Document Report Card

ID: ALA1148346

Journal: J Med Chem

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

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

Abstract: 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.

CiteXplore: 15214776

DOI: 10.1021/jm049766q