130342-80-2Relevant academic research and scientific papers
Copper-mediated nucleophilic radiofluorination of [18F]β-CFT for positron emission tomography imaging of dopamine transporter
Yu, Hung-Man,Li, Ching-Yun,Liu, Shiu-Wen,Yang, Chun-Hung,Chang, Yu
, p. 228 - 236 (2021)
[18F]β-CFT is a positron emission tomography (PET) ligand for imaging of dopamine transporter. It was proved to be a sensitive PET marker to detect presynaptic dopaminergic hypofunction in Parkinson's disease. In recent years, copper-mediated 18F-fluorination of aryl boronic esters has been successful in some molecules containing aromatic groups. In this study, we describe the novel synthetic strategy of [18F]β-CFT by copper-mediated nucleophilic radiofluorination with pinacol-derived aryl boronic esters upon reaction with [18F]KF/K222 and Cu (OTf)2(py)4. The radiolabeling protocol was optimized with [18F]fluoride elution method and amount of copper catalyst used. [18F]β-CFT is obtained from boronic ester precursors in 2.2% to 10.6% non-isolated radiochemical yield (RCY). Purified [18F]β-CFT with >99% radiochemical purity (RCP) and high molar activity was obtained in validation runs. The radiolabeling procedure is straightforward and can easily be adapted for clinical use.
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 (1996)
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, radiolabeling, and preliminary in vivo evaluation of [68ga] ipcat-nota as an imaging agent for dopamine transporter
Farn, Shiou-Shiow,Chang, Kang-Wei,Lin, Wan-Chi,Yu, Hung-Man,Lin, Kun-Liang,Tseng, Yu-Chin,Chang, Yu,Yu, Chung-Shan,Lin, Wuu-Jyh
, p. 2577 - 2591 (2021/07/06)
Introduction: Novel radiotracer development for imaging dopamine transporters is a subject of interest because although [99mTc]TRODAT-1, [123I]β-CIT, and [123I]FP-CIT are commercially available;99Mo/99mTc generator is in short supply and123I production is highly dependent on compact cyclotron. Therefore, we designed a novel positron emission tomography (PET) tracer based on a tropane derivative through C-2 modification to conjugate NOTA for chelating68Ga, a radioisotope derived from a68Ge/68Ga generator. Methods: IPCAT-NOTA 22 was synthesized and labeled with [68Ga]GaCl4 ? at room tem-perature. Biological studies on serum stability, LogP, and in vitro autoradiography (binding assay and competitive assay) were performed. Furthermore, ex vivo autoradiography, biodis-tribution, and dynamic PET imaging studies were performed in Sprague Dawley rats. Results: [68Ga]IPCAT-NOTA 24 obtained had a radiochemical yield of ≥90% and a specific activity of 4.25 MBq/nmol. [68Ga]IPCAT-NOTA 24 of 85% radiochemical purity (RCP%) was stable at 37°C for up to 60 minutes in serum with a lipophilicity of 0.88. The specific binding ratio (SBR%) reached 15.8 ± 6.7 at 60 minutes, and the 85% specific uptake could be blocked through co-injection at 100-and 1000-fold of the cold precursor in in vitro binding studies. Tissue regional distribution studies in rats with [68Ga]IPCAT-NOTA 24 showed striatal uptake (0.02% at 5 minutes and 0.007% at 60 minutes) with SBR% of 6%, 25%, and 62% at 5–15, 30–40, and 60–70 minutes, respectively, in NanoPET studies. The RCP% of [68Ga]IPCAT-NOTA 24 at 30 minutes in vivo remained 67.65%. Conclusion: Data described here provide new information on the design of PET probe of conjugate/pendent approach for DAT imaging. Another chelator or another direct method of intracranial injection must be used to prove the relation between [68Ga]IPCAT-NOTA 24 uptake and transporter localization.
Method for preparing organoboron derivative containing oxygen and aromatic ring as labeled precursor of dopamine positron emission tomography imaging agent
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Paragraph 2; 4, (2021/03/04)
A method for preparing organoboron derivatives containing oxygen atoms and an aromatic ring as labeled precursors of dopamine positron emission tomography imaging agents is revealed. Hydrochloride salt of cocaine is used as an initiator. Organoboron derivatives containing oxygen atoms are directly produced on an aromatic ring as drug substances and the aromatic ring is directly labeled with radioisotope fluorine-18 (F-18). The method takes only five steps including four steps for preparing organoboron derivatives containing oxygen atoms and an aromatic ring as drug substances and a step of labeling the aromatic ring of the organoboron derivatives with F-18 directly. Not only the process time is significantly reduced, the total yield rate is also improved effectively.
