methods of treating diabetes Download PDFInfo
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- AU2012254158B2 AU2012254158B2 AU2012254158A AU2012254158A AU2012254158B2 AU 2012254158 B2 AU2012254158 B2 AU 2012254158B2 AU 2012254158 A AU2012254158 A AU 2012254158A AU 2012254158 A AU2012254158 A AU 2012254158A AU 2012254158 B2 AU2012254158 B2 AU 2012254158B2
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- C07D—HETEROCYCLIC COMPOUNDS
- 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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- C07D471/02—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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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 |
| US7617005B2 (en) | 2002-04-08 | 2009-11-10 | Ardian, Inc. | Methods and apparatus for thermally-induced renal neuromodulation |
| US7653438B2 (en) | 2002-04-08 | 2010-01-26 | Ardian, Inc. | Methods and apparatus for renal neuromodulation |
| US20070135875A1 (en) | 2002-04-08 | 2007-06-14 | Ardian, Inc. | Methods and apparatus for thermally-induced renal neuromodulation |
| US20070129761A1 (en) | 2002-04-08 | 2007-06-07 | Ardian, Inc. | Methods for treating heart arrhythmia |
| US9636174B2 (en) | 2002-04-08 | 2017-05-02 | Medtronic Ardian Luxembourg S.A.R.L. | Methods for therapeutic renal neuromodulation |
| US8150519B2 (en) | 2002-04-08 | 2012-04-03 | Ardian, Inc. | Methods and apparatus for bilateral renal neuromodulation |
| US20080213331A1 (en) | 2002-04-08 | 2008-09-04 | Ardian, Inc. | Methods and devices for renal nerve blocking |
| WO2006063199A2 (en) | 2004-12-09 | 2006-06-15 | The Foundry, 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 |
| PE20091717A1 (es) | 2008-03-24 | 2009-11-25 | Medivation Technologies Inc | Pirido[3,4-b] indoles como moduladores de receptores de histamina |
| AU2009308706C1 (en) | 2008-10-31 | 2016-01-21 | Medivation Technologies, Inc. | Pyrido (4,3-b) indoles containing rigid moieties |
| JP5551708B2 (ja) | 2008-10-31 | 2014-07-16 | 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 | アゼピノ［４，５−ｂ］インドール化合物およびその使用方法 |
| AU2010242910B2 (en) | 2009-04-29 | 2015-11-12 | Medivation Technologies, Inc. | Pyrido [4,3-b] indoles and methods of use |
| JP5827943B2 (ja) | 2009-04-29 | 2015-12-02 | 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］インドールおよびその使用方法 |
| AU2010298166B2 (en) | 2009-09-23 | 2015-09-17 | Medivation Technologies, Inc. | Pyrido[4,3-b]indoles and methods of use |
| CN102724875B (zh) * | 2009-09-23 | 2015-05-27 | 梅迪维新技术公司 | 吡啶并[3,4-b]吲哚化合物及其使用方法 |
| CN102711466A (zh) | 2009-09-23 | 2012-10-03 | 梅迪维新技术公司 | 桥连杂环化合物及其使用方法 |
| WO2011103460A1 (en) | 2010-02-18 | 2011-08-25 | Medivation Technologies, Inc. | Fused tetracyclic pyrido[4,3-b]indole and pyrido[3,4-b]ondole 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 |
| US9034865B2 (en) | 2010-02-18 | 2015-05-19 | Medivation Technologies, Inc. | 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 |
| IN2013MN01699A (Direct) | 2011-02-18 | 2015-06-12 | Medivation Technologies Inc | |
| WO2012112961A1 (en) | 2011-02-18 | 2012-08-23 | 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 |
| US9199985B2 (en) | 2011-02-18 | 2015-12-01 | Medivation Technologies, Inc. | Compounds and methods for treatment of hypertension |
