Structure-based design of benzimidazole sugar conjugates: synthesis, SAR and in vivo anti-inflammatory and analgesic activities.
A series of 2-methyl-N-substituted-benzimidazoles, bearing hydroxypyrrolidinon-5-yl or hydroxypyrrolidin-2-yl, 2,3:5,6-di-O-isopropylidene-alpha-D-mannofuranoside, 2,3,5,6-tetrahydroxy-alpha-D-mannofuranoside, 1:2,5:6-di-O-isopropylidene-alpha-D-gluco-furanose,3-O-benzyl-6,7-dideoxy-1:2-O-isopropylidene-alpha-D-xylo-heptofuranos-5-ulose, 3-O-benzyl-6,7-dideoxy-1,2-dihydroxy-alpha-D-xylo-heptofuranos-5-ulose, 1,2,5,6-tetrahydroxy-alpha-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.
El-Nezhawy
Ahmed O H
AO
Chemistry of Natural and Microbial Products Department, National Research Center, Dokki, Cairo, Egypt. nzhawy7@yahoo.com
Gaballah
Samir T
ST
Radwan
Mohamed A A
MA
Baiuomy
Ayman R
AR
Abdel-Salam
Omar M E
OM
D000085:Acetates / Q000494:pharmacology; D000700:Analgesics / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D002241:Carbohydrates / Q000737:chemistry*; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced; D013329:Structure-Activity Relationship
D000085:Acetates; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D001562:Benzimidazoles; D002241:Carbohydrates; C031000:benzimidazole