The racemic alpha-trifluoromethyl-alpha-amino-beta-sulfone hydroxamates 1 were synthesized by means of a nucleophilic addition of sulfur-stabilized carbanions to a N-Cbz imine of trifluoropyruvate (4). The free amino derivative 1a was the most potent inhibitor of both MMP-3 (stromelysin-1) and MMP-9 (gelatinase-B), showing an IC50 = 14 nM and 1 nM, respectively, and excellent selectivity versus MMP- 1 (>5000-fold difference in inhibitory capacity). The N-Me derivative 1b was the most selective for MMP-3 with respect to MMP-9 (62-fold difference). (c) 2005 Elsevier Ltd. All rights reserved.
Synthesis of alpha-trifluoromethyl-alpha-amino-beta-sulfone hydroxamates : novel nanomolar inhibitors of matrix metalloproteinases / R. Sinisi, M. Sani, G. Candiani, R. Parente, F. Pecker, S. Bellosta, M. Zanda. - In: TETRAHEDRON LETTERS. - ISSN 0040-4039. - 46:38(2005), pp. 6515-6518.
Synthesis of alpha-trifluoromethyl-alpha-amino-beta-sulfone hydroxamates : novel nanomolar inhibitors of matrix metalloproteinases
S. BellostaPenultimo
;
2005
Abstract
The racemic alpha-trifluoromethyl-alpha-amino-beta-sulfone hydroxamates 1 were synthesized by means of a nucleophilic addition of sulfur-stabilized carbanions to a N-Cbz imine of trifluoropyruvate (4). The free amino derivative 1a was the most potent inhibitor of both MMP-3 (stromelysin-1) and MMP-9 (gelatinase-B), showing an IC50 = 14 nM and 1 nM, respectively, and excellent selectivity versus MMP- 1 (>5000-fold difference in inhibitory capacity). The N-Me derivative 1b was the most selective for MMP-3 with respect to MMP-9 (62-fold difference). (c) 2005 Elsevier Ltd. All rights reserved.
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