EA028958B1 - 4-МЕТИЛ-2,3,5,9,9b-ПЕНТААЗАЦИКЛОПЕНТА[a]НАФТАЛИНЫ - Google Patents
4-МЕТИЛ-2,3,5,9,9b-ПЕНТААЗАЦИКЛОПЕНТА[a]НАФТАЛИНЫ Download PDFInfo
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- EA028958B1 EA028958B1 EA201500182A EA201500182A EA028958B1 EA 028958 B1 EA028958 B1 EA 028958B1 EA 201500182 A EA201500182 A EA 201500182A EA 201500182 A EA201500182 A EA 201500182A EA 028958 B1 EA028958 B1 EA 028958B1
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- Eurasian Patent Office
- Prior art keywords
- alkyl
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- those
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Classifications
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Landscapes
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12178713 | 2012-07-31 | ||
| PCT/EP2013/065894 WO2014019979A1 (en) | 2012-07-31 | 2013-07-29 | 4-methyl-2,3,5,9,9b-pentaaza-cyclopenta[a]naphthalenes |
Publications (2)
| Publication Number | Publication Date |
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| EA201500182A1 EA201500182A1 (ru) | 2015-07-30 |
| EA028958B1 true EA028958B1 (ru) | 2018-01-31 |
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| Application Number | Title | Priority Date | Filing Date |
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| EA201500182A EA028958B1 (ru) | 2012-07-31 | 2013-07-29 | 4-МЕТИЛ-2,3,5,9,9b-ПЕНТААЗАЦИКЛОПЕНТА[a]НАФТАЛИНЫ |
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| US9540379B2 (en) | 2011-01-31 | 2017-01-10 | Boehringer Ingelheim International Gmbh | (1,2,4)triazolo[4,3-A]quinoxaline derivatives as inhibitors of phosphodiesterases |
| EP2763989A1 (en) * | 2011-09-09 | 2014-08-13 | H. Lundbeck A/S | Pyridine compounds and uses thereof |
| US20140045856A1 (en) * | 2012-07-31 | 2014-02-13 | Boehringer Ingelheim International Gmbh | 4-Methyl-2,3,5,9,9b-pentaaza-cyclopenta[a]naphthalenes |
| WO2016145614A1 (en) | 2015-03-17 | 2016-09-22 | Merck Sharp & Dohme Corp. | Triazolyl pyrimidinone compounds as pde2 inhibitors |
| WO2016154081A1 (en) | 2015-03-26 | 2016-09-29 | Merck Sharp & Dohme Corp. | Pyrazolyl pyrimidinone compounds as pde2 inhibitors |
| WO2016179059A1 (en) | 2015-05-05 | 2016-11-10 | Merck Sharp & Dohme Corp. | Heteroaryl-pyrimidinone compounds as pde2 inhibitors |
| WO2016183741A1 (en) | 2015-05-15 | 2016-11-24 | Merck Sharp & Dohme Corp. | Pyrimidinone amide compounds as pde2 inhibitors |
| US10618898B2 (en) * | 2015-05-20 | 2020-04-14 | Guangdong Raynovent Biotech Co., Ltd. | Hydroxyl purine compounds and use thereof |
| WO2016191935A1 (en) | 2015-05-29 | 2016-12-08 | Merck Sharp & Dohme Corp. | 6-alkyl dihydropyrazolopyrimidinone compounds as pde2 inhibitors |
| WO2016192083A1 (en) | 2015-06-04 | 2016-12-08 | Merck Sharp & Dohme Corp. | Dihydropyrazolopyrimidinone compounds as pde2 inhibitors |
| WO2016209749A1 (en) | 2015-06-25 | 2016-12-29 | Merck Sharp & Dohme Corp. | Substituted pyrazolo/imidazolo bicyclic compounds as pde2 inhibitors |
| WO2017000276A1 (en) | 2015-07-01 | 2017-01-05 | Merck Sharp & Dohme Corp. | Bicyclic heterocyclic compounds as pde2 inhibitors |
| WO2017000277A1 (en) | 2015-07-01 | 2017-01-05 | Merck Sharp & Dohme Corp. | Substituted triazolo bicycliccompounds as pde2 inhibitors |
