Novel highly potent, structurally simple gamma-trifluoromethyl gamma-sulfone hydroxamate inhibitor of stromelysin-1 (MMP-3)

The gamma-trifluoromethyl gamma-sulfone hydroxamate 1 was synthesized both in racemic and enantiomerically pure forms by means of a thia-Michael reaction of p-methoxythiophenol on achiral and chiral 3,3,3-trifluorocrotonoyl Michael acceptors. The (R)-1 enantiomer was the most potent inhibitor of MMP-3 (stromelysin-1), showing an IC50 = 3.2 nM, as well as the most selective with respect to MMP-9 (65-fold). (c) 2005 Elsevier Ltd. All rights reserved.