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.
|Titolo:||Synthesis of alpha-trifluoromethyl-alpha-amino-beta-sulfone hydroxamates : novel nanomolar inhibitors of matrix metalloproteinases|
|Autori interni:||BELLOSTA, STEFANO (Penultimo)|
|Parole Chiave:||fluorine ; matrix metalloproteinases ; inhibitors ; sulfones|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||10.1016/j.tetlet.2005.07.078|
|Appare nelle tipologie:||01 - Articolo su periodico|