The design, synthesis, and structure-activity relationships of a series of macrocyclic MMP inhibitors

Article abstract of DOI:10.1016/S0960-894X(98)00396-5

A series of succinate-derived hydroxamic acids incorporating a macrocyclic ring were designed, synthesized, and evaluated as inhibitors of matrix metalloproteinases. The inhibitors were designed based on the published X-ray crystal structure of batimastat (1) complexed with human neutrophil collagenase (MMP-8). The synthesized compounds were shown to inhibit selected MMPs in vitro with low nanomolar potency.