Synthesis and biological evaluation of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3, 2-c]pyridin-4-amines as potent Bruton's tyrosine kinase (BTK) inhibitors. Issue 19 (1st October 2015)

• Record Type: Journal Article
• Authors: Xin, Minhang; Zhao, Xinge; Huang, Wei; Jin, Qiu; Wu, Gang; Wang, Yazhou; Tang, Feng; Xiang, Hua
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 19(2015)
• Page Start: 6250
• Page End: 6257
• Publication Date: 2015-10-01
• Subjects: BTK inhibitors -- Thieno[3, 2-c]pyrid-4-amine -- Inhibitory activity -- Kinase selectivity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.08.039
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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 compound13b 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.