Synthesis and biological evaluation of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent Bruton鈥檚 tyrosine kinase (BTK) inhibitors

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• 作者：Minhang Xin^a ; ^&dagger ; ; ^{xmhcpu@163.com" class="auth_mail" title="E-mail the corresponding author} ; Xinge Zhao^b ; ^&dagger ; ; Wei Huang^c ; Qiu Jin^b ; Gang Wu^b ; Yazhou Wang^b ; Feng Tang^b ; Hua Xiang^d ; ^{1020030692@cpu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BTK inhibitors ; Thieno[3 ; 2-c]pyrid-4-amine ; Inhibitory activity ; Kinase selectivity
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2015
• 出版时间：1 October 2015
• 年：2015
• 卷：23
• 期：19
• 页码：6250-6257
• 全文大小：2277 K

文摘

A series of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent BTK inhibitors were designed, synthesized and evaluated. These thieno[3,2-c]pyridin-4-amine derivatives displayed variant inhibitory activities against BTK in vitro. Among these, 7-pyrazol-4-yl substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amine subseries showed high BTK inhibition and several compounds displayed superior BTK inhibitory activity. Comprehensive SAR was disclosed and compound class="boldFont">13b showed excellent potency (IC₅₀ = 11.8 nM), outstanding hydrophilicity (A log P = 3.53), and relatively good kinase selectivity, being a promising lead for further evaluation.