DISCOVERY OF AZIRIDINE–TRIAZOLE CONJUGATES AS SELECTIVE MMP-2 INHIBITORS

Abstract

A series of (aryltriazolyl)methylaziridines was synthesized and evaluated as selective inhibitors of matrix metalloproteinase-2. They constitute a novel class of hydroxamic acidfree matrix metalloproteinase inhibitors. The triazole fragment serves as a linker between the hydrophilic aziridine and the lipophilic part of the molecule. The best inhibition was observed with 1-(aziridin-2-ylmethyl)-4-(4-butylphenyl)-1H-1,2,3-triazole and 1-(aziridin-2-ylmethyl)-4-phenyl-1H-1,2,3-triazole that selectively inhibited metalloproteinase-2 at 73% in 20 μM concentration and at 75% in 10 μM concentration, respectively.

Also published in Chemistry of Heterocyclic Compounds, 2013, 49 (8), pp 1108-1117

http://link.springer.com/article/10.1007/s10593-013-1351-9