Design and synthesis of novel pyrimidine analogs as highly selective, non-covalent BTK inhibitors

被引：14

作者：

Kawahata, Wataru ^{[1
]}

Asami, Tokiko ^{[1
]}

Irie, Takayuki ^{[1
]}

Sawa, Masaaki ^{[1
]}

机构：

[1] Carna Biosci Inc, Res & Dev, BMA, Chuo Ku, 3rd Floor,1-5-5 Minatojima Minamimachi, Kobe, Hyogo 6500047, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2018年 / 28卷 / 02期

关键词：

Bruton's tyrosine kinase; Kinase inhibitor; Kinase selectivity; Pyrimidine; Passive cutaneous anaphylaxis; BRUTONS TYROSINE KINASE; TEC FAMILY KINASES; B-CELL; ARTHRITIS; POTENT;

D O I：

10.1016/j.bmcl.2017.11.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

BTK is a promising target for the treatment of multiple diseases such as B cell malignances, asthma, and rheumatoid arthritis. Here, we report the discovery of a series of novel pyrimidine analogs as potent, highly selective, non-covalent inhibitors of BTK. Compound 25d demonstrated higher affinity to an unactivated conformation of BTK that resulted in an excellent kinase selectivity. Compound 25d showed a good oral bioavailability in mice, and significantly inhibits the PCA reaction in mice. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：145 / 151

页数：7

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