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ID: ALA1777748

Journal: Bioorg Med Chem Lett

Title: Switching between agonists and antagonists at CRTh2 in a series of highly potent and selective biaryl phenoxyacetic acids.

Authors: Luker T, Bonnert R, Schmidt J, Sargent C, Paine SW, Thom S, Pairaudeau G, Patel A, Mohammed R, Akam E, Dougall I, Davis AM, Abbott P, Brough S, Millichip I, McInally T.

Abstract: A novel series of biaryl phenoxyacetic acids was discovered as potent, selective antagonists of the chemoattractant receptor-homologous expressed on Th2 lymphocytes receptor (CRTh2 or DP2). A hit compound 4 was discovered from high throughput screening. Modulation of multiple aryl substituents afforded both agonists and antagonists, with small changes often reversing the mode of action. Understanding the complex SAR allowed design of potent antagonists such as potential candidate 34.

CiteXplore: 21592791

DOI: 10.1016/j.bmcl.2011.04.101