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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Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2610MU2008 | 2008-12-15 | ||
| US14113308P | 2008-12-29 | 2008-12-29 | |
| IN145MU2009 | 2009-01-22 | ||
| US15024809P | 2009-02-05 | 2009-02-05 | |
| IN1397MU2009 | 2009-06-10 | ||
| US22161509P | 2009-06-30 | 2009-06-30 | |
| IN1730MU2009 | 2009-07-29 | ||
| US23745609P | 2009-08-27 | 2009-08-27 |
Publications (1)
| Publication Number | Publication Date |
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| TW201022283A true TW201022283A (en) | 2010-06-16 |
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| TW098142756A TW201022283A (en) | 2008-12-15 | 2009-12-14 | Fused imidazole carboxamides as TRPV3 modulators |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8318928B2 (https=) |
| EP (1) | EP2367825A1 (https=) |
| JP (1) | JP2012512151A (https=) |
| AR (1) | AR076830A1 (https=) |
| AU (1) | AU2009329192A1 (https=) |
| CA (1) | CA2746077A1 (https=) |
| EA (1) | EA201190004A1 (https=) |
| GE (1) | GEP20146099B (https=) |
| MX (1) | MX2011006132A (https=) |
| NZ (1) | NZ595777A (https=) |
| TW (1) | TW201022283A (https=) |
| WO (1) | WO2010070452A1 (https=) |
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| AU2009332651A1 (en) * | 2008-12-26 | 2011-12-01 | Glenmark Pharmaceuticals, S.A. | Fused imidazole derivatives as TRPV3 antagonist |
| PH12013500275A1 (en) | 2010-08-10 | 2017-08-23 | Abbvie Inc | Novel trpv3 modulators |
| 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 |
| US9012651B2 (en) | 2011-03-24 | 2015-04-21 | Abbvie Inc. | TRPV3 modulators |
| JP2014510768A (ja) | 2011-04-11 | 2014-05-01 | グラクソ グループ リミテッド | Ｔｒｐｖ１アンタゴニストとしてのｎ−シクロブチルイミダゾピリジンメチルアミン |
| WO2013062966A2 (en) | 2011-10-24 | 2013-05-02 | Abbvie Inc. | Novel trpv3 modulators |
| US9605002B2 (en) * | 2012-07-18 | 2017-03-28 | University Of Notre Dame Du Lac | 5,5-heteroaromatic anti-infective compounds |
| HRP20220636T1 (hr) | 2016-12-09 | 2022-07-22 | Denali Therapeutics Inc. | Spojevi korisni kao inhibitori ripk1 |
| US12030875B2 (en) | 2018-09-07 | 2024-07-09 | PIC Therapeutics, Inc. | EIF4E inhibitors and uses thereof |
| EP4096661B1 (en) | 2020-01-29 | 2025-04-02 | Kamari Pharma Ltd. | Compounds and compositions for use in treating skin disorders |
| AU2021230289A1 (en) | 2020-03-03 | 2022-09-29 | PIC Therapeutics, Inc. | eIF4E inhibitors and uses thereof |
| JP2024534127A (ja) | 2021-08-25 | 2024-09-18 | 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 |
| US12157732B2 (en) | 2021-08-25 | 2024-12-03 | PIC Therapeutics, Inc. | eIF4E inhibitors and uses thereof |
Family Cites Families (19)
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| NO811630L (no) | 1980-05-29 | 1981-11-30 | Bayer Ag | Imidazoazolalkensyreamider, nye mellomprodukter for deres fremstilling, deres fremstilling og deres anvendelse som legemiddel |
| 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 |
| US20080145819A1 (en) | 2004-08-18 | 2008-06-19 | Robert Boettcher | Screw-in Enossal Dental Implant |
| JP2008523145A (ja) | 2004-12-13 | 2008-07-03 | イーライ リリー アンド カンパニー | リポキシゲナーゼ阻害剤としてのスピロ誘導体 |
| WO2007042906A1 (en) | 2005-10-07 | 2007-04-19 | Glenmark Pharmaceuticals S.A. | Substituted benzofused derivatives and their use as vanilloid receptor ligands |
| US7893260B2 (en) | 2005-11-04 | 2011-02-22 | Hydra Biosciences, Inc. | Substituted quinazolin-4-one compounds for antagonizing TRPV3 function |
| WO2008001101A2 (en) | 2006-06-29 | 2008-01-03 | Astex Therapeutics Limited | Pharmaceutical combinations |
| EP2049119A2 (en) | 2006-06-29 | 2009-04-22 | Astex Therapeutics Limited | Pharmaceutical combinations of 1-cyclopropyl-3-[3-(5-morphoolin-4-ylmethyl-1h-benzoimidazol-2-yl)-1h-1-pyrazol-4-yl]-urea |
| 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 |
| EP2139894B1 (en) | 2007-03-19 | 2011-10-26 | AstraZeneca AB | 9-substituted-8-oxo-adenine compounds as toll-like receptor (tlr7) modulators |
| WO2008140750A1 (en) | 2007-05-10 | 2008-11-20 | Hydra Biosciences Inc. | Compounds for modulating trpv3 function |
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- 2009-12-14 TW TW098142756A patent/TW201022283A/zh unknown
- 2009-12-15 MX MX2011006132A patent/MX2011006132A/es unknown
- 2009-12-15 CA CA2746077A patent/CA2746077A1/en not_active Abandoned
- 2009-12-15 AR ARP090104861A patent/AR076830A1/es not_active Application Discontinuation
- 2009-12-15 NZ NZ595777A patent/NZ595777A/xx not_active IP Right Cessation
- 2009-12-15 GE GEAP200912526A patent/GEP20146099B/en unknown
- 2009-12-15 EP EP09806128A patent/EP2367825A1/en not_active Withdrawn
- 2009-12-15 EA EA201190004A patent/EA201190004A1/ru unknown
- 2009-12-15 AU AU2009329192A patent/AU2009329192A1/en not_active Abandoned
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| EP2367825A1 (en) | 2011-09-28 |
| WO2010070452A1 (en) | 2010-06-24 |
| MX2011006132A (es) | 2011-09-01 |
| US8318928B2 (en) | 2012-11-27 |
| EA201190004A1 (ru) | 2012-11-30 |
| US20100152192A1 (en) | 2010-06-17 |
| JP2012512151A (ja) | 2012-05-31 |
| GEP20146099B (en) | 2014-05-27 |
| CA2746077A1 (en) | 2010-06-24 |
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