Tetrahydroquinoline-based tricyclic amines as potent and selective agonists of the 5-HT receptor.

The syntheses, structure-activity relationships (SARs), and biological activities of tetrahydroquinoline-based tricyclic amines as 5-HT receptor agonists are reported. An early lead containing a highly unique 6,6,7-ring system was optimized for both in vitro potency and selectivity at the related 5-HT receptor. Orally bioactive, potent, and selective 6,6,6-tricyclic 5-HT agonists were identified.