CN102131801B - 1,2-二取代的杂环化合物 - Google Patents
1,2-二取代的杂环化合物 Download PDFInfo
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- CN102131801B CN102131801B CN200980133288.7A CN200980133288A CN102131801B CN 102131801 B CN102131801 B CN 102131801B CN 200980133288 A CN200980133288 A CN 200980133288A CN 102131801 B CN102131801 B CN 102131801B
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- Prior art keywords
- phenyl
- water
- dimethyl
- ylmethoxy
- quinolin
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- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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Applications Claiming Priority (9)
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| US7559408P | 2008-06-25 | 2008-06-25 | |
| US61/075,594 | 2008-06-25 | ||
| US10916208P | 2008-10-28 | 2008-10-28 | |
| US61/109,162 | 2008-10-28 | ||
| US13886608P | 2008-12-18 | 2008-12-18 | |
| US61/138,866 | 2008-12-18 | ||
| US17641309P | 2009-05-07 | 2009-05-07 | |
| US61/176,413 | 2009-05-07 | ||
| PCT/US2009/048426 WO2009158393A1 (en) | 2008-06-25 | 2009-06-24 | 1, 2 disubstituted heterocyclic compounds |
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| CN102131801A CN102131801A (zh) | 2011-07-20 |
| CN102131801B true CN102131801B (zh) | 2015-04-08 |
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| CN200980133288.7A Expired - Fee Related CN102131801B (zh) | 2008-06-25 | 2009-06-24 | 1,2-二取代的杂环化合物 |
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|---|---|---|---|---|
| EP2296653B1 (en) | 2008-06-03 | 2016-01-27 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| CN102131801B (zh) | 2008-06-25 | 2015-04-08 | 福拉姆医药股份有限公司 | 1,2-二取代的杂环化合物 |
| PL2617420T3 (pl) * | 2009-05-07 | 2016-04-29 | Forum Pharmaceuticals Inc | Heterocykliczne związki fenoksymetylu |
| SG176105A1 (en) | 2009-06-26 | 2011-12-29 | Novartis Ag | 1, 3-disubstituted imidazolidin-2-one derivatives as inhibitors of cyp 17 |
| JP5785548B2 (ja) | 2010-08-04 | 2015-09-30 | 武田薬品工業株式会社 | 縮合複素環化合物 |
| JP5760085B2 (ja) * | 2010-08-04 | 2015-08-05 | 武田薬品工業株式会社 | 縮合複素環化合物 |
| DK2619208T3 (en) | 2010-09-20 | 2017-01-30 | Ironwood Pharmaceuticals Inc | IMIDAZOTRIAZINON COMPOUNDS |
| CA2824047C (en) | 2011-01-11 | 2019-06-18 | Sunovion Pharmaceuticals Inc. | Heteroaryl compounds and methods of use thereof |
| MX2013009575A (es) | 2011-02-18 | 2014-10-14 | Exonhit Therapeutics Sa | Derivados de 6, 7-dialcoxi-3-isoquinolinol sustituidos como inhibidores de fosfodiesterasa 10 (pdei0a). |
| US9029399B2 (en) | 2011-04-28 | 2015-05-12 | Novartis Ag | 17α-hydroxylase/C17,20-lyase inhibitors |
| WO2013047411A1 (ja) * | 2011-09-29 | 2013-04-04 | 富士フイルム株式会社 | 新規なトリアジン誘導体、紫外線吸収剤 |
| HK1206726A1 (en) | 2012-03-19 | 2016-01-15 | Ironwood Pharmaceuticals, Inc. | Imidazotriazinone compounds |
| EP2858982A4 (en) | 2012-06-12 | 2015-11-11 | Abbvie Inc | PYRIDINONE AND PYRIDAZINONE DERIVATIVES |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| WO2014071044A1 (en) | 2012-11-01 | 2014-05-08 | Allergan, Inc. | Substituted 6,7-dialkoxy-3-isoquinoline derivatives as inhibitors of phosphodiesterase 10 (pde10a) |
