Synthesis and Kinetic Study of Sulfonates-Thiiranes as Gelatinase Inhibitors; poster

TESTERO, S.A.; LEE, M.; STARAN, R.; ESPAHBODI, M.; LLARRULL, L.I.; TOTH, M.; CHANG M.; MOBASHERY, S.

Villa Carlos Paz

Congreso; XVIII Simposio Nacional de Química Orgánica; 2011

Sociedad Argentina de Investigaciones en Química Orgánica

Matrix metalloproteinases (MMPs), a family of 26 closely related zinc-dependent endopeptidases, possess important pathological and physiological functions. Their unregulated and uncontrolled activities have been associated with a number of disease processes, including neurological disorders, arthritis, cardiovascular diseases, and cancer, just to mention a few. Virtually all known MMP inhibitors were developed to chelate the active-site zinc ions of these enzymes, and as such they are broad-spectrum inhibitors. This lack of selectivity has been problematic in clinical trials of MMP inhibitors, as the molecules show serious side effects. We have previously described the synthesis, MMP inhibitory activity, mechanism and metabolic studies of the thiirane-containing structure 1, which possess a potent and selective inhibition of gelatinases (MMP-2 and MMP-9). We report herein the synthesis and evaluation of a series of sulfonyl-thiirane compounds of general structures 2 and 3, which exhibit potent and selective inhibition of gelatinases.