Reversible and Competitive Cinnamoyl Triazole Inhibitors of Tissue Transglutaminase

Abstract

A series of 15 cinnamoyl triazole derivatives was prepared by Cu(I)-catalyzed azide/alkyne [3+2]-cycloaddition reactions and examined as inhibitors of guinea-pig liver transglutaminase. Several compounds exhibited activity as reversible inhibitors that were competitive with acyl donor transglutaminase substrates. For example, triazole 4d has a K(i) value of 174 nM and represents one of the most potent reversible transglutaminase inhibitors reported to date.