Structure-based design and synthesis of novel thrombin inhibitors based on phosphinic peptide mimetics

Bioorg Med Chem Lett. 1999 Jul 19;9(14):1957-62. doi: 10.1016/s0960-894x(99)00319-4.

Abstract

Based on the structure of the thrombin--NAPAP complex, phosphinic dipeptide mimetics were designed as novel thrombin inhibitors. Synthesis and evaluation of these inhibitors revealed a promising lead with an IC50 of 0.6 microM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antithrombins / chemistry*
  • Antithrombins / metabolism
  • Antithrombins / pharmacology*
  • Binding Sites
  • Computer Simulation
  • Dipeptides / chemistry
  • Dipeptides / metabolism
  • Drug Design
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Mimicry
  • Peptides / chemistry
  • Phosphinic Acids / chemistry*
  • Phosphinic Acids / metabolism
  • Phosphinic Acids / pharmacology*
  • Piperidines / chemistry
  • Piperidines / metabolism
  • Structure-Activity Relationship
  • Thrombin / chemistry
  • Thrombin / metabolism

Substances

  • Antithrombins
  • Dipeptides
  • Peptides
  • Phosphinic Acids
  • Piperidines
  • N(alpha)-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide
  • Thrombin