Non-covalent Thrombin Inhibitors Featuring P(3)-heterocycles With P(1)-monocyclic Arginine Surrogates

Bioorg Med Chem Lett. 2002 Apr 22;12(8):1203-8. doi: 10.1016/s0960-894x(02)00129-4.


Investigations on P(2)-P(3)-heterocyclic dipeptide surrogates directed towards identification of an orally bioavailable thrombin inhibitor led us to pursue novel classes of achiral, non-covalent P(1)-arginine derivatives. The design, synthesis, and biological activity of inhibitors NC1-NC30 that feature three classes of monocyclic P(1)-arginine surrogates will be disclosed: (1) (hetero)aromatic amidines, amines and hydroxyamidines, (2) 2-aminopyrazines, and (3) 2-aminopyrimidines and 2-aminotetrahydropyrimidines.

MeSH terms

  • Animals
  • Antithrombins / chemical synthesis
  • Antithrombins / chemistry*
  • Antithrombins / pharmacology*
  • Arginine / chemistry*
  • Dogs
  • Heterocyclic Compounds / chemistry*
  • Structure-Activity Relationship


  • Antithrombins
  • Heterocyclic Compounds
  • Arginine