Add time:09/03/2019 Source:sciencedirect.com
Monoamine transporters regulate the concentration of monoamine neurotransmitters, which are essential for vital physiological processes, and their dysfunction can cause several central nervous system diseases. Monoamine transporters currently appear to be the potential target in the management of these disorders. In this study, homologation and bioisosterism techniques have been used in the designing of new 1,4-disubstituted piperazines and piperidines. These derivatives were synthesized and evaluated as potential triple reuptake inhibitors for studying the structure-activity relationships. The most advanced compound, 1-(4-(5-benzhydryl-1H-tetrazol-1-yl)butyl)-4-(3-phenylpropyl)piperazine (2i), was able to inhibit monoamine neurotransmitter reuptake in an in vitro test (IC50 = 158.7 nM for 5-HT, 99 nM for NE and 97.5 nM for DA). These novel potent triple reuptake inhibitor-based 1,4-disubstituted piperazine and piperidine scaffolds deserve further systematic optimization and pharmacological evaluation.
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