306740-94-3Relevant academic research and scientific papers
Synthesis and monoamine transporter binding properties of 3α-(substituted phenyl)nortropane-2β-carboxylic acid methyl esters. Norepinephrine transporter selective compounds
Carroll, F. Ivy,Tyagi, Sameer,Blough, Bruce E.,Kuhar, Michael J.,Navarro, Hernn A.
, p. 3852 - 3857 (2007/10/03)
3α-(Substituted phenyl)nortropane-2β-carboxylic acid methyl esters (8a-h) showed high affinity for the norepinephrine transporter (NET). The most potent and selective compound was 3α-(3-fluoro-4-methylphenyl) nortropane-2β-carboxylic acid methyl ester (8d), with a Ki of 0.43 nM at the NET and 21- and 55-fold selectivity relative to binding at the dopamine and serotonin transporters. The development of 8d makes available compounds selective for all three transporters from the same structural class.
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.
Intermediates for the synthesis of radiolabelled tropanes
-
Page 26, (2008/06/13)
The compounds of the present invention comprise a tropane compound or ligand that selectively binds to tropane recognition sites, e.g., neuron transporters such as that DAT. The tropane ligand is radiolabeled with a radioactive technetium or rhenium by a chelating ligand which is attached to the tropane ligand by a linker. Tropane compounds or ligands useful in the pratice of the present invention can generally be represented by formula II where R1 and R2 are defined as above and where R1 can also be substituted at the C4 position of the tropane ring: Any tropane compound of the general formula II is useful in the present invention so long as it binds to DAT. Useful tropane analogs have a 3α-group,i.e., are of the boat configuration. Intermediates for the synthesis of the radiolabeled tropanes are claimed.
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 (2007/10/03)
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.
