title: Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: potential positron emission tomography (PET) imaging agents for the dopamine transporter.
abstract: A series of novel fluoroalkyl-containing tropane derivatives was synthesized, and their binding affinities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) were determined via competitive binding assays. Among these derivatives, the fluoropropyl ester of beta-CIT (19), the fluoroethyl ester of beta-CIT (20), the N-fluoropropyl derivative of beta-CBT (12), and the fluoropropyl ester of beta-CMT (18) displayed higher affinity and greater selectivity for the DAT versus SERT and NET than FP-CIT, which indicates that they are attractive candidates for the development of (18)F-labeled PET imaging agents for the DAT.
authors.affiliation: Medicinal Chemistry Laboratory, Alcohol and Drug Abuse Research Center, Belmont, MA 02478-9106, USA.
authors.forename: X H
authors.initials: XH
authors.lastname: Gu
authors.forename: R
authors.initials: R
authors.lastname: Zong
authors.forename: N S
authors.initials: NS
authors.lastname: Kula
authors.forename: R J
authors.initials: RJ
authors.lastname: Baldessarini
authors.forename: J L
authors.initials: JL
authors.lastname: Neumeyer
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004353:Drug Evaluation, Preclinical; D007457:Iodine Radioisotopes / Q000737:chemistry* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000032:analysis* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011869:Radioligand Assay; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins; D013329:Structure-Activity Relationship; D027981:Symporters / Q000032:analysis / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000379:methods*; D014326:Tropanes / Q000737:chemistry*
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; C493216:Slc6a3 protein, rat; C493232:Slc6a4 protein, rat; D027981:Symporters; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine