کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1398850 | 1501130 | 2014 | 16 صفحه PDF | دانلود رایگان |
• A series of aralkyl diamine derivatives were designed and synthesized.
• Target compounds were tested for triple reuptake inhibition.
• Three lead compounds showed in vivo activities in the rat forced swim test.
• 36a displayed desirable pharmacokinetic properties, and acceptable safety profile.
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.
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Journal: European Journal of Medicinal Chemistry - Volume 86, 30 October 2014, Pages 219–234