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Eur J Med Chem. 2014 Oct 30;86:219-34. doi: 10.1016/j.ejmech.2014.08.045. Epub 2014 Aug 14.

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

Author information

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: lijianqb@126.com.

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

PMID:
25164761
DOI:
10.1016/j.ejmech.2014.08.045
[Indexed for MEDLINE]

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