JP2011500855A5 - - Google Patents
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- JP2011500855A5 JP2011500855A5 JP2010531322A JP2010531322A JP2011500855A5 JP 2011500855 A5 JP2011500855 A5 JP 2011500855A5 JP 2010531322 A JP2010531322 A JP 2010531322A JP 2010531322 A JP2010531322 A JP 2010531322A JP 2011500855 A5 JP2011500855 A5 JP 2011500855A5
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| EP2424364A4 (en) * | 2009-04-29 | 2012-12-19 | Medivation Technologies Inc | PYRIDO [4.3-B] INDOLES AND METHODS OF USE |
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| US20130137705A1 (en) * | 2009-09-23 | 2013-05-30 | Sarvajit Chakravarty | Pyrido[3,4-b]indoles and methods of use |
| US8575186B2 (en) | 2009-10-05 | 2013-11-05 | Albany Molecular Research, Inc. | Epiminocycloalkyl[b] indole derivatives as serotonin sub-type 6 (5-HT6) modulators and uses thereof |
| WO2011047374A1 (en) * | 2009-10-18 | 2011-04-21 | Mount Sinai School Of Medicine Of New York University | Methods of treating tauopathies |
| 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 |
| US9040519B2 (en) | 2010-02-18 | 2015-05-26 | 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 |
| 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 |
| WO2011103448A1 (en) * | 2010-02-19 | 2011-08-25 | Medivation Technologies, Inc. | Methods and compositions for treating psychotic disorders using antipsychotic combination therapy |
| WO2011103430A1 (en) * | 2010-02-19 | 2011-08-25 | Medivation Technologies, Inc. | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| JP2013522376A (ja) * | 2010-03-24 | 2013-06-13 | メディカル ユニバーシティー オブ サウス カロライナ | 変性疾患を治療するための組成物および方法 |
| CA2804161A1 (en) | 2010-07-07 | 2012-01-12 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| WO2012099952A2 (en) | 2011-01-19 | 2012-07-26 | Albany Molecular Research, Inc. | Benzofuro[3,2-c] pyridines and related analogs as serotonin sub-type 6 (5-ht6) modulators for the treatment of obesity, metabolic syndrome, cognition and schizophrenia |
| WO2012154261A1 (en) * | 2011-02-18 | 2012-11-15 | Medivation Technologies, Inc. | Compounds and methods of treating diabetes |
| US9199985B2 (en) | 2011-02-18 | 2015-12-01 | Medivation Technologies, Inc. | Compounds and methods for treatment of 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 |
| US9434747B2 (en) | 2011-02-18 | 2016-09-06 | Medivation Technologies, Inc. | Methods of treating diabetes |
| ES2587856T3 (es) | 2011-03-18 | 2016-10-27 | Ono Pharmaceutical Co., Ltd. | Derivado de tetrahidrocarbolina |
| RU2490268C2 (ru) * | 2011-11-10 | 2013-08-20 | Федеральное Государственное Бюджетное Учреждение Науки Институт Физиологически Активных Веществ Российской Академии Наук (Ифав Ран) | ХЛОРГИДРАТЫ ФТОРСОДЕРЖАЩИХ ЗАМЕЩЕННЫХ 5-[2-(ПИРИД-3-ИЛ)-ЭТИЛ]-2,3,4,5-ТЕТРАГИДРО-1Н-ПИРИДО[4,3-b]ИНДОЛОВ, В КАЧЕСТВЕ СРЕДСТВ СНИЖЕНИЯ НЕКОНТРОЛИРУЕМОЙ АГРЕГАЦИИ БЕЛКОВ В НЕРВНОЙ СИСТЕМЕ, ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ИХ ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| UA125503C2 (uk) | 2012-06-13 | 2022-04-13 | Інсайт Холдинґс Корпорейшн | Заміщені трициклічні сполуки як інгібітори fgfr |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| CA2882826A1 (en) | 2012-08-24 | 2014-02-27 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| MY181497A (en) | 2013-04-19 | 2020-12-23 | Incyte Holdings Corp | Bicyclic heterocycles as fgfr inhibitors |
| WO2014207241A1 (en) * | 2013-06-28 | 2014-12-31 | Alzprotect | NEW Na-SUBSTITUTED CARBOLINE COMPOUNDS USABLE FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES |
