Discovery and SAR of small molecule PAR1 antagonists

Ian Rilatt; Etienne Mirabel; Bruno Le Grand; Michel Perez

doi:10.1016/j.bmcl.2009.12.072

Discovery and SAR of small molecule PAR1 antagonists

Bioorg Med Chem Lett. 2010 Feb 1;20(3):903-6. doi: 10.1016/j.bmcl.2009.12.072. Epub 2009 Dec 23.

Authors

Ian Rilatt¹, Etienne Mirabel, Bruno Le Grand, Michel Perez

Affiliation

¹ Department of Medicinal Chemistry 4, Centre de Recherche Pierre Fabre, 17 Avenue Jean Moulin, 81106 Castres Cedex, France. Ian.Rilatt@Pierre-Fabre.com

PMID: 20042334
DOI: 10.1016/j.bmcl.2009.12.072

Abstract

High-throughput screening resulted in the identification of a small molecule inhibitor of PAR1. Optimisation of the initial hit led to the discovery of compounds 34 and 49, which displayed antithrombotic activity in an arteriovenous shunt model in the rat after iv administration.

Publication types

Comparative Study

MeSH terms

Animals
CHO Cells
Cricetinae
Cricetulus
Drug Discovery / methods*
Humans
Microsomes, Liver / drug effects
Microsomes, Liver / physiology
Oligopeptides / chemistry*
Oligopeptides / pharmacology*
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology
Rats
Receptor, PAR-1 / antagonists & inhibitors*
Receptor, PAR-1 / physiology
Structure-Activity Relationship

Substances

C186 65
Oligopeptides
Protease Inhibitors
Receptor, PAR-1