| EP2694150A1 (en) | 2011-04-08 | 2014-02-12 | Covidien 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 |
| WO2014031165A1 (en) * | 2012-08-22 | 2014-02-27 | Medivation Technologies, Inc. | Compounds and methods of treating diabetes |
| CA2930735A1 (en) * | 2013-11-22 | 2015-05-28 | Pharmakea, Inc. | Tetracyclic autotaxin inhibitors |
| PT3071561T (pt) | 2013-11-22 | 2021-06-25 | Sabre Therapeutics Llc | Compostos inibidores de autotaxina |
| US10632104B2 (en) | 2015-05-27 | 2020-04-28 | Sabre Therapeutics Llc | Autotaxin inhibitors and uses thereof |
| US12343337B2 (en) | 2016-09-29 | 2025-07-01 | 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 |
| WO2020176599A1 (en) | 2019-02-27 | 2020-09-03 | The Regents Of The University Of California | Azepino-indoles and other heterocycles for treating brain disorders |
| US20240277798A1 (en) * | 2021-04-20 | 2024-08-22 | Bacainn Biotherapeutics, Ltd. | Cyclosporine compositions and methods of use |
| IL313455A (en) | 2021-12-15 | 2024-08-01 | Delix Therapeutics Inc | Phenoxy and benzyloxy modified psychroplastogens and their uses |
| KR20230171634A (ko) * | 2022-06-14 | 2023-12-21 | 주식회사 레고켐 바이오사이언스 | 엑토뉴클레오티드 피로포스파타아제 포스포디에스터라아제-1 저해 화합물 및 이를 함유하는 약제학적 조성물 |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3484449A (en) * | 1966-05-12 | 1969-12-16 | Hoffmann La Roche | Certain substituted phenyl amino-ethylpyridine intermediates |
| WO2009005771A1 (en) * | 2007-06-28 | 2009-01-08 | Medivation Neurology, Inc. | A drug demonstrating anxiolytic effect based on hydrogenated pyrido (4, 3-b) indoles, its pharmacological compound and application method |
| EP2145887A2 (en) * | 2007-04-05 | 2010-01-20 | Alla Chem, LLC. | Substituted 2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indoles, methods for the production and use thereof |
| WO2010051501A1 (en) * | 2008-10-31 | 2010-05-06 | Medivation Technologies, Inc. | Pyrido (4,3-b) indoles containing rigid moieties |
| US20100125085A1 (en) * | 2008-11-17 | 2010-05-20 | Auspex Pharmaceuticals, Inc. | Pyridoindole modulators of nmda receptor and acetylcholinesterase |
| US20100152163A1 (en) * | 2008-10-31 | 2010-06-17 | Hung David T | Azepino[4,5-b]indoles and methods of use |
| US20100173824A1 (en) * | 2002-05-24 | 2010-07-08 | Exelixis, Inc. | Azepinoindole Derivatives As Pharmaceutical Agents |
| WO2011103448A1 (en) * | 2010-02-19 | 2011-08-25 | Medivation Technologies, Inc. | Methods and compositions for treating psychotic disorders using antipsychotic combination therapy |
Family Cites Families (99)
| 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 |
| CH445511A (de) | 1964-12-03 | 1967-10-31 | Geigy Ag J R | Verfahren zur Herstellung von neuen Indolderivaten |
| 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 |
| US3646045A (en) | 1968-09-10 | 1972-02-29 | Hoffmann La Roche | Intermediates for 5-(4-pyridylethyl)-pyridoindole derivatives |
| US3502688A (en) | 1968-09-10 | 1970-03-24 | Hoffmann La Roche | 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 |
| NZ230154A (en) | 1988-08-02 | 1991-10-25 | Glaxo Group Ltd | Imidazolyl-substituted 6- or 7-membered ring lactam derivatives and pharmaceutical composition |
| 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 |
| ATE223915T1 (de) | 1995-05-05 | 2002-09-15 | British Tech Group Int | Neue heterozyklische chemie |
