Active site-directed thrombin inhibitors--II. Studies related to arginine/guanidine bioisosteres

Bioorg Med Chem. 1995 Aug;3(8):1145-56. doi: 10.1016/0968-0896(95)00103-n.

Abstract

A series of N-arylsulfonylarginine amides was synthesized wherein the guanidine or arginine moiety was isosterically replaced by a number of heterocyclic functionalities. These compounds were evaluated as potential active-site inhibitors of thrombin. Bisamidines 11a-n showed a similar SAR to that of simple arginine compounds. The ex vivo clotting time measurement of 11d after ip dosing showed prolongation of clotting time in rats.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antithrombins / chemical synthesis*
  • Antithrombins / chemistry
  • Antithrombins / pharmacology
  • Arginine*
  • Binding Sites
  • Blood Coagulation / drug effects
  • Drug Design
  • Guanidines*
  • Humans
  • Indicators and Reagents
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Rats
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Thrombin / antagonists & inhibitors*

Substances

  • Antithrombins
  • Guanidines
  • Indicators and Reagents
  • Serine Proteinase Inhibitors
  • Arginine
  • Thrombin