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ID: ALA1138602

Journal: Bioorg Med Chem Lett

Title: Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP(1) receptor antagonist for the treatment of inflammatory pain.

Authors: Hall A, Billinton A, Brown SH, Chowdhury A, Clayton NM, Giblin GM, Gibson M, Goldsmith PA, Hurst DN, Naylor A, Peet CF, Scoccitti T, Wilson AW, Winchester W.

Abstract: We describe the medicinal chemistry programme that led to the identification of the EP(1) receptor antagonist GSK269984A (8h). GSK269984A was designed to overcome development issues encountered with previous EP(1) antagonists such as GW848687X and was found to display excellent activity in preclinical models of inflammatory pain. However, upon cross species pharmacokinetic profiling, GSK269984A was predicted to have suboptimal human pharmacokinetic and was thus progressed to a human microdose study.

CiteXplore: 19332369

DOI: 10.1016/j.bmcl.2009.02.112