1. 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-HT2C agonists
- Author
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Robert B McCall, Michael D. Ennis, Nabil B Ghazal, Deborah K Hyslop, Lawrence W Fitzgerald, Dac M. Dinh, Nanette F. Nichols, Michelle L Kagey, Christopher S Knauer, Robert L Hoffman, Chris L Chio, Rebecca M. Olson, Christopher L. Haber, Kjell A. Svensson, and Jeffery E Campbell
- Subjects
Indoles ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Biochemistry ,Chemical synthesis ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,Receptor, Serotonin, 5-HT2C ,Animals ,Structure–activity relationship ,Receptor, Serotonin, 5-HT2A ,Molecular Biology ,Indole test ,Electroshock ,Organic Chemistry ,Azepines ,Serotonin Receptor Agonists ,Aggression ,Kinetics ,Template ,Anti-Anxiety Agents ,chemistry ,Drug Design ,Indoline ,Molecular Medicine ,Ataxia ,Indicators and Reagents ,Selectivity - 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.
- Published
- 2003