TW201022283A - Fused imidazole carboxamides as TRPV3 modulators - Google Patents
Fused imidazole carboxamides as TRPV3 modulators Download PDFInfo
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- TW201022283A TW201022283A TW098142756A TW98142756A TW201022283A TW 201022283 A TW201022283 A TW 201022283A TW 098142756 A TW098142756 A TW 098142756A TW 98142756 A TW98142756 A TW 98142756A TW 201022283 A TW201022283 A TW 201022283A
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- 102000003568 TRPV3 Human genes 0.000 title abstract 3
- 101150043371 Trpv3 gene Proteins 0.000 title abstract 3
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Classifications
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Landscapes
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| JP2013538800A (ja) * | 2010-08-10 | 2013-10-17 | アッヴィ・インコーポレイテッド | 新規ｔｒｐｖ３モジュレーター |
| WO2012072512A1 (en) * | 2010-11-29 | 2012-06-07 | Glaxo Group Limited | N-cyclobutyl-imidazopyridine or -pyrazolopyridine carboxamides as trpv1 antagonists |
| KR101834362B1 (ko) | 2011-03-18 | 2018-03-05 | 바이엘 인텔렉쳐 프로퍼티 게엠베하 | N-(3-카바모일페닐)-1h-피라졸-5-카복사미드 유도체 및 동물 해충을 구제하기 위한 그의 용도 |
| WO2012129491A1 (en) | 2011-03-24 | 2012-09-27 | Abbott Laboratories | Trpv3 modulators |
| US8754101B2 (en) | 2011-04-11 | 2014-06-17 | Glaxo Group Limited | N-cyclobutyl-imidazopyridine-methylamine as TRPV1 antagonists |
| CA2853097A1 (en) | 2011-10-24 | 2013-05-02 | Abbvie Inc. | Novel trpv3 modulators |
| CN104718213B (zh) * | 2012-07-18 | 2018-02-27 | 圣母大学 | 5,5‑杂芳族抗感染化合物 |
| EP3552017B1 (en) * | 2016-12-09 | 2022-02-23 | Denali Therapeutics Inc. | Compounds useful as ripk1 inhibitors |
| EP3846793B1 (en) | 2018-09-07 | 2024-01-24 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
| CN118702672A (zh) | 2020-01-29 | 2024-09-27 | 卡玛瑞制药有限公司 | 用于治疗皮肤病症的化合物和组合物 |
| TW202146393A (zh) | 2020-03-03 | 2021-12-16 | 美商皮克醫療公司 | Eif4e抑制劑及其用途 |
| CN118103368A (zh) | 2021-08-25 | 2024-05-28 | 皮克医疗公司 | Eif4e抑制剂及其用途 |
| JP2024532276A (ja) | 2021-08-25 | 2024-09-05 | ピク セラピューティクス， インコーポレイテッド | ｅＩＦ４Ｅ阻害剤及びその使用 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4444770A (en) * | 1980-05-29 | 1984-04-24 | Bayer Aktiengesellschaft | New imidazoazole-alkenoic acid amide compounds, intermediate products for their production, their production, and their medicinal use |
| US5204352A (en) * | 1987-09-29 | 1993-04-20 | The United States Of America As Represented By The Secretary Of The Army | Compounds exhibiting anti-parasitic activity and a method for their use |
| GB8820231D0 (en) * | 1988-08-25 | 1988-09-28 | Fujisawa Pharmaceutical Co | New benzazole compounds processes for preparation thereof & pharmaceutical composition comprising same |
| JPH02105085A (ja) | 1988-10-14 | 1990-04-17 | Komatsu Ltd | 磁気センサ |
| JPH07242666A (ja) | 1994-03-08 | 1995-09-19 | Fujisawa Pharmaceut Co Ltd | 複素環化合物 |
| WO1999051587A1 (en) * | 1998-04-01 | 1999-10-14 | Ono Pharmaceutical Co., Ltd. | Fused thiophene derivatives and drugs containing the same as the active ingredient |
