The synthesis and biological evaluation of dopamine transporter inhibiting activity of substituted diphenylmethoxypiperidines

The synthesis of potent 4-aryl methoxypiperidinol inhibitors of the dopamine transporter is described. Symmetrical para substituents of the benzene rings are important for high potency in binding to the dopamine transporter. 4-[Bis(4-fluorophenyl) methoxy]-1-methylpiperidine has an IC50 of 22.1 ± 5.73 nM and increases locomotor activity in mice.

Graphical abstractThe development of potent 4-(arylmethoxy)-1-alkylpiperidine inhibitors of the dopamine transporter is described. Symmetrical para substituents of the benzene rings are important for high potency in binding to the dopamine transporter. 3b has an IC50 = 22.1 ± 5.73 nM and elevates locomotor activity in mice, 3g has an IC50 = 12.1 ± 7.51 nM and is inactive in this test.Figure optionsDownload full-size imageDownload as PowerPoint slide