Non-acidic pyrazole EP1 receptor antagonists with in vivo analgesic efficacy

Replacement of the carboxylic acid group in a series of previously described methylene-linked pyrazole EP1 receptor antagonists led to the discovery of amide, reversed amide and carbamate derivatives. Two compounds, 10a and 10b, were identified as brain penetrant compounds and both demonstrated efficacy in the CFA model of inflammatory pain.

Graphical abstractThis paper details the characterization of a series of amides, reversed amides and carbamates as EP1 antagonists which culminated in the identification of the two carbamate derivatives 10a and 10b. Both compounds were found to display potent analgesic activity in vivo and to penetrate the central nervous system.Figure optionsDownload full-size imageDownload as PowerPoint slide