Synthesis and biological evaluation of imidazo[4,5-b]pyridine and 4-heteroaryl-pyrimidine derivatives as anti-cancer agents

A series of N-phenyl-imidazo[4,5-b]pyridin-2-amines, 4-indazolyl-N-phenylpyrimidin-2-amines and N-phenyl-4-pyrazolo[3,4-b]pyridin-pyrimidin-2-amines have been synthesized. Their anti-proliferative activities were tested in HCT-116 human colon carcinoma and MCF-7 breast carcinoma cell lines. Many exhibited potent anti-proliferative and CDK9 inhibitory activities. A lead compound 18b demonstrated the ability to reduce the level of Mcl-1 anti-apoptotic protein, to activate caspase 3/7 and induce cancer cell apoptosis. [Display omitted] ► We prepared imidazo[4,5-b]pyridine and 4-heteroaryl-pyrimidine derivatives. ► The structure and biological activity relationship was evaluated. ► Many exhibited potent anti-proliferative and CDK9 inhibitory activities. ► A lead 18b activated caspase 3/7 activity and induced apoptosis.