Abstract
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 (IC(50)=25 and 35 nM, respectively) and to effectively block platelet aggregation induced by SFLLRN-NH(2) (TRAP-6) and alpha-thrombin.
MeSH terms
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Amines / chemistry
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Hemostatics / antagonists & inhibitors
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Hemostatics / pharmacology
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Humans
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In Vitro Techniques
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Indazoles / chemistry
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Indoles / chemical synthesis*
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Indoles / pharmacology*
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Ligands
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Molecular Mimicry
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Peptide Fragments / antagonists & inhibitors
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Peptide Fragments / pharmacology
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Platelet Aggregation / drug effects
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Receptors, Thrombin / drug effects*
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Structure-Activity Relationship
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Thrombin / antagonists & inhibitors
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Thrombin / pharmacology
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Urea / analogs & derivatives*
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Urea / chemistry
Substances
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Amines
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Hemostatics
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Indazoles
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Indoles
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Ligands
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Peptide Fragments
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RWJ-56110
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Receptors, Thrombin
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thrombin receptor peptide (42-47)
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Urea
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Thrombin