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

…, RL Hoffman, NB Ghazal, RM Olson, CS Knauer…

Index: Ennis, Michael D.; Hoffman, Robert L.; Ghazal, Nabil B.; Olson, Rebecca M.; Knauer, Christopher S.; Chio, Chris L.; Hyslop, Deborah K.; Campbell, Jeffery E.; Fitzgerald, Lawrence W.; Nichols, Nanette F.; Svensson, Kjell A.; McCall, Robert B.; Haber, Christopher L.; Kagey, Michelle L.; Dinh, Dac M. Bioorganic and Medicinal Chemistry Letters, 2003 , vol. 13, # 14 p. 2369 - 2372

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Citation Number: 18

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-HT2C (Ki 4.8 nM) and modest selectivity over 5-HT2A (∼ 4-fold). Several N-and C11-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.