Discovery and SAR of small molecule PAR1 antagonists.
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.
Rilatt
Ian
I
Department of Medicinal Chemistry 4, Centre de Recherche Pierre Fabre, 17 Avenue Jean Moulin, 81106 Castres Cedex, France. Ian.Rilatt@Pierre-Fabre.com
Mirabel
Etienne
E
Le Grand
Bruno
B
Perez
Michel
M
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D044463:Receptor, PAR-1 / Q000502:physiology; D013329:Structure-Activity Relationship; D010975:Platelet Aggregation Inhibitors
C090291:C186 65; D009842:Oligopeptides; D011480:Protease Inhibitors; D044463:Receptor, PAR-1; D010975:Platelet Aggregation Inhibitors