Synthesis and monoamine transporter affinity of 2beta-carbomethoxy-3beta-(4'-p-substituted phenyl)-piperidine analogs of cocaine.
A series of novel piperidine based analogs of cocaine was synthesized and evaluated in vitro against the three monoamine transporters to develop new potential selective SERT radiotracers. Modification of the phenyl substitution with five-membered heterocyclic groups resulted in a wide affinity and selectivity scale. Radiolabeling and mouse in vivo study was performed on the piperidine analog of ZIENT, which crossed the blood-brain barrier but failed to selectively accumulate in the regions of the brain rich in SERT.
Bois
Frederic
F
Yale University, School of Medicine, VA Connecticut HCS, 116A2, 950 Campbell Avenue, 06516, USA.
Baldwin
Ronald M
RM
Kula
Nora S
NS
Baldessarini
Ross J
RJ
Al Tikriti
M
M
Innis
Robert B
RB
Tamagnan
Gilles D
GD
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D051379:Mice; D050479:Neurotransmitter Transport Proteins / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011849:Radioactive Tracers; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014326:Tropanes
D050483:Dopamine Plasma Membrane Transport Proteins; D050479:Neurotransmitter Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010880:Piperidines; D011849:Radioactive Tracers; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D014326:Tropanes; D003042:Cocaine