title: 2,3,4,5-tetrahydro- and 2,3,4,5,11,11a-hexahydro-1H-[1,4]diazepino[1,7-a]indoles: new templates for 5-HT(2C) agonists.
abstract: The design and synthesis of the novel 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole 5 is described. This azepinoindole has excellent affinity for 5-HT(2C) (K(i) 4.8 nM) and modest selectivity over 5-HT(2A) ( approximately 4-fold). Several N- and C(11)-substituted analogues of 5 were prepared, as were a number of biaryl indoline derivatives. The anxiolytic potential for the azepinoindole template 5 is demonstrated by activity in a mouse shock-aggression assay.
authors.affiliation: Medicinal Chemistry III, Pharmacia Corporation, 301 Henrietta Street, 49009, Kalamazoo, MI, USA. d.ennis@pharmacia.com
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ennis
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hoffman
authors.forename: Nabil B
authors.initials: NB
authors.lastname: Ghazal
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Olson
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Knauer
authors.forename: Chris L
authors.initials: CL
authors.lastname: Chio
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Hyslop
authors.forename: Jeffery E
authors.initials: JE
authors.lastname: Campbell
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Fitzgerald
authors.forename: Nanette F
authors.initials: NF
authors.lastname: Nichols
authors.forename: Kjell A
authors.initials: KA
authors.lastname: Svensson
authors.forename: Robert B
authors.initials: RB
authors.lastname: McCall
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Haber
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Kagey
authors.forename: Dac M
authors.initials: DM
authors.lastname: Dinh
mesh_terms: D000374:Aggression / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001259:Ataxia / Q000139:chemically induced; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D004597:Electroshock; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C481399:2,3,4,5,11,11a-hexahydro-1H-(1,4)diazepino(1,7-a)indole; C481398:2,3,4,5-tetrahydro-1H-(1,4)diazepino(1,7-a)indole; D014151:Anti-Anxiety Agents; D001381:Azepines; D007202:Indicators and Reagents; D007211:Indoles; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017366:Serotonin Receptor Agonists