AU2007235237B2 - Thiazoles, imidazoles, and pyrazoles useful as inhibitors of protein kinases - Google Patents
Thiazoles, imidazoles, and pyrazoles useful as inhibitors of protein kinases Download PDFInfo
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- AU2007235237B2 AU2007235237B2 AU2007235237A AU2007235237A AU2007235237B2 AU 2007235237 B2 AU2007235237 B2 AU 2007235237B2 AU 2007235237 A AU2007235237 A AU 2007235237A AU 2007235237 A AU2007235237 A AU 2007235237A AU 2007235237 B2 AU2007235237 B2 AU 2007235237B2
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Classifications
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US79108306P | 2006-04-11 | 2006-04-11 | |
| US60/791,083 | 2006-04-11 | ||
| PCT/US2007/008819 WO2007117692A2 (en) | 2006-04-11 | 2007-04-11 | Thiazoles, imidazoles, and pyrazoles useful as inhibitors of protein kinases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2007235237A1 AU2007235237A1 (en) | 2007-10-18 |
| AU2007235237B2 true AU2007235237B2 (en) | 2011-08-18 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2007235237A Ceased AU2007235237B2 (en) | 2006-04-11 | 2007-04-11 | Thiazoles, imidazoles, and pyrazoles useful as inhibitors of protein kinases |
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| Country | Link |
|---|---|
| US (3) | US7589214B2 (https=) |
| EP (1) | EP2007732B1 (https=) |
| JP (1) | JP2009536617A (https=) |
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| AT (1) | ATE534632T1 (https=) |
| AU (1) | AU2007235237B2 (https=) |
| CA (1) | CA2648923A1 (https=) |
| ES (1) | ES2376765T3 (https=) |
| WO (1) | WO2007117692A2 (https=) |
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| WO2007117692A2 (en) * | 2006-04-11 | 2007-10-18 | Vertex Pharmaceuticals Incorporated | Thiazoles, imidazoles, and pyrazoles useful as inhibitors of protein kinases |
| RU2528231C2 (ru) * | 2009-04-24 | 2014-09-10 | Тиботек Фармасьютикалз | Диариловые эфиры |
| US8735417B2 (en) | 2009-12-17 | 2014-05-27 | Merck Sharp & Dohme Corp. | Aminopyrimidines as Syk inhibitors |
| WO2011075517A1 (en) | 2009-12-17 | 2011-06-23 | Merck Sharp & Dohme Corp. | Aminopyrimidines as syk inhibitors |
| MX2013013090A (es) | 2011-05-10 | 2013-12-16 | Merck Sharp & Dohme | Aminopirimidinas como inhibidores de tirosina cinaza del bazo. |
| US9145391B2 (en) | 2011-05-10 | 2015-09-29 | Merck Sharp & Dohme Corp. | Bipyridylaminopyridines as Syk inhibitors |
| EP2707357B1 (en) | 2011-05-10 | 2017-01-18 | Merck Sharp & Dohme Corp. | Pyridyl aminopyridines as syk inhibitors |
| JP6170944B2 (ja) | 2011-12-28 | 2017-07-26 | ヤンセン・サイエンシズ・アイルランド・ユーシー | Ｈｃｖ阻害剤としてのヘテロ−二環式誘導体 |
| SG11201500499TA (en) | 2012-08-10 | 2015-03-30 | Boehringer Ingelheim Int | Heteroaromatic compounds as bruton's tyrosine kinase (btk) inhibitors |
| JP6178861B2 (ja) | 2012-11-02 | 2017-08-09 | ファイザー・インク | ブルトン型チロシンキナーゼ阻害剤 |
| CN103848810A (zh) | 2012-11-30 | 2014-06-11 | 北京赛林泰医药技术有限公司 | 鲁顿酪氨酸激酶抑制剂 |
| JP6403751B2 (ja) * | 2013-03-14 | 2018-10-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ５−チアゾールカルボキサミン誘導体及びｂｔｋ阻害剤としてのその使用 |
| WO2014152114A1 (en) | 2013-03-15 | 2014-09-25 | Boehringer Ingelheim International Gmbh | Heteroaromatic compounds as btk inhibitors |
| JP6615752B2 (ja) * | 2013-09-30 | 2019-12-04 | グアンジョウ・イノケア・ファーマ・テク・カンパニー・リミテッド | Ｂｔｋの置換ニコチンイミド阻害剤およびそれらの調製、ならびにがん、炎症および自己免疫疾患の治療における使用 |
| BR112016013540B1 (pt) | 2013-12-13 | 2021-03-02 | F. Hoffmann-La Roche Ag | inibidores de tirosina quinase de bruton |
| WO2015116485A1 (en) * | 2014-01-29 | 2015-08-06 | Boehringer Ingelheim International Gmbh | Pyrazole compounds as btk inhibitors |
