title: 5-HT2C antagonists based on fused heterotricyclic templates: design, synthesis and biological evaluation.
abstract: 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.
authors.affiliation: GlaxoSmithKline, Medicine Research Centre, Via Fleming, 4, 37135 Verona, Italy. dieter.w.hamprecht@gsk.com
authors.forename: Dieter
authors.initials: D
authors.lastname: Hamprecht
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Micheli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tedesco
authors.forename: Daniele
authors.initials: D
authors.lastname: Donati
authors.forename: Marcella
authors.initials: M
authors.lastname: Petrone
authors.forename: Silvia
authors.initials: S
authors.lastname: Terreni
authors.forename: Martyn
authors.initials: M
authors.lastname: Wood
mesh_terms: D000478:Alkylation; D000818:Animals; D001682:Biological Availability; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D044403:Receptor, Serotonin, 5-HT2B / Q000187:drug effects; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists