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

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 13, 2003, Pages 2199-2203

  Zhang, Han Cheng ^a   White, Kimberly B ^a   McComsey, David F ^a   Addo, Michael F ^a   Andrade Gordon, Patricia ^a   Derian, Claudia K ^a   Oksenberg, Donna ^a   Maryanoff, Bruce E ^a  

^a Drug Discovery   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZYL DERIVATIVE; FUNCTIONAL GROUP; INDOLE DERIVATIVE; PROTEINASE ACTIVATED RECEPTOR 1; RECEPTOR BLOCKING AGENT; THROMBIN;

ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL LINE; DRUG EFFICACY; DRUG RECEPTOR BINDING; IC 50; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; THROMBOCYTE AGGREGATION INHIBITION;

RICKETTSIA SP. PAR;

EID: 0037533957     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00325-1     Document Type: Article

References (25)

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24. The parallel improvement of potency against thrombin-induced platelet aggregation was not seen with these new analogues. The reason for the difference is not yet understood but may be related to the tether ligand situation or additional ligand-receptor interactions when thrombin is used as an agonist. All PAR-1 antagonists reported from other laboratories have generally not demonstrated parallel activities between PAR-1 receptor binding, TRAP-6-induced platelet aggregation, and thrombin-induced platelet aggregation.
25. 5-Position urea attachment was also found to be unfavorable in a different series (ref 6c).