The discovery of 6-[2-(5-chloro-2-{[(2, 4-difluorophenyl) methyl] oxy} phenyl)-1-cyclopenten-1-yl]-2-pyridinecarboxylic acid, GW848687X, a potent and selective …

…, NM Clayton, T Coleman, A Hall, B Hammond…

Index: Giblin, Gerard M.P.; Bit, Rino A.; Brown, Susan H.; Chaignot, Helene M.; Chowdhury, Anita; Chessell, Iain P.; Clayton, Nicholas M.; Coleman, Tanya; Hall, Adrian; Hammond, Beverley; Hurst, David N.; Michel, Anton D.; Naylor, Alan; Novelli, Riccardo; Scoccitti, Tiziana; Spalding, David; Tang, Sac P.; Wilson, Alex W.; Wilson, Rich Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 2 p. 385 - 389

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Citation Number: 35

Abstract

The discovery of a series of selective EP1 receptor antagonists based on a 1, 2- diarylcyclopentene template is described. After defining the structural requirements for EP1 potency and selectivity, heterocyclic rings were incorporated to reduce logD and improve in vitro pharmacokinetic properties. The 2, 6-substituted pyridines and pyridazines gave an appropriate balance of potency, in vivo pharmacokinetic properties and a low potential for ...