| US20040009537A1 (en) * | 2002-01-11 | 2004-01-15 | Jack Roos | Methods of modulating and of identifying agents that modulate intracellular calcium |
| TWI372050B (en) * | 2003-07-03 | 2012-09-11 | Astex Therapeutics Ltd | (morpholin-4-ylmethyl-1h-benzimidazol-2-yl)-1h-pyrazoles |
| US20060074124A1 (en) * | 2003-09-12 | 2006-04-06 | Andrew Napper | Methods of treating a disorder |
| ATE369806T1 (de) | 2004-08-18 | 2007-09-15 | Robert Boettcher | Einschraubbares enossales dentalimplantat |
| MX2007007103A (es) | 2004-12-13 | 2008-03-10 | Lilly Co Eli | Derivados espiro como inhibidores de lipoxigenasa. |
| AP2008004432A0 (en) | 2005-10-07 | 2008-04-30 | Glenmark Pharmaceuticals Sa | Substituted benzofused derivatives and their use as vanilloid receptor ligands |
| AU2006311883A1 (en) * | 2005-11-04 | 2007-05-18 | Hydra Biosciences, Inc. | Compounds for modulating TRPV3 function |
| JP2009542608A (ja) | 2006-06-29 | 2009-12-03 | アステックス・セラピューティクス・リミテッド | 医薬組合せ剤 |
| JP5523829B2 (ja) | 2006-06-29 | 2014-06-18 | アステックス、セラピューティックス、リミテッド | 複合薬剤 |
| EP2049548A1 (en) | 2006-07-27 | 2009-04-22 | UCB Pharma, S.A. | Fused oxazoles & thiazoles as histamine h3- receptor ligands |
| WO2008033564A1 (en) | 2006-09-15 | 2008-03-20 | Hydra Biosciences Inc. | Compounds for modulating trpv3 function |
| JP5329444B2 (ja) | 2007-03-19 | 2013-10-30 | アストラゼネカ・アクチエボラーグ | Ｔｏｌｌ様受容体（ｔｌｒ７）モジュレーターとしての９−置換−８−オキソ−アデニン化合物 |
| WO2008140750A1 (en) | 2007-05-10 | 2008-11-20 | Hydra Biosciences Inc. | Compounds for modulating trpv3 function |
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2009
- 2009-12-11 US US12/636,213 patent/US8318928B2/en not_active Expired - Fee Related
- 2009-12-14 TW TW098142756A patent/TW201022283A/zh unknown
- 2009-12-15 NZ NZ595777A patent/NZ595777A/xx not_active IP Right Cessation
- 2009-12-15 EA EA201190004A patent/EA201190004A1/ru unknown
- 2009-12-15 AU AU2009329192A patent/AU2009329192A1/en not_active Abandoned
- 2009-12-15 JP JP2011540235A patent/JP2012512151A/ja active Pending
- 2009-12-15 EP EP09806128A patent/EP2367825A1/en not_active Withdrawn
- 2009-12-15 AR ARP090104861A patent/AR076830A1/es not_active Application Discontinuation
- 2009-12-15 MX MX2011006132A patent/MX2011006132A/es unknown
- 2009-12-15 GE GEAP200912526A patent/GEP20146099B/en unknown
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- 2009-12-15 CA CA2746077A patent/CA2746077A1/en not_active Abandoned
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| EP2367825A1 (en) | 2011-09-28 |
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| WO2010070452A1 (en) | 2010-06-24 |
| AU2009329192A2 (en) | 2012-03-29 |
| US20100152192A1 (en) | 2010-06-17 |
| AR076830A1 (es) | 2011-07-13 |
| MX2011006132A (es) | 2011-09-01 |
| CA2746077A1 (en) | 2010-06-24 |
| NZ595777A (en) | 2013-07-26 |
| US8318928B2 (en) | 2012-11-27 |
| EA201190004A1 (ru) | 2012-11-30 |
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