title: Novel tricyclic antagonists of the prostaglandin D2 receptor DP2 with efficacy in a murine model of allergic rhinitis.
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.
authors.affiliation: Amira Pharmaceuticals, San Diego, CA 92121, USA. brian.stearns@amirapharm.com
authors.forename: Brian A
authors.initials: BA
authors.lastname: Stearns
authors.forename: Christopher
authors.initials: C
authors.lastname: Baccei
authors.forename: Gretchen
authors.initials: G
authors.lastname: Bain
authors.forename: Alex
authors.initials: A
authors.lastname: Broadhead
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Clark
authors.forename: Heather
authors.initials: H
authors.lastname: Coate
authors.forename: Jilly F
authors.initials: JF
authors.lastname: Evans
authors.forename: Patrick
authors.initials: P
authors.lastname: Fagan
authors.forename: John H
authors.initials: JH
authors.lastname: Hutchinson
authors.forename: Christopher
authors.initials: C
authors.lastname: King
authors.forename: Catherine
authors.initials: C
authors.lastname: Lee
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Lorrain
authors.forename: Peppi
authors.initials: P
authors.lastname: Prasit
authors.forename: Pat
authors.initials: P
authors.lastname: Prodanovich
authors.forename: Angelina
authors.initials: A
authors.lastname: Santini
authors.forename: Jill M
authors.initials: JM
authors.lastname: Scott
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Stock
authors.forename: Yen P
authors.initials: YP
authors.lastname: Truong
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy*
chemical_list: D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D006575:Heterocyclic Compounds, 3-Ring; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D003577:Cytochrome P-450 Enzyme System; C036293:prostaglandin D2 receptor