2. Academic Validation
  3. Synthesis and antidepressant effect of novel aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7

Synthesis and antidepressant effect of novel aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7

  • Bioorg Med Chem Lett. 2019 Dec 1;29(23):126703. doi: 10.1016/j.bmcl.2019.126703.
Zheng-Song Gu 1,  Wen-Tao Wang 2,  Hao Qian 1,  Ai-Nan Zhou 1,  Hong-Bin Sun 3,  Qing-Wei Zhang 4,  Jian-Qi Li 5
Affiliations

Affiliations

  • 1 Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Shanghai 201203, PR China.
  • 2 Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Shanghai 201203, PR China; School of Engineering, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China.
  • 3 Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, PR China.
  • 4 Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Shanghai 201203, PR China. Electronic address: sipiqingwei@163.com.
  • 5 Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Shanghai 201203, PR China. Electronic address: lijianqb@126.com.
PMID: 31627993 DOI: 10.1016/j.bmcl.2019.126703
Abstract

A series of novel aralkyl piperazine and piperidine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the selective compound were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compound 19a exhibited high affinities for the 5-HT1A/5-HT7 receptors (5-HT1A, Ki = 12 nM; 5-HT7, Ki = 3.2 nM) coupled with potent serotonin reuptake inhibition (IC50 = 14 nM) and showed a marked antidepressant-like effect in the FST and TST models.

Keywords

5-HT(1A) receptor; 5-HT(7) receptor; Antidepressant; Serotonin reuptake inhibition.

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