Design and synthesis of pyridazinone-based 5-HT2C agonists

The SAR of a series of pyridazinone derived 5-HT 2C agonists has been explored and resulted in identification of a compound with excellent levels of 5-HT 2C functional agonism and selectivity over 5-HT 2A and 5-HT 2B . This compound displayed good in vivo efficacy in pre-clinical models of stress urinary incontinence, despite having physiochemical properties commensurate with impaired CNS penetration.