Design, synthesis and biological evaluation of novel 3-substituted pyrazolopyrimidine derivatives as potent Bruton's tyrosine kinase (BTK) inhibitors

Publication date: Available online 12 March 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Nan Zheng, Jing Pan, Qun Hao, Yingxia Li, Weicheng Zhou
A series of 3-substituted pyrazolopyrimidine derivatives as BTK inhibitors were designed by structure-based drug design and they were synthesized, evaluated by enzyme-based assay and anti-proliferation against Ramos and Raji cells. Most of them displayed good inhibitory activities against both BTK and B-cell lymphoblastic leukemia lines in vitro. Among them, compound 8a exhibited excellent potency (IC50=7.95 nM against BTK enzyme, 8.91 μM against Ramos cells and 1.80 μM against Raji cells), with a better hydrophilicity (ClogP = 3.33). These explorations provided new clues to discover 3-substituted pyrazolopyrimidine derivatives as novel anti-tumor agents.

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