127648-30-0Relevant academic research and scientific papers
3alpha-(4-Substituted phenyl)nortropane-2beta-carboxylic acid methyl esters show selective binding at the norepinephrine transporter.
Blough,Holmquist,Abraham,Kuhar,Carroll
, p. 2445 - 2447 (2000)
A series of 3alpha-(4-substituted)nortropane-2beta-carboxylic acid methyl esters was synthesized and evaluated for the ability to inhibit radioligand binding at the dopamine, serotonin, and norepinephrine transporters. 3alpha-(4-Methylphenyl)nortropane-2beta-carboxylic acid methyl ester (4c) was found to be selective and highly potent for the norepinephrine transporter (NET) relative to the dopamine and serotonin transporters.
Secondary amine analogues of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid esters and N-norcocaine exhibit enhanced affinity for serotonin and norepinephrine transporters.
Boja,Kuhar,Kopajtic,Yang,Abraham,Lewin,Carroll
, p. 1220 - 1223 (1994)
N-Norcocaine (2) and six N-nor-3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid esters (4a-f) were synthesized by N-demethylation of cocaine (1) and the appropriate 3 beta-(substituted phenyl)-tropane analogues (3a-f) with alpha-chloroethyl chloroformate. Radioligand binding affinities of 2 and 4a-f at the DA, 5-HT, and NE transporter were measured and compared to those of 1 and 3a-f. N-Demethylation produced relatively small effects at the DA transporter. In contrast, 4-19-fold and 2-44-fold enhanced affinity at the serotonin and norepinephrine transporter resulted from demethylation. N-Nor-3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (4d) with an IC50 = 0.36 nM showed the greatest affinity for the serotonin transporter. However, N-nor-3 beta-(4'-ethylphenyl)tropane-2 beta-carboxylic acid methyl ester (4e) showed the greatest selectivity for the serotonin transporter.
BOLAAMPHIPHILIC COMPOUNDS, COMPOSITIONS AND USES THEREOF
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Paragraph 00444; 00445; 00446, (2016/10/31)
Bolaamphiphilic compounds are provided according to formula (I); where HG1, HG2 and L1 are as defined herein. Provided bolaamphiphilic compounds and the pharmaceutical compositions thereof are useful for delivering GDNF or NGF into animal or human brain.
Synthesis and monoamine uptake inhibition of conformationally constrained 2β-carbomethoxy-3β-phenyl tropanes
Riss, Patrick Johannes,Hummerich, Rene,Schloss, Patrick
experimental part, p. 2688 - 2698 (2009/09/07)
A series of 2β-carbomethoxy-3β-phenyl tropanes with conformationally constrained nitrogen substituents were synthesized as potential selective dopamine transporter ligands. These novel compounds were examined for their monoamine uptake inhibition potency at the human dopamine transporter (hDAT), the human serotonin transporter (hSERT) and the human noradrenalin transporter (hNET), stably expressed in human embryonic kidney cells (HEK). A SAR-study was conducted to determine the contribution of extended, 4-fluorinated, conformationally constrained C4 chains at the tropane nitrogen to human monoamine transporter affinity and selectivity. The Royal Society of Chemistry 2009.
