An enantioselective synthesis and biobehavioral evaluation of 7-fluoro-3-(p-fluorophenyl)-2-propyltropanes.
Optically pure 7-fluorotropanes 3a-c, were synthesized as structural probes of the dopamine transporter. The synthesis of these compounds was accomplished through the asymmetric 1,3-dipolar cycloaddition reaction of the oxidopyridinium betaine 4 with the chiral dipolarophile (R)-p-tolyl vinyl sulfoxide. In the preliminary analysis, tropane 3a was found to reduce the rewarding effects of cocaine in the brain stimulation reward paradigm.
Prakash
K R
KR
Georgetown University Medical Center, Institute for Cognitive and Computational Sciences, Washington, DC 20007-2197, USA.
Trzcinska
M
M
Johnson
K M
KM
Kozikowski
A P
AP
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001692:Biological Transport; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D015195:Drug Design; D008024:Ligands; D008454:Mazindol / Q000737:chemistry / Q000378:metabolism; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D015335:Molecular Probes; D015394:Molecular Structure; D009419:Nerve Tissue Proteins; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D012201:Reward; D012701:Serotonin / Q000378:metabolism; D014326:Tropanes / Q000138:chemical synthesis*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D015335:Molecular Probes; D009419:Nerve Tissue Proteins; D014179:Neurotransmitter Uptake Inhibitors; D014326:Tropanes; D012701:Serotonin; D008454:Mazindol; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine