Expanding the structural diversity of Bcr-Abl inhibitors: Dibenzoylpiperazin incorporated with 1H-indazol-3-amine

A series of N,N'-dibenzoylpiperazine derivatives incorporated with 1H-indazol-3-amine have been designed, synthesized and evaluated as novel Bcr-Abl inhibitors. Several title compounds exhibited potent inhibitory activity against Bcr-Abl wild type as well as T315I mutant. Two compounds, ha and 12c, strongly suppressed the activity of native and mutant Bcr-Abl. In particular, ha exhibited comparable potency with that of Imatinib. It potently inhibited both Bcr-Abl(WT) and Bcr-AbI(T3151) with IC50 values of 0.014 mu M and 0.45 mu M, respectively. Furthermore, compound ha also inhibited the proliferation of K562 leukemia cancer cells. Therefore, it could serve as promising lead compound for further optimization of Bcr-Abl(WT) and Bcr-Abl(T3151) inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.