Synthesis and biological evaluation of phenyl-amino-pyrimidine and indole/oxindole conjugates as potential BCR-ABL inhibitors

Abstract

Indole/isatin conjugated phenyl-amino-pyrimidine derivatives have been synthesized, characterized and evaluated in vitro for their potential as BCR-ABL inhibitors. Among the series, all derivatives (7a–7o) were found to be more cytotoxic than standard Imatinib against K-562 cell line. Compound 7l was the most active in the series with almost two folds more potency than imitanib (IC50 0.65 μM). In vitro enzymatic studies with recombinant ABL kinase enzyme exhibited promising inhibition in the range of 30–71 µM for most of these novel conjugates. In addition, modelling and other computational studies have been carried out to draw insight into the BCR-ABL protein interactions with the target molecules and drug like properties of the conjugates, respectively.