155337-52-3Relevant articles and documents
Synthesis of [11C]2β-Carbomethoxy-3β-(3'-iodo-4'-methyl, -ethyl and isopropyl Phenyl)Nortropane as Potential Radiotracers for Examination of the Serotonin Transporter with Positron Emission Tomography
Sandell, Johan,Halldin, Christer,Helfenbein, Julie,Chou, Yuan-Hwa,Vercouillce, Johnny,Emond, Patrick,Swahn, Carl-Gunnar,Guilloteau, Denis,Farde, Lars
, p. 1033 - 1046 (2007/10/03)
Research on depression and anxiety disorders would benefit from the development of suitable radioligands for PET-imaging of the serotonin transporter. Three cocaine analogues, 2β-carbomethoxy-3β-(3'-iodo-4'-methyl, -ethyl and isopropyl phenyl)nortropane (LBT-14, EINT and LBT-44), were prepared in a three-step synthesis by 1-4 addition of the appropriate Grignard reagent to anhydroecgonine methyl ester as first step. lodination of the phenyl ring was accomplished with a mixture of yellow mercuric oxide, perchloric acid and acetic acid followed by a solution of iodine in dichloromethane. N-desmethylation was performed by using 2,2,2-trichloroethylchloroformiate followed by treatment of zinc in acetic acid. Acidic hydrolysis of the ester functions gave the carboxylic acid analogues of LBT-14, EINT and LBT-44. The precursors were labelled with 11C using [11C]methyl iodide or [11C]methyl triflate in dimethyl formamide (DMF) and tetrabutyl ammonium hydroxide (TBAH) as base. [11C]LBT-14, [11C]EINT and [11C]LBT-44 were all examined in Cynomolgus monkey with PET. All three compounds entered the monkey brain to a high degree (ca. 5-10 percent of injected dose). There was a marked uptake of radioactivity in the thalamus and the brainstem, regions known to contain serotonin transporters. Pre-treatment with the selective serotonin transporter inhibitor citalopram had minor effect on the binding ratios, suggesting that none of the three examined radioligands are preferable to the previously examined non-iodinated 4'-isopropenyl analogue [11C]RTI-357 for the study of the serotonin reuptake system with PET.
Synthesis and transporter binding properties of 3β-(4'-alkyl-, 4'- alkenyl-, and 4'-alkynylphenyl)nortropane-2β-carboxylic acid methyl esters: Serotonin transporter selective analogs
Blough, Bruce E.,Abraham, Philip,Lewin, Anita H.,Kuhar, Michael J.,Boja, John W.,Ivy Carroll
, p. 4027 - 4035 (2007/10/03)
New methods for the synthesis of 3β-(4'-alkyl-, 4'-alkenyl-, and 4'- alkynylphenyl)nortropane-2β-carboxylic acid methyl esters 2-4, respectively, were developed. These methods involved coupling of the appropriate organometallic reagents to 3β-(4'-iodophen
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 (2007/10/02)
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.
