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. Epub 2010 Dec 9.

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Disease Models, Animal
  • Dogs
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Humans
  • Inflammation / drug therapy
  • Mice
  • Phenylacetates / chemistry*
  • Phenylacetates / pharmacokinetics
  • Phenylacetates / therapeutic use
  • Pyridines / chemistry*
  • Pyridines / pharmacokinetics
  • Pyridines / therapeutic use
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / metabolism
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Receptors, Prostaglandin / metabolism

Substances

  • (2'-((cyclopropanecarbonylethylamino)methyl)-4'-(6-ethoxy-pyridin-3-yl)-6-methoxybiphenyl-3-yl)acetic acid
  • Phenylacetates
  • Pyridines
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • prostaglandin D2 receptor