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Regioselective alkylation of 1,3,4,5-tetrahydrobenzo[d]azepin-2-one and biological evaluation of the resulting alkylated products as potentially selective \(\hbox {5-HT}_{\mathrm{2C}}\) agonists

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Abstract

The benzazepine ring system has offered interesting CNS-active medicinal agents. Taking this privileged structure as the basic scaffold, \(\hbox {C}_{1}\) and/or \(\hbox {N}_{3}\)-alkylated benzazepin-2-one derivatives and their reduced analogs have been prepared as potential \(\hbox {5-HT}_{\mathrm{2C}}\) receptor agonists. The selective alkylation at the \(\hbox {C}_{1}\) and/or \(\hbox {N}_{3}\) positions of this seven-membered lactam ring is here reported for the first time under different reaction conditions. The synthesized compounds were evaluated for their biological profile as potential \(\hbox {5-HT}_{\mathrm{2C}}\) agonists using a classic pharmacological approach. Three derivatives (15, 17, and 20) have shown promising \(\hbox {5-HT}_{\mathrm{2C}}\) agonistic activity which can be further optimized as anti-obesity agents for the treatment of male sexual dysfunction. Further, a homology model for \(\hbox {5-HT}_{\mathrm{2C}}\) receptor was generated using MODELLER, and ligand–receptor interactions for these potential molecules were studied.

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Acknowledgments

The authors thank the Director, SAIF-Division, Panjab University, Chandigarh for their help. Navnit Prajapati, Anshuman Sinha, and Ashish M. Kanhed thank UGC, New Delhi for BSR-RFSMS-fellowship (No.F.4-1/2006 BSR/7-129/2007 BSR).

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  1. Faculty of Technology & Engineering, Kalabhavan, The M. S. University of Baroda, Vadodara, 390001, Gujarat, India

    Navnit Prajapati, Rajani Giridhar, Anshuman Sinha, Ashish M. Kanhed & Mange Ram Yadav

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  1. Navnit Prajapati
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Prajapati, N., Giridhar, R., Sinha, A. et al. Regioselective alkylation of 1,3,4,5-tetrahydrobenzo[d]azepin-2-one and biological evaluation of the resulting alkylated products as potentially selective \(\hbox {5-HT}_{\mathrm{2C}}\) agonists. Mol Divers 19, 653–667 (2015). https://doi.org/10.1007/s11030-015-9600-8

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