Design and synthesis of potent and selective macrocyclic thrombin inhibitors

Philippe G. Nantermet, James C. Barrow, Christina L. Newton, Janetta M. Pellicore, Mary Beth Young, S. Dale Lewis, Bobby J. Lucas, Julie A. Krueger, Daniel R. McMasters, Youwei Yan, Lawrence C. Kuo, Joseph P. Vacca, Harold G. Selnick

Research output: Contribution to journalArticlepeer-review

Abstract

A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity.

Original languageEnglish (US)
Pages (from-to)2781-2784
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume13
Issue number16
DOIs
StatePublished - Aug 18 2003
Externally publishedYes

ASJC Scopus subject areas

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

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