2. Academic Validation
  3. 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

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

  • Bioorg Med Chem Lett. 2009 May 1;19(9):2599-603. doi: 10.1016/j.bmcl.2009.02.112.
Adrian Hall 1,  Andy Billinton,  Susan H Brown,  Anita Chowdhury,  Nicholas M Clayton,  Gerard M P Giblin,  Mairi Gibson,  Paul A Goldsmith,  David N Hurst,  Alan Naylor,  Caroline F Peet,  Tiziana Scoccitti,  Alexander W Wilson,  Wendy Winchester
Affiliations

Affiliation

  • 1 Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK.
PMID: 19332369 DOI: 10.1016/j.bmcl.2009.02.112
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.

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