Solubilized phenyl-pyrazole ureas as potent, selective 5-HT(2A) inverse-agonists and their application as antiplatelet agents

Peter I Dosa; Sonja Strah-Pleynet; Honnappa Jayakumar; Martin Casper; Marc Decaire; Yifeng Xiong; Juerg Lehmann; Karoline Choi; Katie Elwell; Amy Wong; Robert R Webb; John W Adams; Juan Ramirez; Jeremy G Richman; William Thomsen; Graeme Semple; Bradley R Teegarden

doi:10.1016/j.bmcl.2009.07.073

Solubilized phenyl-pyrazole ureas as potent, selective 5-HT(2A) inverse-agonists and their application as antiplatelet agents

Bioorg Med Chem Lett. 2009 Sep 15;19(18):5486-9. doi: 10.1016/j.bmcl.2009.07.073. Epub 2009 Jul 18.

Authors

Peter I Dosa¹, Sonja Strah-Pleynet, Honnappa Jayakumar, Martin Casper, Marc Decaire, Yifeng Xiong, Juerg Lehmann, Karoline Choi, Katie Elwell, Amy Wong, Robert R Webb, John W Adams, Juan Ramirez, Jeremy G Richman, William Thomsen, Graeme Semple, Bradley R Teegarden

Affiliation

¹ Arena Pharmaceuticals Inc., 6166 Nancy Ridge Drive, San Diego, CA 92121, United States. pidosa@umn.edu

PMID: 19665894
DOI: 10.1016/j.bmcl.2009.07.073

Abstract

Potent 5-HT(2A) inverse-agonists containing phenyl-pyrazole ureas with an amino side chain were identified. Optimization of this series resulted in selective compounds that proved effective in modulating 5HT-induced amplification of ADP-stimulated human platelet aggregation.

MeSH terms

Humans
Platelet Aggregation / drug effects
Platelet Aggregation Inhibitors / chemistry*
Platelet Aggregation Inhibitors / pharmacology*
Pyrazoles / chemistry
Pyrazoles / pharmacology
Receptor, Serotonin, 5-HT2A / metabolism
Serotonin 5-HT2 Receptor Agonists*
Structure-Activity Relationship
Urea / analogs & derivatives*
Urea / pharmacology*

Substances

Platelet Aggregation Inhibitors
Pyrazoles
Receptor, Serotonin, 5-HT2A
Serotonin 5-HT2 Receptor Agonists
pyrazole
Urea