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

  • Bioorg Med Chem Lett. 2011 Feb 1;21(3):1036-40. doi: 10.1016/j.bmcl.2010.12.016.
Nicholas Stock  1 ,  Deborah Volkots ,  Karin Stebbins ,  Alex Broadhead ,  Brian Stearns ,  Jeffrey Roppe ,  Timothy Parr ,  Christopher Baccei ,  Gretchen Bain ,  Charles Chapman ,  Lucia Correa ,  Janice Darlington ,  Christopher King ,  Catherine Lee ,  Daniel S Lorrain ,  Pat Prodanovich ,  Angelina Santini ,  Jilly F Evans ,  John H Hutchinson ,  Peppi Prasit
Affiliations
PMID: 21211969 DOI: 10.1016/j.bmcl.2010.12.016
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.