Design, Synthesis, and Biological Evaluation of Matrix Metalloproteinase Inhibitors Derived from a Modified Proline Scaffold

The synthesis and structure−activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp2 center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically