Quinolizidinyl-benzimidazoles as platelet-antiaggregating agents

Chem Biodivers. 2008 May;5(5):714-28. doi: 10.1002/cbdv.200890068.

Abstract

Two series of (+/-)-2-phenyl-1-(quinolizidin-1 alpha-yl)benzimidazoles, 12A-26A, and (+/-)-2-phenyl-1-(quinolizidin-1 beta-yl)benzimidazoles, 12B-26B, were prepared and tested for the inhibition of human platelets aggregation induced by ADP, collagen, and adrenaline. All epimers A, i.e., 12A-26A, were devoid of any activity against the three agonists, while the epimers B, i.e., 12B-26B, exhibited different degrees of activity, though practically confined against the ADP-induced aggregation. The best compounds were 19B, 24B, and 26B, which inhibited for 69-67% at 260 microM and for 40-29% at 65 microM concentration the ADP (2 microM)-induced aggregation. The observed agonist and spatial structure selectivity warrant further investigations of this kind of benzimidazole derivatives.

MeSH terms

  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry*
  • Benzimidazoles / pharmacology*
  • Blood Platelets / drug effects*
  • Humans
  • Molecular Structure
  • Platelet Aggregation / drug effects*
  • Quinolizidines / chemistry*

Substances

  • Benzimidazoles
  • Quinolizidines