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

Roberta Sinisi, Monica Sani, Gabriele Candiani, Rachele Parente, Françoise Pecker, Stefano Bellosta, Matteo Zanda

Research output: Contribution to journalArticlepeer-review

Abstract

The racemic α-trifluoromethyl-α-amino-β-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).

Original languageEnglish
Pages (from-to)6515-6518
Number of pages4
JournalTetrahedron Letters
Volume46
Issue number38
DOIs
Publication statusPublished - Sep 19 2005

Keywords

  • Fluorine
  • Inhibitors
  • Matrix metalloproteinases
  • Sulfones

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

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