| EP3156405A1 (en) * | 2015-10-13 | 2017-04-19 | Boehringer Ingelheim International GmbH | Spirocyclic ether derivatives of pyrazolo[1,5-a]pyrimidine-3-carboxamide |
| WO2017176652A2 (en) | 2016-04-04 | 2017-10-12 | Sinopia Biosciences, Inc. | Treating extrapyramidal syndrome using trapidil |
| AR112457A1 (es) * | 2017-08-02 | 2019-10-30 | Lilly Co Eli | Derivados de [1,2,4]triazolo[4,3-a]pirazin-6(5h)-ona |
| PL3713572T3 (pl) | 2017-11-23 | 2025-09-22 | Oslo University Hospital Hf | Leczenie tachykardii |
| CN115960101B (zh) * | 2022-12-30 | 2024-10-18 | 海南大学 | 7-氧代-4,5,6,7-四氢吡唑并吡啶酰胺类化合物及其制备方法和应用 |
Citations (5)
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| WO2007137819A1 (en) * | 2006-05-30 | 2007-12-06 | Elbion Gmbh | 4-AMINO-PYRIDO[3,2-e]PYRAZINES, THEIR USE AS INHIBITORS OF PHOSPHODIESTERASE 10, AND PROCESSES FOR PREPARING THEM |
| WO2007137820A1 (en) * | 2006-05-30 | 2007-12-06 | Elbion Gmbh | PYRIDO[3,2-e]PYRAZINES, THEIR USE AS INHIBITORS OF PHOSPHODIESTERASE 10, AND PROCESSES FOR PREPARING THEM |
| WO2010054253A1 (en) * | 2008-11-07 | 2010-05-14 | Biotie Therapies Gmbh | Triazine derivatives as inhibitors of phosphodiesterases |
| US20120178748A1 (en) * | 2011-01-11 | 2012-07-12 | Sunovion Pharmaceuticals Inc. | Heteroaryl compounds and methods of use thereof |
| WO2013034761A1 (en) * | 2011-09-09 | 2013-03-14 | H. Lundbeck A/S | Pyridine compounds and uses thereof |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000319278A (ja) * | 1999-05-11 | 2000-11-21 | Ono Pharmaceut Co Ltd | 縮合ピラジン化合物およびその化合物を有効成分とする薬剤 |
| JP2000319277A (ja) * | 1999-05-11 | 2000-11-21 | Ono Pharmaceut Co Ltd | 縮合ピラジン化合物およびその化合物を有効成分とする薬剤 |
| DE10108752A1 (de) | 2001-02-23 | 2002-09-05 | Bayer Ag | Neue Substituierte Imidazotriazinone |
| WO2004085439A1 (en) | 2003-03-27 | 2004-10-07 | Pfizer Products Inc. | Substituted 4-amino[1,2,4]triazolo[4,3-a]quinoxalines |
| WO2005041957A1 (en) | 2003-10-29 | 2005-05-12 | Pfizer Products Inc. | Oxindole derivatives and their use as phosphodiesterase type 2 inhibitors |
| AP2006003632A0 (en) | 2003-12-16 | 2006-06-30 | Pfizer Prod Inc | Pyridol[2,3-D] pyrimidine-2,4-Diamines as PDE 2 inhibitors |
| EP1548011A1 (en) | 2003-12-23 | 2005-06-29 | Neuro3D | Benzo[1,4]diazepin-2-one derivatives as phosphodiesterase PDE2 inhibitors, preparation and therapeutic use thereof |
| FR2865331A1 (fr) | 2004-01-21 | 2005-07-22 | France Telecom | Procede de connexion d'un reseau domestique a un serveur cops distant et dispositif associe |
| FR2870539B1 (fr) | 2004-05-19 | 2006-08-04 | Greenpharma Sa Sa | Nouvelles methodes et medicaments |
| DE602005021894D1 (de) | 2004-09-02 | 2010-07-29 | Nycomed Gmbh | Triazolophthalazine |
| EP1874775B1 (en) | 2005-01-05 | 2012-10-10 | Nycomed GmbH | Triazolophthalazines as pde2-inhibitors |
| KR20070095986A (ko) | 2005-01-05 | 2007-10-01 | 니코메드 게엠베하 | Ｐｄｅ2 억제제로서의 트리아졸로프탈라진 |
| BRPI0502411A (pt) | 2005-03-31 | 2006-11-28 | Univ Minas Gerais | processo de desenvolvimento de substáncias como inibidores potentes e seletivos de isoformas de fosfodiesterases dos tipos 1 a 5 (pde1,pde2,pde3, pde4, pde5) na base de diocleìna, fluranol ou análogos e suas composições farmacêuticas para o estudo e tratamento de doenças cardiovasculares e produtos associados |
