Discovery of novel Bcr-Abl inhibitors with diacylated piperazine as the flexible linker?

Organic & Biomolecular Chemistry Pub Date: 2015-05-21 DOI: 10.1039/C5OB00430F

Abstract

Forty-two compounds (series 8, 9 and 10) incorporated with diacylated piperazine have been synthesized and evaluated as novel Bcr-Abl inhibitors based on ‘six-atom linker’. Five of them, 8d, 8h, 8l, 10m and 10p, displayed potent Bcr-Abl inhibitory activity comparable with Imatinib. Moreover, compounds 8e, 10q, 10s, and 10u were potent Bcr-Abl inhibitors with IC50 values at the sub-micromolecular level. Most compounds exhibited moderate to high antiproliferative activity against K562 cells. In particular, compound 9e was the most promising Bcr-Abl inhibitor. Docking studies revealed that the binding modes of these compounds were similar with Imatinib. These compounds could be considered as promising lead compounds for further optimization.

Graphical abstract: Discovery of novel Bcr-Abl inhibitors with diacylated piperazine as the flexible linker
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