title: Sodium [2'-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-4'-(6-ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetate (AM432): a potent, selective prostaglandin D2 receptor antagonist.
abstract: Compound 21 (AM432) was identified as a potent and selective antagonist of the DP(2) receptor (CRTH2). Modification of a bi-aryl core identified a series of tri-aryl antagonists of which compound 21 proved a viable clinical candidate. AM432 shows excellent potency in a human whole blood eosinophil shape change assay with prolonged incubation, a comparatively long off-rate from the DP(2) receptor, excellent pharmacokinetics in dog and in vivo activity in two mouse models of inflammatory disease after oral dosing.
authors.affiliation: Amira Pharmaceuticals, 9535 Waples St., San Diego, CA 92121, USA. nickstock@gmail.com
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stock
authors.forename: Deborah
authors.initials: D
authors.lastname: Volkots
authors.forename: Karin
authors.initials: K
authors.lastname: Stebbins
authors.forename: Alex
authors.initials: A
authors.lastname: Broadhead
authors.forename: Brian
authors.initials: B
authors.lastname: Stearns
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Roppe
authors.forename: Timothy
authors.initials: T
authors.lastname: Parr
authors.forename: Christopher
authors.initials: C
authors.lastname: Baccei
authors.forename: Gretchen
authors.initials: G
authors.lastname: Bain
authors.forename: Charles
authors.initials: C
authors.lastname: Chapman
authors.forename: Lucia
authors.initials: L
authors.lastname: Correa
authors.forename: Janice
authors.initials: J
authors.lastname: Darlington
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: Pat
authors.initials: P
authors.lastname: Prodanovich
authors.forename: Angelina
authors.initials: A
authors.lastname: Santini
authors.forename: Jilly F
authors.initials: JF
authors.lastname: Evans
authors.forename: John H
authors.initials: JH
authors.lastname: Hutchinson
authors.forename: Peppi
authors.initials: P
authors.lastname: Prasit
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D010648:Phenylacetates / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011725:Pyridines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C557884:(2'-((cyclopropanecarbonylethylamino)methyl)-4'-(6-ethoxy-pyridin-3-yl)-6-methoxybiphenyl-3-yl)acetic acid; D010648:Phenylacetates; D011725:Pyridines; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C036293:prostaglandin D2 receptor