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.
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.