| TW201512201A (zh) * | 2013-03-14 | 2015-04-01 | Forum Pharmaceuticals Inc | 化合物的多晶型及鹽類 |
| WO2014142322A1 (ja) | 2013-03-15 | 2014-09-18 | 第一三共株式会社 | ベンゾチオフェン誘導体 |
| TWI634114B (zh) * | 2013-05-08 | 2018-09-01 | 永恒生物科技公司 | 作為激酶抑制劑之呋喃酮化合物 |
| DK3013813T3 (da) | 2013-06-27 | 2019-06-03 | Pfizer | Heteroaromatiske forbindelser og anvendelse deraf som dopamin-d1-ligander |
| WO2015006689A1 (en) | 2013-07-12 | 2015-01-15 | University Of South Alabama | Treatment and diagnosis of cancer and precancerous conditions using pde10a inhibitors and methods to measure pde10a expression |
| US9200016B2 (en) | 2013-12-05 | 2015-12-01 | Allergan, Inc. | Substituted 6, 7-dialkoxy-3-isoquinoline derivatives as inhibitors of phosphodiesterase 10 (PDE 10A) |
| RU2692485C2 (ru) | 2014-04-02 | 2019-06-25 | Интермьюн, Инк. | Противофиброзные пиридиноны |
| CN104211638A (zh) * | 2014-08-13 | 2014-12-17 | 李增 | 一种脂肪氨基取代的芸香碱类衍生物及其制备和作为抗阿尔兹海默症的药物中的应用 |
| CN104610134B (zh) * | 2015-01-29 | 2017-01-25 | 安徽星宇化工有限公司 | 一种6‑甲基‑2‑吡啶基甲醇的制备方法 |
| US10738035B2 (en) | 2015-05-13 | 2020-08-11 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| WO2017011552A1 (en) * | 2015-07-13 | 2017-01-19 | Enanta Pharmaceuticals, Inc. | Hepatitis b antiviral agents |
| CN109069488B (zh) | 2016-03-07 | 2021-09-07 | 英安塔制药有限公司 | 乙型肝炎抗病毒剂 |
| JP2020512400A (ja) * | 2017-03-23 | 2020-04-23 | クラヴィウス ファーマシューティカルズ,エルエルシー | TGFβの阻害のための三置換イミダゾールおよび治療方法 |
| TWI788343B (zh) * | 2017-04-18 | 2023-01-01 | 美商塞爾基因定量細胞研究公司 | 治療用化合物 |
| TWI811236B (zh) | 2017-08-28 | 2023-08-11 | 美商因那塔製藥公司 | B型肝炎抗病毒試劑 |
| WO2019143902A2 (en) | 2018-01-22 | 2019-07-25 | Enanta Pharmaceuticals, Inc. | Substituted heterocycles as antiviral agents |
| WO2019191166A1 (en) | 2018-03-29 | 2019-10-03 | Enanta Pharmaceuticals, Inc. | Hepatitis b antiviral agents |
| EP3840748A4 (en) | 2018-08-22 | 2022-06-29 | Clavius Pharmaceuticals, LLC | Substituted imidazoles for the inhibition of tgf-beta and methods of treatment |
| US10865211B2 (en) | 2018-09-21 | 2020-12-15 | Enanta Pharmaceuticals, Inc. | Functionalized heterocycles as antiviral agents |
| US11198693B2 (en) | 2018-11-21 | 2021-12-14 | Enanta Pharmaceuticals, Inc. | Functionalized heterocycles as antiviral agents |
| EP3886854A4 (en) | 2018-11-30 | 2022-07-06 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| US11236111B2 (en) | 2019-06-03 | 2022-02-01 | Enanta Pharmaceuticals, Inc. | Hepatitis B antiviral agents |
| WO2020247561A1 (en) | 2019-06-04 | 2020-12-10 | Enanta Pharmaceuticals, Inc, | Hepatitis b antiviral agents |
| US11472808B2 (en) | 2019-06-04 | 2022-10-18 | Enanta Pharmaceuticals, Inc. | Substituted pyrrolo[1,2-c]pyrimidines as hepatitis B antiviral agents |
| US11738019B2 (en) | 2019-07-11 | 2023-08-29 | Enanta Pharmaceuticals, Inc. | Substituted heterocycles as antiviral agents |
| US11236108B2 (en) | 2019-09-17 | 2022-02-01 | Enanta Pharmaceuticals, Inc. | Functionalized heterocycles as antiviral agents |
| KR102811543B1 (ko) | 2019-10-16 | 2025-05-23 | 삼성디스플레이 주식회사 | 유기 전계 발광 소자 및 유기 전계 발광 소자용 다환 화합물 |
| US11802125B2 (en) | 2020-03-16 | 2023-10-31 | Enanta Pharmaceuticals, Inc. | Functionalized heterocyclic compounds as antiviral agents |
