2. Academic Validation
  3. Identification of novel pyrazole acid antagonists for the EP1 receptor

Identification of novel pyrazole acid antagonists for the EP1 receptor

  • Bioorg Med Chem Lett. 2006 Sep 15;16(18):4767-71. doi: 10.1016/j.bmcl.2006.06.086.
Stephen C McKeown 1,  Adrian Hall,  Gerard M P Giblin,  Olivier Lorthioir,  Richard Blunt,  Xiao Q Lewell,  Richard J Wilson,  Susan H Brown,  Anita Chowdhury,  Tanya Coleman,  Stephen P Watson,  Iain P Chessell,  Adrian Pipe,  Nick Clayton,  Paul Goldsmith
Affiliations

Affiliation

  • 1 Discovery Research, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. [email protected]
PMID: 16843659 DOI: 10.1016/j.bmcl.2006.06.086
Abstract

The discovery, synthesis and structure-activity relationship (SAR) of a novel series of EP1 receptor antagonists is described. Pyrazole acid 4, identified from a chemical array, had desirable physicochemical properties, an excellent in vitro microsomal inhibition and Cytochrome P450 (CYP450) profile and good exposure levels in blood. This compound had an ED50 of 1.3 mg/kg in a rat pain model. A range of more potent analogues in the in vitro assay was identified using efficient array chemistry. These EP1 antagonists have potential as agents in the treatment of PGE2 mediated pain.

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