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1: J Med Chem. 2004 Jul 1;47(14):3491-4.Click here to read Links

Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: design, synthesis, and preclinical characterization.

Elokdah H, Abou-Gharbia M, Hennan JK, McFarlane G, Mugford CP, Krishnamurthy G, Crandall DL.

Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA. elokdah@wyeth.com

Indole oxoacetic acid derivatives were prepared and evaluated for in vitro binding to and inactivation of human plasminogen activator inhibitor-1 (PAI-1). SAR based on biochemical, physiological, and pharmacokinetic attributes led to identification of tiplaxtinin as the optimal selective PAI-1 inhibitor. Tiplaxtinin exhibited in vivo oral efficacy in two different models of acute arterial thrombosis. The remarkable preclinical safety and metabolic stability profiles of tiplaxtinin led to advancing the compound to clinical trials.

PMID: 15214776 [PubMed - indexed for MEDLINE]