Validating the 1,2-Difluoro Motif As a Hybrid Bioisostere of CF₃ and Et Using Matrix Metalloproteinases As Structural Probes

Matrix metalloproteinases (MMPs) are involved in a spectrum of physiological processes, rendering them attractive targets for small-molecule drug discovery. Strategies to achieve selective inhibition continue to be intensively pursued, facilitated by advances in structural biology. Herein, we harness MMPs 2, 8, 9, and 13 to validate the vicinal difluoro motif as a hybrid bioisostere of CF3 and Et (BITE) in a series of modified barbiturate...