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.

Graphical abstractDesign, synthesis and properties of a new tricyclic series of selective 5-HT2C receptor antagonists are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide