title: Synthesis and pharmacological investigation of aralkyl diamine derivatives as potential triple reuptake inhibitors.
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.
authors.affiliation: Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan No. 1 Road, Shanghai 200437, PR China.
authors.forename: Yong-Yong
authors.initials: YY
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Weng
authors.affiliation: Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan No. 1 Road, Shanghai 200437, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
authors.affiliation: Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan No. 1 Road, Shanghai 200437, PR China.
authors.forename: Mei-Yu
authors.initials: MY
authors.lastname: Zhu
authors.affiliation: Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, 1111 North Zhongshan No. 1 Road, Shanghai 200437, PR China.
authors.forename: Long-Xuan
authors.initials: LX
authors.lastname: Xing
authors.affiliation: 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.
authors.forename: Jian-Qi
authors.initials: JQ
authors.lastname: Li
mesh_terms: D000818:Animals; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D003959:Diamines; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine
keywords: Aralkyl diamine derivatives; Monoamine transporters; Triple reuptake inhibitory