5-HT2C antagonists based on fused heterotricyclic templates: design, synthesis and biological evaluation

Design, synthesis and properties of a new tricyclic series of selective 5-HT2C receptor antagonists are reported. Conformational analysis of a 2-phenyl-dihydropyrrolone scaffold suggested that ring fusion, locking coplanarity between the rings of this moiety, might be tolerated by the 5-HT2C receptor. An interesting effect of this is the change of the nature of the carbon-carbon double bond of the lactam ring from vinylic to aromatic. The changes were found to result in a favourable profile at both, receptor and in vivo level.