Thrombin receptor (PAR-1) antagonists. Solid-phase synthesis of indole-based peptide mimetics by anchoring to a secondary amide

Bioorg Med Chem Lett. 2001 Aug 20;11(16):2105-9. doi: 10.1016/s0960-894x(01)00378-x.

Abstract

A novel, 10-step, solid-phase method, based on a secondary amide linker, was developed to construct a diverse library of indole-based SFLLR peptide mimetics as thrombin receptor (protease-activated receptor 1, PAR-1) antagonists. The key steps include stepwise reductive alkylation, urea formation, and Mannich reaction. Screening of the library led to a quick development of the SAR and the significant improvement of PAR-1 activity.

MeSH terms

  • Amides / chemistry
  • Fibrinolytic Agents / chemical synthesis
  • Fibrinolytic Agents / chemistry
  • Fibrinolytic Agents / pharmacology
  • Indazoles / chemical synthesis*
  • Indazoles / chemistry
  • Indazoles / pharmacology
  • Indoles / chemistry
  • Molecular Mimicry
  • Receptors, Thrombin / antagonists & inhibitors*
  • Urea / analogs & derivatives
  • Urea / chemical synthesis*
  • Urea / chemistry
  • Urea / pharmacology

Substances

  • Amides
  • Fibrinolytic Agents
  • Indazoles
  • Indoles
  • RWJ 58259
  • RWJ-53052
  • RWJ-56110
  • Receptors, Thrombin
  • indole
  • Urea