Design and synthesis of pyridazinone-based 5-HT2C agonists

The SAR of a series of pyridazinone derived 5-HT2C agonists has been explored and resulted in identification of a compound with excellent levels of 5-HT2C functional agonism and selectivity over 5-HT2A and 5-HT2B. This compound displayed good in vivo efficacy in pre-clinical models of stress urinary incontinence, despite having physiochemical properties commensurate with impaired CNS penetration.

Graphical abstractThe design, synthesis and biological activity of pyridazinone derived, selective 5-HT2C agonists is described. Compound 24 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