2. Academic Validation
  3. Discovery of GSK345931A: An EP(1) receptor antagonist with efficacy in preclinical models of inflammatory pain

Discovery of GSK345931A: An EP(1) receptor antagonist with efficacy in preclinical models of inflammatory pain

  • Bioorg Med Chem Lett. 2009 Jan 15;19(2):497-501. doi: 10.1016/j.bmcl.2008.11.032.
Adrian Hall 1,  Susan H Brown,  Christopher Budd,  Nicholas M Clayton,  Gerard M P Giblin,  Paul Goldsmith,  Thomas G Hayhow,  David N Hurst,  Alan Naylor,  D Anthony Rawlings,  Tiziana Scoccitti,  Alexander W Wilson,  Wendy J Winchester
Affiliations

Affiliation

  • 1 Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. [email protected]
PMID: 19036582 DOI: 10.1016/j.bmcl.2008.11.032
Abstract

Herein we describe the medicinal chemistry programme to identify a potential back-up compound to the EP(1) receptor antagonist GW848687X. This work started with the lipophilic 1,2-biaryl benzene derivative 4 which displayed molecular weight of 414.9g/mol and poor in vivo metabolic stability in the rat and resulted in the identification of compound 7i (GSK345931A) which demonstrated good metabolic stability in the rat and lower molecular weight (381.9g/mol). In addition, 7i (GSK345931A) showed measurable CNS penetration in the mouse and rat and potent analgesic efficacy in acute and sub-chronic models of inflammatory pain.

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