| 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 |
| WO1999025340A1 (en) | 1997-11-14 | 1999-05-27 | Eli Lilly And Company | Treatment for alzheimer's disease |
| 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 |
| WO2001058869A2 (en) * | 2000-02-11 | 2001-08-16 | Bristol-Myers Squibb Company | Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators in treating respiratory and non-respiratory diseases |
| DE10030375A1 (de) | 2000-06-21 | 2002-01-03 | Bayer Ag | Verwendung von MTP-Inhibitoren zur Senkung von ppTRL |
| PE20020510A1 (es) | 2000-09-20 | 2002-06-12 | Upjohn Co | DERIVADOS DE AZEPILO [4,5b] INDOLINA SUSTITUIDOS COMO LIGANDOS DE LOS RECEPTORES DE SEROTONINA (5-HT) |
| JP2005526691A (ja) | 2001-08-08 | 2005-09-08 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | 治療剤１Ｈ−ピリド［４，３−ｂ］インドール |
| CA2473392A1 (en) | 2002-01-18 | 2003-07-31 | Aryx Therapeutics | 5-ht3 receptor antagonists and methods of use |
| 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 |
| US20050137220A1 (en) | 2003-07-23 | 2005-06-23 | Pharmacia Corporation | Beta-carboline compounds and analogues thereof as mitogen-activated protein kinase-activated protein kinase-2 inhibitors |
| WO2005009387A2 (en) * | 2003-07-23 | 2005-02-03 | X-Ceptor Therapeutics Inc. | Azepine derivatives as pharmaceutical agents |
| 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 |
| US20070179174A1 (en) | 2003-12-08 | 2007-08-02 | Bachurin Sergei O | Methods and compositions for slowing aging |
| KR101317119B1 (ko) | 2004-12-17 | 2013-10-11 | 그렌마크 파머수티칼스 에스. 아. | 염증성 및 알레르기성 장애의 치료에 유용한 신규한헤테로사이클릭 화합물 |
| CN102030750A (zh) | 2005-03-22 | 2011-04-27 | 阿斯利康(瑞典)有限公司 | 用作CB1受体配体的新四氢-1H-吡啶并[4,3-b]吲哚衍生物 |
| EP1902044A1 (en) | 2005-07-07 | 2008-03-26 | Bio Medisinsk Innovasjon AS | 5-htx modulators |
| WO2007016353A2 (en) * | 2005-07-28 | 2007-02-08 | Bristol-Myers Squibb Company | Substituted tetrahydro-1h-pyrido[4,3,b]indoles as serotonin receptor agonists and antagonists |
| CN101426860A (zh) | 2005-08-19 | 2009-05-06 | 伊兰医药品股份有限公司 | γ-分泌酶的桥连N-环磺酰氨基抑制剂 |
| WO2007041697A2 (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 |
| AU2007297618A1 (en) | 2006-09-20 | 2008-03-27 | Medivation Neurology, Inc. | Hydrogenated pyrido [4,3-b] indoles such as dimebon for treating canine Cognitive Dysfunction Syndrome |
| EP2063892A2 (en) | 2006-09-20 | 2009-06-03 | Medivation Neurology, Inc. | Methods and compositions for treating amyotrophic lateral sclerosis (als) |
| KR20090087009A (ko) | 2006-10-27 | 2009-08-14 | 메디베이션 뉴롤로지 인코퍼레이티드 | 아이.에이. 다임본 및 도레페질을 사용하여 알츠하이머 병을 치료하기 위한 조합 요법 |
| 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 |
| RU2339637C1 (ru) | 2007-04-05 | 2008-11-27 | Андрей Александрович Иващенко | Блокаторы гистаминного рецептора для фармацевтических композиций, обладающих противоаллергическим и аутоиммунным действием |
| US20100087446A1 (en) | 2007-04-26 | 2010-04-08 | Chakravarty Prasun K | 2-substituted indole derivatives as calcium channel blockers |
| MX2009012788A (es) | 2007-05-25 | 2010-01-14 | Medivation Neurology Inc | Metodos y composiciones para estimular celulas. |
| EP2170879B1 (en) | 2007-06-26 | 2013-01-16 | AstraZeneca AB | 1-cyanocyclopropyl-derivatives as cathepsin k inhibitors |
