Discovery of β-benzamido hydroxamic acids as potent, selective, and orally bioavailable TACE inhibitors

β-Benzamido hydroxamic acids were discovered as potent TACE inhibitors. A computer model was constructed to help understanding the binding activities and guiding SAR study. SAR optimization led to the discovery of compound 30 which met all in vitro and in vivo criteria for the program and was selected for further evaluation.