| WO2015070237A1 (en) | 2013-11-11 | 2015-05-14 | Board Of Regents Of The University Of Texas System | Neuroprotective chemicals and methods for identifying and using same |
| US9902713B2 (en) | 2013-11-11 | 2018-02-27 | Board Of Regents Of The University Of Texas System | Neuroprotective compounds and use thereof |
| US10092550B2 (en) | 2014-10-21 | 2018-10-09 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions containing curcumin, harmine, and isovanillin components, and methods of use thereof |
| US9907786B2 (en) | 2014-10-21 | 2018-03-06 | Ions Pharmaceutical S.À R.L. | Therapeutic compositions containing harmine and isovanillin components, and methods of use thereof |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| CR20170390A (es) | 2015-02-20 | 2017-10-23 | Incyte Holdings Corp | Heterociclos biciclicos como inhibidores de fgfr |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| US9580423B2 (en) | 2015-02-20 | 2017-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| CN104829614B (zh) * | 2015-04-17 | 2020-04-28 | 河南师范大学 | 一种合成4氢-吡咯[3,2-c]吡啶-4-酮类化合物的方法 |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| MX2020008237A (es) | 2018-02-05 | 2020-09-25 | Univ Rockefeller | Inhibidores de 2,3,4,5-tetrahidro-1h-pirido[4,3-b]indol de cgas para tratar enfermedades autoinflamatorias. |
| PE20210919A1 (es) | 2018-05-04 | 2021-05-19 | Incyte Corp | Sales de un inhibidor de fgfr |
| BR112020022392A2 (pt) | 2018-05-04 | 2021-02-02 | Incyte Corporation | formas sólidas de um inibidor de fgfr e processos para preparação das mesmas |
| BR112021016620A2 (pt) * | 2019-02-27 | 2021-11-03 | Univ California | Azepino-indóis e outros heterociclos para o tratamento de distúrbios cerebrais |
| US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
| CN114901279A (zh) * | 2019-03-13 | 2022-08-12 | 洛克菲勒大学 | 用于治疗自身炎性疾病和癌症转移的cGAS的抑制剂 |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| US12122767B2 (en) | 2019-10-01 | 2024-10-22 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| GEP20247679B (en) | 2019-10-14 | 2024-10-10 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| WO2021076728A1 (en) | 2019-10-16 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| JP7720840B2 (ja) | 2019-12-04 | 2025-08-08 | インサイト・コーポレイション | Fgfr阻害剤としての三環式複素環 |
| PE20221504A1 (es) | 2019-12-04 | 2022-09-30 | Incyte Corp | Derivados de un inhibidor de fgfr |
| WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| EA202191320A1 (ru) * | 2020-03-19 | 2021-10-22 | Андрей Александрович ИВАЩЕНКО | Норадренергический и специфически серотонинергический анксиолитик и антидепрессант, способ его получения и применения |
| JP2023530664A (ja) * | 2020-06-10 | 2023-07-19 | デリックス セラピューティクス,インク. | 三環系サイコプラストゲンおよびその使用 |
| US12129265B2 (en) | 2020-07-21 | 2024-10-29 | Ankh Life Sciences Limited | Therapeutic agents and uses thereof |
| TW202304459A (zh) | 2021-04-12 | 2023-02-01 | 美商英塞特公司 | 包含fgfr抑制劑及nectin-4靶向劑之組合療法 |
| TW202313611A (zh) | 2021-06-09 | 2023-04-01 | 美商英塞特公司 | 作為fgfr抑制劑之三環雜環 |
| CA3220155A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| CA3239565A1 (en) | 2021-12-15 | 2023-06-22 | Delix Therapeutics, Inc. | Phenoxy and benzyloxy substituted psychoplastogens and uses thereof |
| CN117186089A (zh) * | 2023-07-07 | 2023-12-08 | 浙江大学 | 一种四氢咔啉衍生物的制备方法 |
Family Cites Families (69)
| 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 |
| US3409628A (en) * | 1966-05-12 | 1968-11-05 | Hoffmann La Roche | 5-(3-pyridylethyl)pyridoindole 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 |