| WO2023059224A1 (en) | 2021-10-09 | 2023-04-13 | Joint Stock Company "Pharmasyntez" | A new class of antiviral drugs |
| KR20250110929A (ko) | 2022-12-02 | 2025-07-21 | 뉴모라 테라퓨틱스, 인코포레이티드 | 신경학적 장애를 치료하는 방법 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006072828A2 (en) * | 2005-01-07 | 2006-07-13 | Pfizer Products Inc. | Heteroaromatic quinoline compounds and their use as pde10 inhibitors |
| WO2007077490A2 (en) * | 2006-01-05 | 2007-07-12 | Pfizer Products Inc. | Bicyclic heteroaryl compounds as pde10 inhibitors |
| WO2007129183A2 (en) * | 2006-05-02 | 2007-11-15 | Pfizer Products Inc. | Bicyclic heteroaryl compounds as pde10 inhibitors |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE284885T1 (de) * | 2000-07-27 | 2005-01-15 | Hoffmann La Roche | 3-indolyl-4-phenyl-1h-pyrrol-2,5-dion derivate als glycogen synthase kinase 3beta inhibitoren |
| US20030032579A1 (en) | 2001-04-20 | 2003-02-13 | Pfizer Inc. | Therapeutic use of selective PDE10 inhibitors |
| JPWO2004002484A1 (ja) | 2002-06-26 | 2005-10-27 | 協和醗酵工業株式会社 | ホスホジエステラーゼ阻害剤 |
| JP2007145819A (ja) * | 2005-10-28 | 2007-06-14 | Tanabe Seiyaku Co Ltd | 医薬組成物 |
| EP1845098A1 (en) | 2006-03-29 | 2007-10-17 | Ferrer Internacional, S.A. | Imidazo[1,2-b]pyridazines, their processes of preparation and their use as GABA receptor ligands |
| WO2008033455A2 (en) | 2006-09-13 | 2008-03-20 | The Institutes For Pharmaceutical Discovery, Llc | Biphenyl and heteroaryl phenyl derivatives as protein tyrosine phosphatases inhibitors |
| AU2007312391B2 (en) * | 2006-10-19 | 2012-06-21 | F. Hoffmann-La Roche Ag | Imidazolone and imidazolidinone derivatives as 11b-HSD1 inhibitors for diabetes |
| FR2928924B1 (fr) | 2008-03-21 | 2010-04-23 | Sanofi Aventis | Derives polysubstitues de 6-heteroaryle-imidazo°1,2-a! pyridines, leur preparation et leur application en therapeutique |
| CN102131801B (zh) | 2008-06-25 | 2015-04-08 | 福拉姆医药股份有限公司 | 1,2-二取代的杂环化合物 |
| PL2617420T3 (pl) | 2009-05-07 | 2016-04-29 | Forum Pharmaceuticals Inc | Heterocykliczne związki fenoksymetylu |
| JP5868855B2 (ja) | 2009-09-03 | 2016-02-24 | アラーガン、インコーポレイテッドAllergan,Incorporated | チロシンキナーゼ調節剤としての化合物 |
| SI3311666T1 (sl) | 2010-08-18 | 2021-09-30 | Biosplice Therapeutics, Inc. | Diketoni in hidroksiketoni, kot aktivatorji signalne poti katenina |
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- 2014-10-31 US US14/529,435 patent/US9265767B2/en not_active Expired - Fee Related
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- 2015-10-05 JP JP2015197316A patent/JP2016014061A/ja active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006072828A2 (en) * | 2005-01-07 | 2006-07-13 | Pfizer Products Inc. | Heteroaromatic quinoline compounds and their use as pde10 inhibitors |
| WO2007077490A2 (en) * | 2006-01-05 | 2007-07-12 | Pfizer Products Inc. | Bicyclic heteroaryl compounds as pde10 inhibitors |
| WO2007129183A2 (en) * | 2006-05-02 | 2007-11-15 | Pfizer Products Inc. | Bicyclic heteroaryl compounds as pde10 inhibitors |
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