Structure-based design of benzimidazole sugar conjugates: synthesis, SAR and in vivo anti-inflammatory and analgesic activities

Med Chem. 2009 Nov;5(6):558-69. doi: 10.2174/157340609790170461.

Abstract

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.

MeSH terms

  • Acetates / pharmacology
  • Analgesics / adverse effects
  • Analgesics / chemistry
  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / chemistry
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Benzimidazoles / adverse effects
  • Benzimidazoles / chemistry*
  • Benzimidazoles / pharmacology*
  • Benzimidazoles / therapeutic use
  • Carbohydrates / chemistry*
  • Drug Design*
  • Edema / chemically induced
  • Edema / drug therapy
  • Mice
  • Rats
  • Stomach Ulcer / chemically induced
  • Structure-Activity Relationship

Substances

  • Acetates
  • Analgesics
  • Anti-Inflammatory Agents
  • Antidepressive Agents
  • Benzimidazoles
  • Carbohydrates
  • benzimidazole