| JPS5143863B2 (enExample) * | 1973-06-18 | 1976-11-25 | ||
| US4754038A (en) | 1987-02-26 | 1988-06-28 | American Home Products Corporation | Carboline histamine H1 antagonists |
| NZ230154A (en) | 1988-08-02 | 1991-10-25 | Glaxo Group Ltd | Imidazolyl-substituted 6- or 7-membered ring lactam derivatives and pharmaceutical composition |
| 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 |
| DE10030375A1 (de) * | 2000-06-21 | 2002-01-03 | Bayer Ag | Verwendung von MTP-Inhibitoren zur Senkung von ppTRL |
| 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 |
| US7736889B2 (en) | 2003-06-10 | 2010-06-15 | The United States Of America As Represented By The Secretary Of The Navy | Fluidic force discrimination |
| 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 |
| AU2005315319B2 (en) * | 2004-12-17 | 2011-07-07 | Glenmark Pharmaceuticals S.A. | Novel heterocyclic compounds useful for the treatment of inflammatory and allergic disorders |
| EA200800430A1 (ru) | 2005-07-28 | 2008-06-30 | Бристол-Маерс Сквибб Компани | Замещённые тетрагидро-1н-пиридо[4,3,b] индолы как агонисты и антагонисты серотониновых рецепторов |
| 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 |
| US20100152225A1 (en) | 2006-09-20 | 2010-06-17 | David Hung | Hydrogenated pyrido [4,3-b] indoles such as dimebon for treating canine cognitive dysfunction syndrome |
| CA2664099A1 (en) | 2006-09-20 | 2008-03-27 | Medivation Neurology, Inc. | Methods and compositions for treating amyotrophic lateral sclerosis (als) |
| AU2007309390A1 (en) | 2006-10-27 | 2008-05-02 | Medivation Neurology, Inc. | Methods and combination therapies for treating Alzheimer's disease |
| 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 |
| 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 |
| AU2008257152A1 (en) | 2007-05-25 | 2008-12-04 | Medivation Neurology, Inc. | Methods and compositions for stimulating cells |
| 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 |
| 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 |
| JP2010540439A (ja) * | 2007-09-20 | 2010-12-24 | ディー2イー,エルエルシー | 神経保護性の及び認知を向上させる性質を備えた水素化されたピリド[4,3−b]インドール類のフッ素を含有する誘導体、調製するための工程、並びに使用 |
| 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 |
| JP2011507835A (ja) | 2007-12-21 | 2011-03-10 | アンドレイ・アレクサンドロビッチ・イワシェンコ | α−アドレナリン受容体、ドーパミン、ヒスタミン、イミダゾリン及びセロトニン受容体のリガンド並びにその使用 |
| 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 |
| PE20091820A1 (es) * | 2008-03-24 | 2009-12-10 | Medivation Technologies Inc | Compuestos heterociclicos con uniones puente y metodos para usarlos |
| EP2280968A2 (en) | 2008-03-24 | 2011-02-09 | Medivation Technologies, Inc. | Pyrido [3, 4-b]indoles and methods of use |
| 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 |
| 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 |
| JP2012504137A (ja) | 2008-09-29 | 2012-02-16 | アボット・ラボラトリーズ | インドール誘導体およびインドリン誘導体ならびにそれらの使用方法 |
| US9625475B2 (en) | 2008-09-29 | 2017-04-18 | Abbvie Inc. | Indole and indoline derivatives and methods of use thereof |
| US8907097B2 (en) | 2008-10-31 | 2014-12-09 | 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 |
| US9962368B2 (en) | 2009-01-09 | 2018-05-08 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| US8604074B2 (en) | 2009-01-09 | 2013-12-10 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| US8362277B2 (en) | 2009-01-09 | 2013-01-29 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| US20100215814A1 (en) * | 2009-02-23 | 2010-08-26 | Sam Freitas | Premixed bloody mary with alcohol |
