Synthesis and structure–activity relationships of a series of benzazepine derivatives as 5-HT2C receptor agonists

To identify potent and selective 5-HT2C receptor agonists, a series of novel benzazepine derivatives were synthesized, and their structure–activity relationships examined. The compounds were evaluated for their 5-HT2C, 5-HT2A, and 5-HT2B receptor binding affinity and intrinsic activity for the 5-HT2C and 5-HT2A receptors. Among these compounds, 6,7-dichloro-2,3,4,5-tetrahydro-1H-3-benzazepine (6) was effective in a rat penile erection model when administered po, which is a symptom of the serotonin syndrome reflecting 5-HT2C receptor activation. Moreover, compound 6 was characterized as a partial agonist of 5-HT2A receptors; therefore, it had little effect on the cardiovascular system.

A novel series of benzazepine derivatives was prepared, and their binding affinities for 5-HT2C, 5-HT2A, and 5-HT2B receptors were evaluated. Synthesis and structure–activity relationships, including in vivo evaluation, are discussed.Figure optionsDownload as PowerPoint slide