Retro-binding thrombin active site inhibitors: identification of an orally active inhibitor of thrombin catalytic activity

Bioorg Med Chem Lett. 2002 Nov 4;12(21):3183-6. doi: 10.1016/s0960-894x(02)00651-0.

Abstract

A series of retro-binding inhibitors of human alpha-thrombin was prepared to elucidate structure-activity relationships (SAR) and optimize in vivo performance. Compounds 9 and 11, orally active inhibitors of thrombin catalytic activity, were identified to be efficacious in a thrombin-induced lethality model in mice.

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Catalysis
  • Humans
  • Mice
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology*
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Thrombin / antagonists & inhibitors*
  • Thrombin / chemistry
  • Thrombin / toxicity

Substances

  • BMS 183507
  • GYKI-14776
  • Oligopeptides
  • Serine Proteinase Inhibitors
  • Thrombin