3-(1,2,3-Triazol-1-yl)-1-thio-galactosides as small, efficient, and hydrolytically stable inhibitors of galectin-3.

Copper(I)-catalyzed addition of alkynes to methyl 3-azido-3-deoxy-1-thio-beta-D-galactopyranoside afforded stable and structurally simple 3-deoxy-3-(1H-1,2,3-triazol-1-yl)-1-thio-galactosides carrying a panel of substituents at the triazole C4 in high yields. The 3-(1H-[1,2,3]-triazol-1-yl)-1-thio-galactoside collection synthesized contained inhibitors of the tumor- and inflammation-related galectin-3 with Kd values as low as 107 microM, which is as potent as the natural disaccharide inhibitors lactose and N-acetyllactosamine.