Abstract
This Letter describes the synthesis of two regioisomers of a new class of vesamicol analogs as possible ligands for imaging the vesicular acetylcholine transporter in future PET studies. The two pyrrolovesamicols (±)-6a and (±)-6b were synthesized by nucleophilic ring opening reaction of a tetrahydroindole epoxide precursor with 4-phenylpiperidine. The reaction mechanism of the synthesis was studied by HPLC and the molecular structures were determined by X-ray structure analysis. Unexpected low binding affinities to VAChT (K(i)=312±73 nM for (±)-6a and K(i)=7320±1840 nM for (±)-6b) were determined by competitive binding analysis using a cell line stably transfected with ratVAChT and (-)-[(3)H]vesamicol.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Binding, Competitive
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Cell Line
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Chromatography, High Pressure Liquid
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Contrast Media / chemical synthesis*
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Contrast Media / metabolism
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Crystallography, X-Ray
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Epoxy Compounds / chemistry
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Fluorine Radioisotopes
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Humans
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Ligands
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Molecular Structure
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Piperidines / chemical synthesis*
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Piperidines / chemistry
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Piperidines / metabolism
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Positron-Emission Tomography
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Pyrroles / chemical synthesis*
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Pyrroles / metabolism
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Rats
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Stereoisomerism
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Tritium
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Vesicular Acetylcholine Transport Proteins / chemistry
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Vesicular Acetylcholine Transport Proteins / metabolism*
Substances
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Contrast Media
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Epoxy Compounds
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Fluorine Radioisotopes
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Ligands
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Piperidines
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Pyrroles
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Vesicular Acetylcholine Transport Proteins
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Tritium
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vesamicol
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4-phenylpiperidine