Approaching the active conformation of 1,3-diaminopyrimidine based covalent inhibitors of Bruton's tyrosine kinase for treatment of Rheumatoid arthritis

被引：13

作者：

Huang, Zhenhua ^{[1
]}

Zhang, Qian ^{[1
]}

Yan, Lianzhong ^{[1
]}

Zhong, Guizhen ^{[1
]}

Zhang, Linqi ^{[1
]}

Tan, Xiaojuan ^{[1
]}

Wang, Yanli ^{[1
]}

机构：

[1] KBP Biosci, C201,750 Shunhua Rd, Jinan 250101, Shandong, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 08期

关键词：

Bruton's tyrosine kinase (BTK); Rheumatoid arthritis (RA); Collagen-induced arthritis (CIA); 1,3-Diamino-pyrimidine; BINDING; BTK; DISCOVERY;

D O I：

10.1016/j.bmcl.2016.03.011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

By applying conformational restrictions, we were able to discover highly potent 1,3-diaminopyrimidine based covalent inhibitors of BTK, such as 8a (IC50 = 3.76 nM), and providing useful information of its active conformation. We are developing these novel small molecule covalent inhibitors of BTK toward oral agents for Rheumatoid arthritis. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1954 / 1957

页数：4

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