Discovery of novel N-acylsulfonamide analogs as potent and selective EP3 receptor antagonists

A series of novel N-acylsulfonamide analogs were synthesized and evaluated for their binding affinity and antagonist activity for the EP3 receptor subtype. Representative compounds were also evaluated for their inhibitory effect on PGE2-induced uterine contraction in pregnant rats. Among those tested, a series of N-acylbenzenesulfonamide analogs were found to be more potent than the corresponding carboxylic acid analogs in both the in vitro and in vivo evaluations. The structure activity relationships (SAR) are also discussed.

Identification of novel N-acyl 3,4-difluorobenzenesulfonamide analogs as potent and selective EP3 receptor antagonists and their in vivo efficacy with respect to the PGE2-induced uterine contraction in pregnant rats are reported.Figure optionsDownload as PowerPoint slide