| EP2424364A4 (en) * | 2009-04-29 | 2012-12-19 | Medivation Technologies Inc | PYRIDO [4.3-B] INDOLES AND METHODS OF USE |
| US8741919B2 (en) * | 2009-04-29 | 2014-06-03 | 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 |
| 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 |
| BR112012006648A2 (pt) | 2009-09-23 | 2019-09-24 | Medivation Neurology Inc | composto,método de tratamento de um distúrbio cognitivo, distúrbio psicótico, distúrbio mediado por neurotransmissor ou um distúrbio neuronal, composição farmacêutica e kit |
| CA2775328A1 (en) | 2009-09-23 | 2011-03-31 | Medivation Technologies, Inc. | Pyrido[4,3-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 |
| WO2011038163A1 (en) | 2009-09-23 | 2011-03-31 | Medivation Technologies, Inc. | Pyrido[3,4-b]indoles 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 |
| US9040519B2 (en) | 2010-02-18 | 2015-05-26 | Medivation Technologies, Inc. | Fused tetracyclic 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 |
| WO2011103430A1 (en) | 2010-02-19 | 2011-08-25 | 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 |
| CA2804161A1 (en) | 2010-07-07 | 2012-01-12 | Board Of Regents Of The University Of Texas System | Pro-neurogenic compounds |
| 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 |
| WO2012154261A1 (en) | 2011-02-18 | 2012-11-15 | Medivation Technologies, Inc. | Compounds and methods of treating diabetes |
| US9434747B2 (en) | 2011-02-18 | 2016-09-06 | Medivation Technologies, Inc. | Methods of treating diabetes |
| US9199985B2 (en) | 2011-02-18 | 2015-12-01 | Medivation Technologies, Inc. | Compounds and methods for treatment of 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 |
| EP2887805A4 (en) | 2012-08-22 | 2016-08-17 | Medivation Technologies Inc | COMPOUNDS AND METHOD FOR TREATING BLOOD HIGH PRESSURE |
| CN108329253A (zh) | 2012-08-24 | 2018-07-27 | 得克萨斯州大学系统董事会 | 前神经原性化合物 |
-
2007
- 2007-10-25 RU RU2007139634/04A patent/RU2007139634A/ru not_active Application Discontinuation
-
2008
- 2008-10-27 US US12/259,234 patent/US8338408B2/en not_active Expired - Fee Related
- 2008-10-27 JP JP2010531322A patent/JP5665543B2/ja not_active Expired - Fee Related
- 2008-10-27 CN CN2008801226525A patent/CN101952284A/zh active Pending
- 2008-10-27 WO PCT/US2008/081390 patent/WO2009055828A1/en not_active Ceased
- 2008-10-27 CN CN201610525730.2A patent/CN106188043A/zh active Pending
- 2008-10-27 UY UY31436A patent/UY31436A1/es not_active Application Discontinuation
- 2008-10-27 CA CA2704008A patent/CA2704008A1/en not_active Abandoned
- 2008-10-27 BR BRPI0816582-3A patent/BRPI0816582A2/pt not_active IP Right Cessation
- 2008-10-27 PE PE2008001834A patent/PE20091346A1/es not_active Application Discontinuation
- 2008-10-27 AU AU2008316560A patent/AU2008316560B2/en not_active Ceased
- 2008-10-27 EP EP08841761A patent/EP2217598A1/en not_active Withdrawn
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2012
- 2012-11-16 US US13/679,873 patent/US8999978B2/en not_active Expired - Fee Related
- 2012-12-21 US US13/725,909 patent/US9181240B2/en not_active Expired - Fee Related
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2013
- 2013-03-08 US US13/791,750 patent/US9034880B2/en not_active Expired - Fee Related
- 2013-03-12 US US13/797,723 patent/US9096591B2/en not_active Expired - Fee Related
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2015
- 2015-02-25 US US14/631,615 patent/US20150182509A1/en not_active Abandoned
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