title: Discovery and optimization of a biphenylacetic acid series of prostaglandin D2 receptor DP2 antagonists with efficacy in a murine model of allergic rhinitis.
abstract: Biphenylacetic acid (5) was identified through a library screen as an inhibitor of the prostaglandin D(2) receptor DP2 (CRTH2). Optimization for potency and pharmacokinetic properties led to a series of selective CRTH2 antagonists. Compounds demonstrated potency in a human DP2 binding assay and a human whole blood eosinophil shape change assay, as well as good oral bioavailability in rat and dog, and efficacy in a mouse model of allergic rhinitis following oral dosing.
authors.affiliation: Amira Pharmaceuticals, 9535 Waples Street, Suite 100, San Diego, CA 92121, USA. jill.scott@amirapharm.com
authors.forename: Jill M
authors.initials: JM
authors.lastname: Scott
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: 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: Daniel S
authors.initials: DS
authors.lastname: Lorrain
authors.forename: Catherine
authors.initials: C
authors.lastname: Lee
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: Brian A
authors.initials: BA
authors.lastname: Stearns
mesh_terms: D000818:Animals; D001682:Biological Availability; D004195:Disease Models, Animal; D004285:Dogs; D055808:Drug Discovery; D051379:Mice; D010648:Phenylacetates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy*
chemical_list: D010648:Phenylacetates; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C012776:biphenylylacetic acid; C036293:prostaglandin D2 receptor