| JP2009523820A (ja) | 2006-01-23 | 2009-06-25 | アミラ ファーマシューティカルス，インコーポレーテッド | ５−リポキシゲナーゼの三環系抑制剤 |
| WO2007121319A2 (en) | 2006-04-14 | 2007-10-25 | University Of California | Compostions and methods for determining and predicting treatment responses for depression and anxiety |
| US20080090834A1 (en) | 2006-07-06 | 2008-04-17 | Pfizer Inc | Selective azole pde10a inhibitor compounds |
| DE102006048693A1 (de) | 2006-10-14 | 2008-04-17 | Bayer Healthcare Ag | Inhibition der PDE2A |
| WO2008072779A1 (ja) * | 2006-12-13 | 2008-06-19 | Aska Pharmaceutical Co., Ltd. | キノキサリン誘導体 |
| US20090143361A1 (en) * | 2007-11-30 | 2009-06-04 | Elbion Gmbh | Pyrido[3,2-E]Pyrazines, Process For Preparing The Same, And Their Use As Inhibitors Of Phosphodiesterase 10 |
| TWI501965B (zh) | 2008-06-20 | 2015-10-01 | Lundbeck & Co As H | 作為ｐｄｅ１０ａ酵素抑制劑之新穎苯基咪唑衍生物 |
| KR20110095857A (ko) | 2008-09-10 | 2011-08-25 | 칼립시스, 인코포레이티드 | 질환의 치료를 위한 히스타민 수용체의 헤테로시클릭 억제제 |
| EP2346873A1 (en) | 2008-10-08 | 2011-07-27 | Bristol-Myers Squibb Company | Azolopyrrolone melanin concentrating hormone receptor-1 antagonists |
| WO2010104933A1 (en) * | 2009-03-11 | 2010-09-16 | Merck Sharp & Dohme Corp. | Inhibitors of akt activity |
| EP2266985A1 (en) * | 2009-06-26 | 2010-12-29 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Tricyclic Pyrimidine Derivatives as Wnt antagonists |
| US9540379B2 (en) | 2011-01-31 | 2017-01-10 | Boehringer Ingelheim International Gmbh | (1,2,4)triazolo[4,3-A]quinoxaline derivatives as inhibitors of phosphodiesterases |
| WO2013000924A1 (en) | 2011-06-27 | 2013-01-03 | Janssen Pharmaceutica Nv | 1-ARYL-4-METHYL-[1,2,4]TRIAZOLO[4,3-a]QUINOXALINE DERIVATIVES |
| WO2013034758A1 (en) | 2011-09-09 | 2013-03-14 | H. Lundbeck A/S | Substituted triazolopyrazines and uses thereof |
| AR088082A1 (es) | 2011-10-13 | 2014-05-07 | Lilly Co Eli | Moduladores selectivos del receptor androgeno |
| WO2014001314A1 (en) | 2012-06-26 | 2014-01-03 | Janssen Pharmaceutica Nv | Combinations comprising pde 2 inhibitors such as 1-aryl-4-methyl- [1,2,4] triazolo [4,3-a] quinoxaline compounds and pde 10 inhibitors for use in the treatment of neurological or metabolic disorders |
| US20140045856A1 (en) * | 2012-07-31 | 2014-02-13 | Boehringer Ingelheim International Gmbh | 4-Methyl-2,3,5,9,9b-pentaaza-cyclopenta[a]naphthalenes |
-
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007137819A1 (en) * | 2006-05-30 | 2007-12-06 | Elbion Gmbh | 4-AMINO-PYRIDO[3,2-e]PYRAZINES, THEIR USE AS INHIBITORS OF PHOSPHODIESTERASE 10, AND PROCESSES FOR PREPARING THEM |
| WO2007137820A1 (en) * | 2006-05-30 | 2007-12-06 | Elbion Gmbh | PYRIDO[3,2-e]PYRAZINES, THEIR USE AS INHIBITORS OF PHOSPHODIESTERASE 10, AND PROCESSES FOR PREPARING THEM |
| WO2010054253A1 (en) * | 2008-11-07 | 2010-05-14 | Biotie Therapies Gmbh | Triazine derivatives as inhibitors of phosphodiesterases |
| US20120178748A1 (en) * | 2011-01-11 | 2012-07-12 | Sunovion Pharmaceuticals Inc. | Heteroaryl compounds and methods of use thereof |
| WO2013034761A1 (en) * | 2011-09-09 | 2013-03-14 | H. Lundbeck A/S | Pyridine compounds and uses thereof |
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