title: Pyrrolovesamicols--synthesis, structure and VAChT binding of two 4-fluorobenzoyl regioisomers.
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.
authors.affiliation: Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig, Leipzig, Germany. b.wenzel@hzdr.de
authors.forename: Barbara
authors.initials: B
authors.lastname: Wenzel
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Werner
authors.initials: W
authors.lastname: Kraus
authors.forename: Dietlind
authors.initials: D
authors.lastname: Sorger
authors.forename: Osama
authors.initials: O
authors.lastname: Sabri
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000138:chemical synthesis* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004852:Epoxy Compounds / Q000737:chemistry; D005462:Fluorine Radioisotopes; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D049268:Positron-Emission Tomography; D011758:Pyrroles / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism; D014316:Tritium; D050494:Vesicular Acetylcholine Transport Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D004852:Epoxy Compounds; D005462:Fluorine Radioisotopes; D008024:Ligands; D010880:Piperidines; D011758:Pyrroles; D050494:Vesicular Acetylcholine Transport Proteins; D014316:Tritium; C006189:vesamicol; C048151:4-phenylpiperidine