Design, synthesis and biological assessment of novel CDK4 inhibitor with potent anticancer activity.

Efforts toward finding potent CDK4 inhibitor for cancer therapy, a series of fluorine substituted pyrrolo[2,3-d]pyrimidine derivatives were designed, synthesized, and evaluated. Among them, the optimal lead compound 18i was discovered with potent activity against CDK4 at the nanomolar level (IC = 2.5 nM) and exquisite selectivity which demonstrated only modest activity against 3 out of the 394 protein kinases.