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

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• 作者：Zhenhua Huang ; ^{kbp@kbpbiosciences.com" class="auth_mail" title="E-mail the corresponding author} ; Qian Zhang ; Lianzhong Yan ; Guizhen Zhong ; Linqi Zhang ; Xiaojuan Tan ; Yanli Wang
• 关键词：Bruton&rsquo ; s tyrosine kinase (BTK) ; Rheumatoid arthritis (RA) ; Collagen-induced arthritis (CIA) ; 1 ; 3-Diamino-pyrimidine
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：26
• 期：8
• 页码：1954-1957
• 全文大小：1380 K

文摘

By applying conformational restrictions, we were able to discover highly potent 1,3-diaminopyrimidine based covalent inhibitors of BTK, such as dFont">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.