Novel tricyclic antagonists of the prostaglandin D2 receptor DP2 with efficacy in a murine model of allergic rhinitis

Autor: Ryan C. Clark, Daniel S. Lorrain, Gretchen Bain, Jill Melissa Scott, Hutchinson John H, Alex R. Broadhead, Brian A. Stearns, Nicholas Simon Stock, Patrick Fagan, Yen Pham Truong, Angelina M. Santini, Heather Coate, Christopher Baccei, Christopher D. King, Jilly F. Evans, Catherine Lee, Peppi Prasit, Pat Prodanovich
Rok vydání: 2009
Předmět:
Zdroj: Bioorganic & Medicinal Chemistry Letters. 19:4647-4651
ISSN: 0960-894X
DOI: 10.1016/j.bmcl.2009.06.085
Popis: The synthesis of a series of tricyclic antagonists for the prostaglandin D(2) receptor DP2 (CRTH2) is disclosed. The activities of the compounds were evaluated in a human DP2 binding assay and a human whole blood eosinophil shape change assay. Potential metabolic liabilities of the compounds were addressed through in vitro CYP studies. The lead compound was demonstrated to have efficacy in a mouse model of allergic rhinitis following oral dosing.
Databáze: OpenAIRE