Title of article :
1,5-Biaryl pyrrole derivatives as EP1 receptor antagonists. Structure–activity relationships of 6-substituted and 5,6-disubstituted benzoic acid derivatives
Author/Authors :
Adrian Hall، نويسنده , , Susan H. Brown، نويسنده , , Iain P. Chessell، نويسنده , , Anita Chowdhury، نويسنده , , Nicholas M. Clayton، نويسنده , , Tanya Coleman، نويسنده , , Gerard M.P. Giblin، نويسنده , , Beverley Hammond، نويسنده , , Mark P. Healy، نويسنده , , Matthew R. Johnson، نويسنده , , Ann Metcalf، نويسنده , , Anton D. Michel، نويسنده , , Alan Naylor، نويسنده , , Riccardo Novelli، نويسنده , , David J. Spalding، نويسنده , , Jennifer Sweeting، نويسنده , , Lisa Winyard، نويسنده ,
Abstract :
Herein we describe the SAR of 1,5-biaryl pyrrole derivatives, with substituents in the 6-position of the benzoic acid moiety, as EP1 receptor antagonists. Substitution at this position was well tolerated and led to the identification of several analogues with high affinity for the EP1 receptor that displayed good efficacy in the established FCA model of inflammatory pain. Furthermore, several analogues were prepared which combined substitution at the 5- and 6-positions as well as derivatives with an aromatic ring fused to the 5- and 6-positions.