| JP2010535220A (ja) | 2007-08-01 | 2010-11-18 | 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 | 抗精神病用の併用療法剤を使用する統合失調症の治療のための方法および組成物 |
| CA2700160A1 (en) | 2007-09-20 | 2009-03-26 | D2E, Llc | Fluoro-containing derivatives of hydrogenated pyrido[4,3-b]indoles with neuroprotective and cognition enhancing properties, process for preparing, and use |
| 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 |
| WO2009082268A2 (ru) | 2007-12-21 | 2009-07-02 | Alla Chem, Llc | ЛИГАНДЫ α-АДРЕНОЦЕПТОРОВ, ДОПАМИНОВЫХ, ГИСТАМИНОВЫХ, ИМИДАЗОЛИНОВЫХ И СЕРОТОНИНОВЫХ РЕЦЕПТОРОВ И ИХ ПРИМЕНЕНИЕ |
| 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 |
| MX2010010012A (es) | 2008-03-11 | 2010-10-20 | Incyte Corp | 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 |
| PE20091717A1 (es) | 2008-03-24 | 2009-11-25 | Medivation Technologies Inc | Pirido[3,4-b] indoles como moduladores de receptores de histamina |
| TWI450899B (zh) | 2008-03-27 | 2014-09-01 | 被取代之螺環環已烷衍生物 | |
| 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 |
| UY31832A (es) | 2008-05-20 | 2010-01-05 | Astrazeneca Ab | Derivados de indazol sustituidos con fenilo y benzodioxinilo |
| 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 |
| EP2344505A2 (en) | 2008-09-29 | 2011-07-20 | Abbott Laboratories | 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 |
| US20100130528A1 (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 |
| US9962368B2 (en) | 2009-01-09 | 2018-05-08 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| CN102405043B (zh) | 2009-01-09 | 2017-08-22 | 得克萨斯州大学系统董事会 | 前神经原性化合物 |
| AU2010242910B2 (en) | 2009-04-29 | 2015-11-12 | Medivation Technologies, Inc. | Pyrido [4,3-b] indoles and methods of use |
| JP5827943B2 (ja) | 2009-04-29 | 2015-12-02 | 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］インドールおよびその使用方法 |
| 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 |
| CA2775129A1 (en) | 2009-09-23 | 2011-03-31 | Medivation Technologies, Inc. | Pyrido[3,4-b]indoles and methods of use |
| AU2010298166B2 (en) | 2009-09-23 | 2015-09-17 | Medivation Technologies, Inc. | Pyrido[4,3-b]indoles and methods of use |
| CN102724875B (zh) | 2009-09-23 | 2015-05-27 | 梅迪维新技术公司 | 吡啶并[3,4-b]吲哚化合物及其使用方法 |
| CN102711466A (zh) | 2009-09-23 | 2012-10-03 | 梅迪维新技术公司 | 桥连杂环化合物及其使用方法 |
| US9034865B2 (en) | 2010-02-18 | 2015-05-19 | Medivation Technologies, Inc. | Pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use |
| WO2011103487A1 (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 |
| WO2011103460A1 (en) | 2010-02-18 | 2011-08-25 | Medivation Technologies, Inc. | Fused tetracyclic pyrido[4,3-b]indole and pyrido[3,4-b]ondole 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 |
| 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 |
| 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 |
| US9199985B2 (en) | 2011-02-18 | 2015-12-01 | Medivation Technologies, Inc. | Compounds and methods for treatment of hypertension |
| IN2013MN01699A (Direct) | 2011-02-18 | 2015-06-12 | Medivation Technologies Inc | |
| WO2012112961A1 (en) | 2011-02-18 | 2012-08-23 | Medivation Technologies, Inc. | Compounds and methods of treating hypertension |
| 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 |
| WO2014031165A1 (en) | 2012-08-22 | 2014-02-27 | Medivation Technologies, Inc. | Compounds and methods of treating diabetes |
