Dual DAT/sigma1 Receptor Ligands Based on 3-(4-(3-(bis(4-fluorophenyl)amino)propyl)piperazin-1-yl)-1-phenylpropan-1-ol

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2008 Sep 9

PMID 18774292

Citations 6

Authors

Jianjing Cao

Theresa Kopajtic

Jonathan L Katz

Amy Hauck Newman

Affiliations

Soon will be listed here.

Abstract

Ester analogs of (+/-)3-(4-(3-(bis(4-fluorophenyl)amino)propyl)piperazin-1-yl)-1-phenylpropan-1-ol were synthesized and evaluated for binding at DAT, SERT, NET, and sigma1 receptors, and compared to GBR 12909 and several known sigma1 receptor ligands. Most of these compounds demonstrated high affinity (K(i)=4.3-51 nM) and selectivity for the DAT among the monoamine transporters. S- and R-1-(4-(3-(bis(4-fluorophenyl)amino)propyl)piperazin-1-yl)-3-phenylpropan-2-ol were also prepared wherein modest enantioselectivity was demonstrated at the DAT. However, no enantioselectivity at sigma1 receptors was observed and most of the ester analogs of the more active S-enantiomer showed comparable binding affinities at both DAT and sigma1 receptors with a maximal 16-fold DAT/sigma1 selectivity.

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