5426
J. Med. Chem. 1999, 42, 5426-5436
Design, Synthesis, and Biological Evaluation of Matrix Metalloproteinase Inhibitors Derived from a Modified Proline Scaffold Menyan Cheng, Biswanath De, Neil G. Almstead, Stanislaw Pikul, Martin E. Dowty, Charles R. Dietsch, C. Michelle Dunaway, Fei Gu, Lily C. Hsieh, Michael J. Janusz, Yetunde O. Taiwo, and Michael G. Natchus* Procter and Gamble Pharmaceuticals, 8700 Mason-Montgomery Road, Mason, Ohio 45040
Tomas Hudlicky and Martin Mandel† Department of Chemistry, University of Florida, Gainesville, Florida 32611 Received September 16, 1999
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
