Synthesis of α-trifluoromethyl-α-amino-β-sulfone hydroxamates: novel nanomolar inhibitors of matrix metalloproteinases

…, M Sani, G Candiani, R Parente, F Pecker, S Bellosta…

Index: Sinisi, Roberta; Sani, Monica; Candiani, Gabriele; Parente, Rachele; Pecker, Francoise; Bellosta, Stefano; Zanda, Matteo Tetrahedron Letters, 2005 , vol. 46, # 38 p. 6515 - 6518

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Citation Number: 14

Abstract

The racemic α-trifluoromethyl-α-amino-β-sulfone hydroxamates were synthesized by means of a nucleophilic addition of sulfur-stabilized carbanions to a N-Cbz imine of trifluoropyruvate (). The free amino derivative was the most potent inhibitor of both MMP-3 (stromelysin-1) and MMP-9 (gelatinase-B), showing an IC50= 14nM and 1nM, respectively, and excellent selectivity versus MMP-1 (> 5000-fold difference in inhibitory capacity). The N-Me ...