50370-57-5Relevant articles and documents
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. (
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.
