Selective 3-amino-2-pyridinone acetamide thrombin inhibitors incorporating weakly basic partially saturated heterobicyclic P1-arginine mimetics

Bioorg Med Chem Lett. 2003 Oct 6;13(19):3171-6. doi: 10.1016/s0960-894x(03)00717-0.

Abstract

Novel, highly selective and potent thrombin inhibitors were identified as a result of combing the 3-benzylsulfonylamino-2-pyridinone acetamide P(2)-P(3) surrogate with weakly basic partially saturated heterobicyclic P(1)-arginine mimetics 1-8. The design, synthesis, biological activity, and the binding modes of non-covalent thrombin inhibitors featuring P(1)-4,5,6,7-tetrahydroindazole, 5,6,7,8-tetrahydroquinazoline, and 4,5,6,7-tetrahydrobenzothiazole moieties are described.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemistry*
  • Acetamides / pharmacology
  • Antithrombins / chemistry*
  • Antithrombins / pharmacology
  • Arginine / chemistry*
  • Arginine / pharmacology
  • Humans
  • Piperidones / chemistry*
  • Piperidones / pharmacology
  • Pyridones / chemistry*
  • Pyridones / pharmacology
  • Thrombin / antagonists & inhibitors
  • Thrombin / chemistry

Substances

  • 3-aminopiperidine-2-one
  • Acetamides
  • Antithrombins
  • Piperidones
  • Pyridones
  • Arginine
  • Thrombin