| CN105085474B (zh) * | 2014-05-07 | 2018-05-18 | 北京赛林泰医药技术有限公司 | 鲁顿酪氨酸激酶抑制剂 |
| TW201607930A (zh) * | 2014-07-18 | 2016-03-01 | 百濟神州有限公司 | 作為ｔ７９０ｍ／ｗｔ－ｅｇｆｒ的選擇性和不可逆的激酶抑制劑的５－氨基－４－氨甲醯基－吡唑化合物及其用途 |
| US9975882B2 (en) | 2015-12-16 | 2018-05-22 | Boehringer Ingelheim International Gmbh | Heteroaromatic compounds as BTK inhibitors |
| US10570118B2 (en) | 2016-01-13 | 2020-02-25 | Boehringer Ingelheim International Gmbh | Isoquinolones as BTK inhibitors |
| WO2020173407A1 (en) * | 2019-02-25 | 2020-09-03 | Beijing Innocare Pharma Tech Co., Ltd. | Process for preparing 6- (1-acryloylpiperidin-4-yl) -2- (4-phenoxyphenyl) nicotinamide |
| WO2022012550A1 (en) * | 2020-07-13 | 2022-01-20 | Henan Normal University | Substituted 1h-imidazo [1, 2-b] pyrazole-3-carboxamide as bruton's tyrosine kinase inhibitors |
Citations (1)
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|---|---|---|---|---|
| WO2005012256A1 (en) * | 2003-07-22 | 2005-02-10 | Astex Therapeutics Limited | 3, 4-disubstituted 1h-pyrazole compounds and their use as cyclin dependent kinases (cdk) and glycogen synthase kinase-3 (gsk-3) modulators |
Family Cites Families (7)
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| GB9608435D0 (en) * | 1996-04-24 | 1996-06-26 | Celltech Therapeutics Ltd | Chemical compounds |
| US6288061B1 (en) * | 1997-12-26 | 2001-09-11 | Welfide Corporation | Imidazole derivatives |
| EP1317450B1 (en) * | 2000-09-15 | 2006-11-22 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| WO2002064136A2 (en) * | 2001-01-26 | 2002-08-22 | Chugai Seiyaku Kabushiki Kaisha | Malonyl-coa decarboxylase inhibitors useful as metabolic modulators |
| WO2005123671A1 (ja) * | 2004-06-22 | 2005-12-29 | Taisho Pharmaceutical Co., Ltd. | ピロール誘導体 |
| FR2881426B1 (fr) | 2005-02-03 | 2007-03-30 | Aventis Pharma Sa | Pyrolles et imidazoles substitues, compositions les contenant, procede de frabrication et utilisation |
| WO2007117692A2 (en) * | 2006-04-11 | 2007-10-18 | Vertex Pharmaceuticals Incorporated | Thiazoles, imidazoles, and pyrazoles useful as inhibitors of protein kinases |
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2007
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- 2007-04-11 EP EP07755181A patent/EP2007732B1/en not_active Not-in-force
- 2007-04-11 CN CN2007800208154A patent/CN101460466B/zh not_active Expired - Fee Related
- 2007-04-11 ES ES07755181T patent/ES2376765T3/es active Active
- 2007-04-11 US US11/786,464 patent/US7589214B2/en not_active Expired - Fee Related
- 2007-04-11 AU AU2007235237A patent/AU2007235237B2/en not_active Ceased
- 2007-04-11 CA CA002648923A patent/CA2648923A1/en not_active Abandoned
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005012256A1 (en) * | 2003-07-22 | 2005-02-10 | Astex Therapeutics Limited | 3, 4-disubstituted 1h-pyrazole compounds and their use as cyclin dependent kinases (cdk) and glycogen synthase kinase-3 (gsk-3) modulators |
Also Published As
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|---|---|
| EP2007732B1 (en) | 2011-11-23 |
| WO2007117692A3 (en) | 2008-01-10 |
| ES2376765T3 (es) | 2012-03-16 |
| EP2007732A2 (en) | 2008-12-31 |
| WO2007117692A2 (en) | 2007-10-18 |
| CN101460466A (zh) | 2009-06-17 |
| US20130090479A1 (en) | 2013-04-11 |
| CA2648923A1 (en) | 2007-10-18 |
| JP2009536617A (ja) | 2009-10-15 |
| ATE534632T1 (de) | 2011-12-15 |
| US20070298065A1 (en) | 2007-12-27 |
| AU2007235237A1 (en) | 2007-10-18 |
| US7589214B2 (en) | 2009-09-15 |
| US8236832B2 (en) | 2012-08-07 |
| US20090306155A1 (en) | 2009-12-10 |
| CN101460466B (zh) | 2012-06-13 |
| US8865751B2 (en) | 2014-10-21 |
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