Discovery and initial structure-activity relationships of trisubstituted ureas as thrombin receptor (PAR-1) antagonists

James C. Barrow, Philippe G. Nantermet, Harold G. Selnick, Kristen L. Glass, Phung L. Ngo, Mary Beth Young, Janetta M. Pellicore, Michael J. Breslin, John H. Hutchinson, Roger M. Freidinger, Cindra Condra, Jerzy Karczewski, Rodney A. Bednar, Stanley L. Gaul, Andrew Stern, Robert Gould, Thomas M. Connolly

Research output: Contribution to journalArticlepeer-review

Abstract

Thrombin is the most potent agonist of platelet activation, and its effects are predominantly mediated by platelet thrombin receptors. Therefore, antagonists of the thrombin receptor have potential utility for the treatment of thrombotic disorders. Screening of combinatorial libraries revealed 2 to be a potent antagonist of the thrombin receptor. Modifications of this structure produced 11k, which inhibits thrombin receptor stimulated secretion and aggregation of platelets.

Original languageEnglish (US)
Pages (from-to)2691-2696
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume11
Issue number20
DOIs
StatePublished - Oct 22 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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