Synthesis, preliminary biological evaluation and molecular modeling of some new heterocyclic inhibitors of TACE

► New TACE inhibitors based on BMS-566394 scaffold were synthesized. ► Effect of replacement of the central phenyl ring with heteroaryl rings on the TACE inhibitory activity was studied. ► In vitro potency increased when central ring was pyridine whereas decreased in case of five member heterocycles. ► This observation was supported by in silico molecular modeling studies.