Identification and optimization of novel 1,3,4-oxadiazole EP1 receptor antagonists

A novel series of oxadiazole EP1 receptor antagonists was identified by replacing the amide of a known glycine sulfonamide derivative with a 1,3,4-oxadiazole. Optimization of the substitution patterns on the three aromatic rings led to the identification of high affinity EP1 receptor antagonists. The derivative with highest affinity displayed a binding IC50 of 2.5 nM (pIC50 8.6).

The identification of a novel series of 1,3,4-oxadiazoles is described. The SAR of the series was explored and led to the identification of the most potent compound in the series, compound 5b with a binding pIC50 value of 8.6 (IC50 2.5 nM) and a FLIPR pKi value of 8.2 (Ki 6.3 nM).Figure optionsDownload as PowerPoint slide