Synthesis and Evaluation of Imidazole Acetic Acid Inhibitors of Activated Thrombin-Activatable Fibrinolysis Inhibitor as Novel Antithrombotics

James C. Barrow, Philippe G. Nantermet, Shaun R. Stauffer, Phung L. Ngo, Melissa A. Steinbeiser, Shi Shan Mao, Steven S. Carroll, Carolyn Bailey, Dennis Colussi, Michelle Bosserman, Christine Burlein, Jacquelynn J. Cook, Gary Sitko, Philip R. Tiller, Cynthia M. Miller-Stein, Mark Rose, Daniel R. McMasters, Joseph P. Vacca, Harold G. Selnick

Research output: Contribution to journalArticlepeer-review

Abstract

Thrombin-activatable fibrinolysis inhibitor (TAFI) is an important regulator of fibrinolysis, and inhibitors of this enzyme have potential use in antithrombotic and thrombolytic therapy. Appropriately substituted imidazole acetic acids such as 10j were found to be potent inhibitors of activated TAFI and selective versus the related carboxypeptidases CPA, CPN, and CPM but not CPB. Further, 10j accelerated clot lysis in vitro and was shown to be efficacious in a primate model of thrombosis.

Original languageEnglish (US)
Pages (from-to)5294-5297
Number of pages4
JournalJournal of medicinal chemistry
Volume46
Issue number25
DOIs
StatePublished - Dec 4 2003
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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