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

Gennady B Lapa; Gary D Byrd; Alla A Lapa; Evgeny A Budygin; Steven R Childers; Sara R Jones; Jill J Harp

doi:10.1016/j.bmcl.2005.08.028

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

Bioorg Med Chem Lett. 2005 Nov 15;15(22):4915-8. doi: 10.1016/j.bmcl.2005.08.028.

Authors

Gennady B Lapa¹, Gary D Byrd, Alla A Lapa, Evgeny A Budygin, Steven R Childers, Sara R Jones, Jill J Harp

Affiliation

¹ Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.

PMID: 16165350
DOI: 10.1016/j.bmcl.2005.08.028

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors*
Dopamine Plasma Membrane Transport Proteins / metabolism
Inhibitory Concentration 50
Molecular Structure
Piperidines / chemical synthesis*
Piperidines / chemistry
Piperidines / pharmacology*
Structure-Activity Relationship

Substances

Dopamine Plasma Membrane Transport Proteins
Piperidines

Grants and funding

AA014091/AA/NIAAA NIH HHS/United States