204071-17-0Relevant articles and documents
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
Gu, Xiao-Hui,Zong, Rushi,Kula, Nora S.,Baldessarini, Ross J.,Neumeyer, John L.
, p. 3049 - 3053 (2001)
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 β-CIT (19), the fluoroethyl ester of β-CIT (20), the N-fluoropropyl derivative of β-CBT (12), and the fluoropropyl ester of β-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 18F-labeled PET imaging agents for the DAT.
Synthesis, monoamine transporter binding, properties, and functional monoamine uptake activity of 3β-[4-methylphenyl and 4-chlorophenyl]- 2β-[5-(substituted phenyl)thiazol-2-yl]tropanes
Gong, Paul K.,Blough, Bruce E.,Brieaddy, Lawrence E.,Huang, Xiaodong,Kuhar, Michael J.,Navarro, Hernán A.,Carroll, F. Ivy
, p. 3686 - 3695 (2008/02/10)
Synthetic methods were developed for the synthesis of the 3β-(4-substituted phenyl)-2β-[5-(substituted phenyl)thiazol-2-yl] tropanes (4a-s). The compounds were evaluated for their monoamine transporter binding and monoamine uptake inhibition properties using both rat brain tissue and cloned transporter assays. In general, the compounds showed higher dopamine transporter (DAT) affinity relative to the serotonin and norepinephrine transporters (SERT and NET, respectively) and greater [3H]dopamine uptake inhibition potency relative to [3H]serotonin and [ 3H]norepinephrine uptake inhibition. Several compounds were DAT selective relative to the SERT and NET in the monoamine transporter binding assays. The most potent and selective analog in the functional monoamine uptake inhibition test was 3β-(4-methylphenyl-2β-[5-(3-nitrophenyl)thiazol-2- yl]tropane (4p).
Synthesis and binding affinities of 2β-(3-iodoallyloxycarbonyl)-3β-(4-substituted-aryl)tropane analogues as ligands for the dopamine transporter studies
Chung, Kyoo-Hyun,Lim, Choong Hwan,Lee, Dong Reyoul,Jin, Changbae,Chi, Dae Yoon
, p. 3077 - 3080 (2007/10/03)
Tropane analogues from cocaine, which is known to be one of the most reinforcing and addictive compounds, were designed, synthesized, and characterized for inhibition of presynaptic uptake of dopamine (DA) in brain. Eight new derivatives of 3β-aryl-2β-(3-iodoallyloxycarbonyl)tropanes were synthesized and tested for their potential abilities to displace [3H]2β-carbomethoxy-3β-(4-fluorophenyl)tropane (WIN 35,428) binding to the rat striatal membranes.
Synthesis, ligand binding, and quantitative structure-activity relationship study of 3β-(4'-substituted phenyl)-2β-heterocyclic tropanes: Evidence for an electrostatic interaction at the 2β-position
Kotian, Pravin,Mascarella, S. Wayne,Abraham, Philip,Lewin, Anita H.,Boja, John W.,Kuhar, Michael J.,Carroll, F. Ivy
, p. 2753 - 2763 (2007/10/03)
A set of 3β-(4'-substituted phenyl)-2β-heterocyclic tropanes was designed, synthesized, and characterized. We discovered that these compounds can function as bioisosteric replacements for the corresponding WIN 35,065-2 analogs which possess a 2β-carbometh
Cocaine and 3β-(4'-substituted phenyl)tropane-2β-carboxylic acid ester and amide analogues. New high-affinity and selective compounds for the dopamine transporter
Carroll,Kotian,Dehghani,Gray,Kuzemko,Parham,Abraham,Lewin,Boja,Kuhar
, p. 379 - 388 (2007/10/02)
Several 2β-carboxylic acid ester and amide analogues of cocaine and of 3β-(4'-substituted phenyl)tropane-2β-carboxylic acid were prepared. The binding affinities of these compounds, and of some previously prepared analogues, at the dopamine (DA), norepinephrine (NE), and serotonin (5-HT) transporters were determined. The phenyl esters of 3β-(4'-methylphenyl)and 3β-(4'-chlorophenyl)tropane-2β-carboxylic acid are highly potent and highly selective for the DA transporter. The isopropyl esters of 3β-(4'- chlorophenyl)- and 3β-(4'-iodophenyl)tropane-2β-carboxylic acid also possess high DA affinity and show significant DA transporter selectivity. Similarly, the phenyl and isopropyl ester analogues of cocaine are much more selective for the DA transporter than cocaine. Tertiary amide analogues of cocaine and of 3β-(4'-substituted phenyl)tropane-2β-carboxylic acids are more potent inhibitors of radioligand binding at the DA transporter than the primary and secondary amide analogues. In particular, 3β-(4'- chlorophenyl)tropane-2β-N-morpholinocarboxamide as well as the 3β-(4'- chlorophenyl)- and 3β-(4'-iodophenyl)tropane-2β-N-pyrrolidinocarboxamides possess high affinity and selectivity for the DA transporter. The N,N- dimethylamide cocaine analogue is the most selective cocaine amide derivative for the DA transporter. High correlation between the inhibition of radioligand binding and inhibition of uptake at the DA, NE, and 5-HT transporter was found for a selected group of analogues. Within this group, one compound, the isopropyl ester of 3β-(4'-iodophenyl)-tropane-2β- carboxylic acid, was found to be more potent in the inhibition of radioligand binding than in the inhibition of DA uptake. Taken together with its high potency and selectivity at the DA transporter, this suggests that this compound may be a lead in the development of a cocaine antagonist.
3-Aryl-2-(3'-substituted-1',2',4'-oxadiazol-5'-yl)tropane analogues of cocaine: Affinities at the cocaine binding site at the dopamine, serotonin, and norepinephrine transporters
Carroll,Gray,Abraham,Kuzemko,Lewin,Boja,Kuhar
, p. 2886 - 2890 (2007/10/02)
Previous studies have shown that 3β-(substituted phenyl)tropan-2β- carboxylic acid esters possess high affinity for the cocaine binding site on the dopamine transporter both in vitro and in vivo and inhibit dopamine uptake in vitro. Since 1,2,4-oxadiazole
