2. Academic Validation
  3. Synthesis and pharmacological investigation of aralkyl diamine derivatives as potential triple reuptake inhibitors

Synthesis and pharmacological investigation of aralkyl diamine derivatives as potential triple reuptake inhibitors

  • Eur J Med Chem. 2014 Oct 30:86:219-34. doi: 10.1016/j.ejmech.2014.08.045.
Yong-Yong Zheng 1,  Zhi-Jie Weng 2,  Peng Xie 1,  Mei-Yu Zhu 1,  Long-Xuan Xing 1,  Jian-Qi Li 3
Affiliations

Affiliations

  • 1 Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan No. 1 Road, Shanghai 200437, PR China.
  • 2 Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan No. 1 Road, Shanghai 200437, PR China; School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, PR China.
  • 3 Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan No. 1 Road, Shanghai 200437, PR China. Electronic address: [email protected].
PMID: 25164761 DOI: 10.1016/j.ejmech.2014.08.045
Abstract

A series of aralkyl diamine derivatives were designed, synthesized, and evaluated for their triple reuptake inhibitory abilities. Compounds 18c (5-HT, NE, DA, IC50 = 389, 69, 238 nM), 36a (5-HT, NE, DA, IC50 = 378, 477, 247 nM), and 36d (5-HT, NE, DA, IC50 = 501, 206, 357 nM) showed in vivo activities in the rat forced swim test at 5, 10, and 20 mg/kg PO. 36a was identified as the most promising candidate in this study. Specifically, 36a exhibited high selectivity for monoamine transporters over a number of CNS-related targets. Furthermore, 36a showed a good pharmacokinetic properties and acceptable safety profile in preclinical studies.

Keywords

Aralkyl diamine derivatives; Monoamine transporters; Triple reuptake inhibitory.

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