50370-57-5Relevant academic research and scientific papers
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 (1991)
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.
Design, synthesis and biological evaluation of 7-azatricyclodecanes: Analogues of cocaine
Tamiz, Amir P.,Smith, Miles P.,Kozikowski, Alan P.
, p. 297 - 300 (2007/10/03)
The synthesis and biological activity of a series of azatricyclodecane analogues of cocaine are described. All compounds studied in this series exhibit nanomolar potency and good selectivity for the serotonin transporter versus the dopamine transporter. (
Isomerization study of aryltropane analogs of cocaine
Zheng, Qi-Huang,Mulholland, G. Keith
, p. 333 - 340 (2007/10/03)
Isomerization of brain imaging agents aryltropane cocaine analogs have been examined by HPLC under chemical conditions similar to those encountered during radiolabeling.
Stereoselective synthesis of 2β-carbomethoxy-3β-phenyltropane derivatives. Enhanced stereoselectivity observed for the conjugate addition reaction of phenylmagnesium bromide derivatives with anhydro dichloromethane
Xu,Trudell
, p. 2037 - 2039 (2007/10/03)
The use of dichloromethane as a solvent for the conjugate addition reaction of preformed etheral solutions of phenylmagnesium bromide derivatives with anhydroecgonine methyl ester (2) was found to enhance the stereoselectivity of the reaction and provide the 2β-carbemethoxy-3β-phenyltropane derivatives 3a-d in high yield.
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.