Synthesis, structural identification, and ligand binding of tropane ring analogs of paroxetine and an unexpected aza-bicyclo[3.2.2]nonane rearrangement product
Runyon, Scott P.,Burgess, Jason P.,Abraham, Philip,Keverline-Frantz, Kathryn I.,Flippen-Anderson, Judy,Deschamps, Jeffrey,Lewin, Anita H.,Navarro, Hernan A.,Boja, John W.,Kuhar, Michael J.,Carroll, F. Ivy
, p. 2439 - 2449 (2007/10/03)
The structural requirements for high affinity at the serotonin transporter (5-HTT) have been investigated through the preparation of rigid paroxetine analogs. Tropane-derived analogs (4a-i) of paroxetine (2) were designed and synthesized as potential inhibitors of serotonin reuptake based on the structural and biological similarity between the two compound classes. Overall, the affinity of tropane-derived analogs at the 5-HTT was found to be at least an order of magnitude lower than that of paroxetine and ranged from 2-400 nM. The reduced affinity at the 5-HTT may be attributed to the inability of the rigid tropane-derived analogs to adopt conformations favored by the 5-HTT. Within the series of tropane analogs, the 2β,3β- and 2β,3α-isomers, 4a and 4d, were the most potent at the DAT and NET and are also significantly more potent than paroxetine (2) suggesting that their reduced conformational flexibility maximizes residence time in conformations favored by these transporters. Examination of the previously published preparation and structural assignment of 4a by additional NMR and X-ray crystallographic data has established that nucleophilic addition to the intermediate 2β- methanesulfonyloxymethyl-3β-(4-fluorophenyl)tropane unexpectedly provided the aza-bicyclo[3.2.2]nonane derivative 10a.
Fluoralkenyl nortropanes
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Page column 17, (2008/06/13)
Provided are compounds of the following formula: wherein R is C2-C6 mono- or multi-unsaturated hydrocarbon having one or more ethylene, acetylene or allene groups, A is 18 or 19, and X is H or halogen. The compounds of the invention bind to dopamine transporter with high affinity and selectivity and are thus useful as diagnostic and therapeutic agents for diseases associated with dopamine transporter dysfunction. The radiolabeled compounds are useful as imaging agents for visualizing the location and density of dopamine transporter by PET imaging.
Substituted 3-Phenyltropane Analogs of Cocaine: Synthesis, Inhibition of Binding at Cocaine Recognition Sites, and Positron Emission Tomography Imaging
Meltzer, P. C.,Liang, A. Y.,Brownell, A.-L.,Elmaleh, D. R.,Madras, B. K.
, p. 855 - 862 (2007/10/02)
It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3β-phenyltropane-2β-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of -3β-(4-fluorophenyl)tropane-2β-carboxylic acid methyl ester to primate caudate-putamen was evaluated. The synthesis and binding affinity of 3β-(3,4-dichlorophenyl)tropane-2β-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. The feasibility of synthesizing high-affinity ligands for cocaine recognition sites and their suitability as PET imaging ligands for cocaine receptors in vivo is demonstrated.
Synthesis and Receptor Binding of N-Substituted Tropane Derivatives. High-Affinity Ligands for the Cocaine Receptor
Milius, Richard A.,Saha, Jayanta K.,Madras, Bertha K.,Neumeyer, John L.
, p. 1728 - 1731 (2007/10/02)
The synthesis and pharmacological characterization of a series of N-substituted 3-(4-fluorophenyl)tropane derivatives is reported.The compounds displayed binding characteristics that paralleled those of cocaine, and several had substantially higher affinity at cocaine recognition sites.Conjugate addition of 4-fluorophenyl magnesium bromide to anhydroecgonine methyl ester gave 2β-(carbomethoxy)-3β-(4-fluorophenyl)tropane (4a, designated CFT, also known as WIN 35,428) after flash chromatography.N demethylation of 4a was effected by Zn/HOAc reduction of thecorresponding 2,2,2-trichloroethyl carbamate to give 2β-carbomethoxy-3β-(4-fluorophenyl)nortropane (5), which was alkylated with allyl bromide to afford the N-allyl analogue, 6.The N-propyl analogue, 7, was prepared by catalytic reduction (Pd/C) of 6.The most potent analogue, 4a, was tritiated at a specific activity of 81.3 Ci/mmol. 4a bound rapidly and reversibly to caudate putamen membranes; the two-component binding curve typical of cocaine analogues was observed.Equilibrium was achieved within 2 h and was stable for at least 4 h.High- and low-affinity Kd values observed for 4a (4.7 and 60 nM, respectively) were more than 4 times lower than those for cocaine, and the density of binding sites (Bmax = 50 pmol/g high, and 290 pmol/g, low) for the two drugs were comparable.Nonspecific binding of 4a was 5-10percent of total binding.
