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.
Salameh
Bader A
BA
Organic Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden.
Leffler
Hakon
H
Nilsson
Ulf J
UJ
D002384:Catalysis; D003300:Copper / Q000737:chemistry; D015195:Drug Design; D005697:Galactosides / Q000138:chemical synthesis / Q000145:classification / Q000494:pharmacology*; D037502:Galectin 3 / Q000037:antagonists & inhibitors*; D006868:Hydrolysis; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D005697:Galactosides; D037502:Galectin 3; D003300:Copper