Structure-Based Design of Benzimidazole Sugar Conjugates: Synthesis, SAR and In Vivo Anti-inflammatory and Analgesic Activities

Abstract

A series of 2-methyl-N-substituted-benzimidazoles, bearing hydroxypyrrolidinon-5-yl or hydroxypyrrolidin-2-yl, 2,3:5,6-di-O-isopropylidene- α-D-mannofuranoside, 2,3,5,6-tetrahydroxy-α-D-mannofuranoside, 1:2,5:6-di-O-isopropylidene-α-D-gluco-furanose,3-O-benzyl-6,7-dideoxy-1: 2-O-isopropylidene-α-D-xylo-heptofuranos-5-ulose, 3-O-benzyl-6,7-dideoxy- 1,2-dihydroxy-α-D-xylo-heptofuranos-5-ulose, 1,2,5,6-tetrahydroxy-α- D-glucofuranose sugar moieties, were obtained in good yields from 2-methyl N-(trichloroacetamidomethyl)benzimidazole as a donor and carbohydrate residues as acceptor precursors in the presence of catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as Lewis acid. Compounds 6, 7, 10, 13, 15, and 16 showed significant anti-inflammatory and analgesic activities. © 2009 Bentham Science Publishers Ltd.