Discovery of Novel Bruton's Tyrosine Kinase (BTK) Inhibitors Bearing a N,9-Diphenyl-9H-purin-2-amine Scaffold.

ABSTRACT: Based on the pyrimidine skeleton of EGFRT790M inhibitors, a series of N,9-diphenyl-9H-purin-2-amine derivatives were identified as effective BTK inhibitors. Among these compounds, inhibitors 10d, 10i, and 10j, possessing IC50 values of 0.5, 0.5, and 0.4 nM, displayed anti-BTK kinase activity that was as potent as the reference compounds. In particular, compound 10j suppressed the proliferation of two typical B-cell leukemia cell lines expressing high levels of BTK with concentrations of 7.75 and 12.6 ?M. The activity of the subject compound as determined by the CCK-8 method and apoptosis analysis validated that inhibitor 10j is slightly more potent than AVL-292 and ibrutinib. The results of these experimental explorations suggested that 10j could serve as a valuable molecule for control of leukemia pending further developments.

SUBMITTER: Ge Y 

PROVIDER: S-EPMC5150693 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature