173830-21-2Relevant academic research and scientific papers
Synthesis of novel halo and tosyloxy nortropane derivatives as efficient precursors for the one-step synthesis of the dopamine transporter PET ligand [18F]FECNT
Pijarowska-Kruszyna,Jaron,Kachniarz,Kasprzak,Kowalska,Malkowski,Demphel,Dolle,Mikolajczak
, p. 148 - 157 (2014/04/03)
The fluorine-18 labeled nortropane derivative 2β-carbomethoxy-3β- (4-chlorophenyl)-8-(2-fluoroethyl)-nortropane (FECNT) is a dopamine transporter (DAT) ligand. Currently, it is considered as reference for positron emission tomography imaging. Herein, the synthesis of novel precursors (N-tosyloxy-, chloro-, and bromo- analogues) for one-step radiosynthesis of [ 18F]FECNT is reported. Using the N-mesyloxy- precursor in a one-step radiosynthesis, the crude [18F]FECNT was obtained with the radiolabeling yield of 45 ± 10%, confirming the practical efficiency of this approach in the design of novel precursors for labeling. Copyright
Synthesis and 11C-Radiolabelling of a Tropane Derivative Lacking the 2β Ester Group: A Potential PET-Tracer for the Dopamine Transporter
Schoenbaechler, Roland,Ametamey, Simon M.,Schubiger, Pius A.
, p. 447 - 456 (2007/10/03)
The synthesis and 11C-radiolabelling of a new tropane analogue, 3β-(4'-chlorophenyl)-2β-(3'-phenylisoxazol-5'-yl)tropane (β-CPPIT), an inhibitor of the dopamine transporter, is reported. The desmethyl compound, 3β-(4'-chlorophenyl)-2β-(3'-phenylisoxazol-5'-yl)nortropane (5) was prepared via a six-step reaction sequence starting from cocaine. [11C]-β-CPPIT was labelled by N-methylation using [11C]-methyl iodide obtained from the gas phase reaction of [11C]-methane with iodine in 60 +/- 10 percent radiochemical yield (decay corrected from [11C]-methyl iodide). The overall synthesis time was on average 60 minutes at EOB (end of bombardment). The final product had a specific activity of 2000 - 2700 Ci/mmol (74 - 100 TBq/mmol) at EOS (end of synthesis) and the radiochemical purity was greater than 99 percent. [11C]-β-CPPIT showed a logP value of 2.1 indicating that a free diffusion through the blood-brain-barrier should be possible.
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.
Synthesis and characterization of radioiodinated N-(3-iodopropen-1-yl)- 2β-carbomethoxy-3β-(4-chlorophenyl)tropanes: Potential dopamine reuptake site imaging agents
Goodman,Kung,Kabalka,Kung,Switzer
, p. 1535 - 1542 (2007/10/02)
Methods have been developed for the preparation of radioiodinated N- substituted 2β-carbomethoxy-3β-(4-chlorophenyl)tropanes. The syntheses, physical properties, radiolabeling, and characterization of the pharmacological properties of N-(3(Z)-iodopropen-1-yl)-2β-carbomethoxy-3β- (4-chlorophenyl)tropane (12) and N-(3(E)-iodopropen-1-yl)-2β-carbomethoxy- 3β-(4-chlorophenyl)tropane (13) are described. 2β-Carbomethoxy-3β-(p- substituted-phenyl)tropanes are potent ligands for the dopamine transporter. The radioiodinated derivatives are of interest because of the high uptake and prolonged striatal retention that may result from specific binding to low- capacity, high-affinity, dopamine reuptake sites. Radioiodine was introduced into the 3Z and 3E-position of N-(3-iodopropen-1-yl)-2β-carbomethoxy-3β- (4-chlorophenyl)tropane by iododemetalation of the corresponding 3-(tri-n- butylstannyl) derivatives. Competition binding data of various dopamine reuptake ligands with rat striatal tissue preparation for either [125I]- 12 or [125I]-13 exhibited the following order of potency: E-13 > Z-12 > GBR 12909 >> mazindol >>> (-)-cocaine. Tissue distribution studies in rats showed that the E-13 was the best analogue. E-13 showed high striatal uptake (60 min, 1.23% dose/g; 120 min, 0.61% dose/g) and high striatal to cerebellum ratios (60 min, 15.9/1; 120 min, 16.5/1). These studies indicate that iodine- 123-labeled E-13 is a potentially useful agent for imaging the dopamine reuptake sites by single-photon-emission computerized tomography.
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.
