CN106188029A - Two and ring class anaplastic lymphoma kinase ALK Alk receptor tyrosine kinase inhibitor - Google Patents
Two and ring class anaplastic lymphoma kinase ALK Alk receptor tyrosine kinase inhibitor Download PDFInfo
- Publication number
- CN106188029A CN106188029A CN201510224442.9A CN201510224442A CN106188029A CN 106188029 A CN106188029 A CN 106188029A CN 201510224442 A CN201510224442 A CN 201510224442A CN 106188029 A CN106188029 A CN 106188029A
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- Prior art keywords
- alkyl
- amino
- hydroxyl
- yuan
- alkoxyl
- Prior art date
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- 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 title abstract description 22
- 101710168331 ALK tyrosine kinase receptor Proteins 0.000 title abstract description 17
- 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 title abstract description 5
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- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- -1 nitro, carboxyl Chemical group 0.000 claims description 253
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 46
- 229910052721 tungsten Inorganic materials 0.000 claims description 46
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 45
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 43
- 229910052799 carbon Inorganic materials 0.000 claims description 36
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
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CN114555585A (en) * | 2019-07-04 | 2022-05-27 | 上海齐鲁锐格医药研发有限公司 | HPK1 inhibitors and uses thereof |
EP4103182A4 (en) * | 2020-02-14 | 2024-02-21 | Salk Institute for Biological Studies | Inhibitors of ulk1/2 and methods of using same |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997019065A1 (en) * | 1995-11-20 | 1997-05-29 | Celltech Therapeutics Limited | Substituted 2-anilinopyrimidines useful as protein kinase inhibitors |
CN101039919A (en) * | 2004-10-13 | 2007-09-19 | 惠氏公司 | N-benzenesulfonyl substituted anilino-pyrimidine analogs |
EP1903045A1 (en) * | 2005-05-27 | 2008-03-26 | Mitsubishi Tanabe Pharma Corporation | Pyrazolopyrimidine derivative |
WO2008086158A1 (en) * | 2007-01-04 | 2008-07-17 | Smithkline Beecham Corporation | Benzodihydroquinazoline as pi3 kinase inhibitors |
US20090048282A1 (en) * | 2007-08-14 | 2009-02-19 | Wyeth | Pyrimidine sulfonamide analogs and their use as agonists of the wnt-beta-catenin cellular messaging system |
CN101568529A (en) * | 2006-12-22 | 2009-10-28 | 诺瓦提斯公司 | Heteroaryl-heteroaryl compounds as cdk inhibitors for the treatment of cancer, inflammation and viral infections |
CN102482277A (en) * | 2009-05-05 | 2012-05-30 | 达纳-法伯癌症研究所有限公司 | Egfr inhibitors and methods of treating disorders |
-
2015
- 2015-05-05 CN CN201510224442.9A patent/CN106188029B/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997019065A1 (en) * | 1995-11-20 | 1997-05-29 | Celltech Therapeutics Limited | Substituted 2-anilinopyrimidines useful as protein kinase inhibitors |
CN101039919A (en) * | 2004-10-13 | 2007-09-19 | 惠氏公司 | N-benzenesulfonyl substituted anilino-pyrimidine analogs |
EP1903045A1 (en) * | 2005-05-27 | 2008-03-26 | Mitsubishi Tanabe Pharma Corporation | Pyrazolopyrimidine derivative |
CN101568529A (en) * | 2006-12-22 | 2009-10-28 | 诺瓦提斯公司 | Heteroaryl-heteroaryl compounds as cdk inhibitors for the treatment of cancer, inflammation and viral infections |
WO2008086158A1 (en) * | 2007-01-04 | 2008-07-17 | Smithkline Beecham Corporation | Benzodihydroquinazoline as pi3 kinase inhibitors |
US20090048282A1 (en) * | 2007-08-14 | 2009-02-19 | Wyeth | Pyrimidine sulfonamide analogs and their use as agonists of the wnt-beta-catenin cellular messaging system |
CN102482277A (en) * | 2009-05-05 | 2012-05-30 | 达纳-法伯癌症研究所有限公司 | Egfr inhibitors and methods of treating disorders |
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