High-affinity thrombin receptor (PAR-1) ligands: A new generation of indole-based peptide mimetic antagonists with a basic amine at the C-terminus

Article abstract of DOI:10.1016/S0960-894X(03)00325-1

A new generation of indole-based peptide mimetics, bearing a basic amine at the C-terminus, was developed by the agency of two complementary, multistep, trityl resin-based approaches. Thus, we obtained several high-affinity thrombin receptor (PAR-1) ligands, such as 32 and 34. Compounds 32 and 34 were found to bind to PAR-1 with excellent affinity (IC₅₀=25 and 35 nM, respectively) and to effectively block platelet aggregation induced by SFLLRN-NH₂ (TRAP-6) and α-thrombin.