Aryl[a]pyrrolo[3,4-c]carbazoles as selective cyclin D1-CDK4 inhibitors

Abstract The synthesis of new analogues of Arcyriaflavin A in which one indole ring is replaced by an aryl or heteroaryl ring is described. These new series of aryl[ a ]pyrrolo[3,4- c ]carbazoles were evaluated as inhibitors of Cyclin D1-CDK4. A potent and selective D1-CDK4 inhibitor, 7a (D1-CDK4 IC 50 =45 nM), has been identified. The potency, selectivity profile against other kinases, and structure–activity relationship (SAR) trends of this class of compounds are discussed.