Design and synthesis of piperazinylpyrimidinones as novel selective 5-HT2C agonists

This Letter reports the design and synthesis of several novel series of piperazinyl pyrimidinones as 5-HT2C agonists. Several of the compounds presented exhibit good in vitro potency and selectivity over the closely related 5-HT2A and 5-HT2B receptors. Compound 11 was active in in vivo models of stress urinary incontinence.

Graphical abstractThe design, synthesis and biological activity of several novel series of piperazinyl pyrimidinones is described. Compound 11 showed efficacy in a pre-clinical model of urethral function which highlights potential efficacy in stress urinary incontinence.Figure optionsDownload full-size imageDownload as PowerPoint slide