Sodium [2'-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-4'- (6-ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetate (AM432): A potent, selective prostaglandin D sub(2) receptor antagonist

Compound 21 (AM432) was identified as a potent and selective antagonist of the DP sub(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 eosinoph...

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Published inBioorganic & medicinal chemistry letters Vol. 21; no. 3; pp. 1036 - 1040
Main Authors Stock, Nicholas, Volkots, Deborah, Stebbins, Karin, Broadhead, Alex, Stearns, Brian, Roppe, Jeffrey, Parr, Timothy, Baccei, Christopher, Bain, Gretchen, Chapman, Charles, Correa, Lucia, Darlington, Janice, King, Christopher, Lee, Catherine, Lorrain, Daniel S, Prodanovich, Pat, Santini, Angelina, Evans, Jilly F, Hutchinson, John H, Prasit, Peppi
Format Journal Article
LanguageEnglish
Published 01.02.2011
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Summary:Compound 21 (AM432) was identified as a potent and selective antagonist of the DP sub(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 sub(2) receptor, excellent pharmacokinetics in dog and in vivo activity in two mouse models of inflammatory disease after oral dosing.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
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ISSN:0960-894X
DOI:10.1016/j.bmcl.2010.12.016