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

  • Bioorg Med Chem Lett. 2009 Aug 15;19(16):4647-51. doi: 10.1016/j.bmcl.2009.06.085.
Brian A Stearns  1 ,  Christopher Baccei ,  Gretchen Bain ,  Alex Broadhead ,  Ryan C Clark ,  Heather Coate ,  Jilly F Evans ,  Patrick Fagan ,  John H Hutchinson ,  Christopher King ,  Catherine Lee ,  Daniel S Lorrain ,  Peppi Prasit ,  Pat Prodanovich ,  Angelina Santini ,  Jill M Scott ,  Nicholas S Stock ,  Yen P Truong
Affiliations
PMID: 19608418 DOI: 10.1016/j.bmcl.2009.06.085
Abstract

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.

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