Synthesis of a β-CCT-lanthanide conjugate for binding the dopamine transporter
Naumiec, Gregory R.,Lincourt, Grace,Clever, Jeremy P.,McGregor, Michael A.,Kovoor, Abraham,Deboef, Brenton
supporting information, p. 2537 - 2540 (2015/04/13)
The development of a β-CCT-lanthanide conjugate that binds the dopamine transporter (DAT) with high affinity (Kd = 303 nM) is described. Contrast agents such as the one described herein could be used as molecular probes to directly study the binding of small molecules to receptors such as DAT via MRI, PET or SPECT. This journal is
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 monoamine uptake inhibition of conformationally constrained 2β-carbomethoxy-3β-phenyl tropanes
Riss, Patrick Johannes,Hummerich, Rene,Schloss, Patrick
experimental part, p. 2688 - 2698 (2009/09/07)
A series of 2β-carbomethoxy-3β-phenyl tropanes with conformationally constrained nitrogen substituents were synthesized as potential selective dopamine transporter ligands. These novel compounds were examined for their monoamine uptake inhibition potency at the human dopamine transporter (hDAT), the human serotonin transporter (hSERT) and the human noradrenalin transporter (hNET), stably expressed in human embryonic kidney cells (HEK). A SAR-study was conducted to determine the contribution of extended, 4-fluorinated, conformationally constrained C4 chains at the tropane nitrogen to human monoamine transporter affinity and selectivity. The Royal Society of Chemistry 2009.
Novel tropane-based irreversible ligands for the dopamine transporter
Zou,Kopajtic,Katz,Wirtz,Justice Jr.,Newman
, p. 4453 - 4461 (2007/10/03)
3α-(Diphenylmethoxy)tropane (benztropine) and its analogues are tropane ring-containing dopamine uptake inhibitors that display binding and behavioral profiles that are distinct from cocaine. We previously prepared a benztropine-based photoaffinity label [125I]-(N-[4-(4′-azido-3′-iodophenyl)butyl]- 3α-[bis(4′-fluorophenyl)methoxy]tropane, [125I]1, that covalently attached to the 1-2 transmembrane spanning region of the dopamine transporter (DAT). This was in contrast to the 4-7 transmembrane spanning region labeled by a cocaine-based photoaffinity label, [125I] 2 (RTI 82). To characterize further these different binding domains, photoaffinity ligands that had the 4′-azido-3′-iodophenyl substituent extended from the same position on the tropane ring were desirable. Thus, identification of the optimal alkyl linker between this substituent and the tropane nitrogen in the benztropine series was investigated to ultimately prepare the identical N-substituted analogue of 2. In this pursuit, the N-[4-(4′-azido-3′-iodophenyl)propyl] analogue of 3α-[bis(4′-fluorophenyl)methoxy]tropane (9a) was synthesized as well as two isothiocyanate analogues that do not require photoactivation (10a,b) for irreversible binding. The synthesis of these target compounds was achieved using a modification of the strategy developed for 1. Evaluation of these compounds for displacing [3H]WIN 35 428 binding at DAT in rat caudate putamen revealed that the 4′-azido-3′-iodophenylbutyl substituent, found in 1, provided optimal binding affinity and was chosen to replace the N-CH3 group on 2. Both the 4′-azido-3′-iodophenyl- and the 4′-isothiocyanatophenylbutyl analogues of 2 (25 and 26, respectively) were synthesized. Both products bound to DAT with comparable potency (IC50 = 30 nM) to RTI 82 (2). In addition, compound 26 demonstrated wash-resistant displacement of [3H]WIN 35 428 in HEK 293 cells stably transfected with hDAT. These ligands will provide important tools for further characterizing the binding domains for tropane-based dopamine uptake inhibitors at the DAT.
Synthesis and binding affinities of 2β-(3-iodoallyloxycarbonyl)-3β-(4-substituted-aryl)tropane analogues as ligands for the dopamine transporter studies
Chung, Kyoo-Hyun,Lim, Choong Hwan,Lee, Dong Reyoul,Jin, Changbae,Chi, Dae Yoon
, p. 3077 - 3080 (2007/10/03)
Tropane analogues from cocaine, which is known to be one of the most reinforcing and addictive compounds, were designed, synthesized, and characterized for inhibition of presynaptic uptake of dopamine (DA) in brain. Eight new derivatives of 3β-aryl-2β-(3-iodoallyloxycarbonyl)tropanes were synthesized and tested for their potential abilities to displace [3H]2β-carbomethoxy-3β-(4-fluorophenyl)tropane (WIN 35,428) binding to the rat striatal membranes.
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.