| AU2012388221B2 (en) | 2012-08-24 | 2017-08-31 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
-
2012
- 2012-02-17 IN IN1699MUN2013 patent/IN2013MN01699A/en unknown
- 2012-02-17 CA CA 2829045 patent/CA2829045A1/en not_active Abandoned
- 2012-02-17 CA CA 2827642 patent/CA2827642A1/en not_active Abandoned
- 2012-02-17 CN CN2012800192227A patent/CN103476417A/zh active Pending
- 2012-02-17 JP JP2013554664A patent/JP2014505737A/ja active Pending
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- 2013-03-07 US US13/789,376 patent/US9550782B2/en active Active
- 2013-03-07 US US13/789,361 patent/US9006263B2/en not_active Expired - Fee Related
-
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- 2015-03-06 US US14/641,232 patent/US9527854B2/en not_active Expired - Fee Related
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3484449A (en) * | 1966-05-12 | 1969-12-16 | Hoffmann La Roche | Certain substituted phenyl amino-ethylpyridine intermediates |
| US20100173824A1 (en) * | 2002-05-24 | 2010-07-08 | Exelixis, Inc. | Azepinoindole Derivatives As Pharmaceutical Agents |
| EP2145887A2 (en) * | 2007-04-05 | 2010-01-20 | Alla Chem, LLC. | Substituted 2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indoles, methods for the production and use thereof |
| WO2009005771A1 (en) * | 2007-06-28 | 2009-01-08 | Medivation Neurology, Inc. | A drug demonstrating anxiolytic effect based on hydrogenated pyrido (4, 3-b) indoles, its pharmacological compound and application method |
| WO2010051501A1 (en) * | 2008-10-31 | 2010-05-06 | Medivation Technologies, Inc. | Pyrido (4,3-b) indoles containing rigid moieties |
| US20100152163A1 (en) * | 2008-10-31 | 2010-06-17 | Hung David T | Azepino[4,5-b]indoles and methods of use |
| US20100125085A1 (en) * | 2008-11-17 | 2010-05-20 | Auspex Pharmaceuticals, Inc. | Pyridoindole modulators of nmda receptor and acetylcholinesterase |
| WO2011103448A1 (en) * | 2010-02-19 | 2011-08-25 | Medivation Technologies, Inc. | Methods and compositions for treating psychotic disorders using antipsychotic combination therapy |
Also Published As
| Publication number | Publication date |
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| CN103476416A (zh) | 2013-12-25 |
| JP2014505738A (ja) | 2014-03-06 |
| WO2012154261A1 (en) | 2012-11-15 |
| EP2675459A1 (en) | 2013-12-25 |
| US20140088086A1 (en) | 2014-03-27 |
| US20150266884A1 (en) | 2015-09-24 |
| EP2675459A4 (en) | 2014-08-06 |
| BR112013021126A2 (pt) | 2019-09-24 |
| WO2012112966A1 (en) | 2012-08-23 |
| US9527854B2 (en) | 2016-12-27 |
| CN103476416B (zh) | 2016-09-21 |
| US20130190294A1 (en) | 2013-07-25 |
| EP2675458A4 (en) | 2014-08-06 |
| US8815843B2 (en) | 2014-08-26 |
| US9006263B2 (en) | 2015-04-14 |
| JP2014505737A (ja) | 2014-03-06 |
| CN103476417A (zh) | 2013-12-25 |
| US20130053367A1 (en) | 2013-02-28 |
| US9550782B2 (en) | 2017-01-24 |
| CA2829045A1 (en) | 2012-08-23 |
| BR112013021125A2 (pt) | 2019-09-24 |
| EP2675458A1 (en) | 2013-12-25 |
| US20130053366A1 (en) | 2013-02-28 |
| AU2012219251B2 (en) | 2016-05-12 |
| CA2827642A1 (en) | 2012-11-15 |
| IN2013MN01699A (Direct) | 2015-06-12 |
| US8791132B2 (en) | 2014-07-29 |
| AU2012254158A1 (en) | 2013-05-02 |
| AU2012219251A1 (en) | 2013-05-02 |
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