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The title compound tetrabenazine was synthesized by reaction of 3-dimethyl-aminomethylheptan-2-one and 6,7-dimethoxy-3,4-dihydroisoquinoline hydrochloride. This approach provides an efficient and concise way to the synthesis of the marketed drug tetrabenazine. The colorless single crystal of tetrabenazine suitable for X-ray analysis was obtained fr...
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... If it consists of diastereomers, in the 1 H NMR spectrum of TBZ, the two benzene ring proton resonances at C-8 and C-11, as shown in Fig. 1, will split into multiple peaks, rather than two singlet peaks. This can be indirectly confirmed from the literature [10]. The two benzene ring proton resonances in TBZ synthesized by our team are shown in Fig. 6. There are two singlet peaks. By this means, we can determine that our TBZ consists of (3R, 11bR) and (3S, 11bS) enantiomers or (3R, 11bS) and (3S, 11bR) enantiomers. The X-ray diffraction of the single crystal chosen from TBZ's saturated methanol solution indicated that the precipitated crystal contains (3R, 11bR) and (3S, 11bS) ...
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... .O van der Waals interaction between them. The packing diagram of 2 are presented in Fig. S8 and is stabilized, in addition to the covalent bonds, by the homo-interaction of benzene rings of adjacent biphen ligands from an adjacent chain, through p-p stacking, the centroid-centroid distance being within the limit of p-p interaction of the aromatic rings [49] whereas hetero-interaction between the pyridyl ring of the tmdp ligand and the phenyl ring of the biphen ligand is not possible due to a large centroidcentroid distance of 6.596 Å between them [50]. ...
Two novel Zn(II) coordination polymers (CPs), [Zn(nba) 2 (tmdp)] n (1) and [Zn(biphen) 2 (tmdp)] n (2), were synthesised by reacting Zn(NO 3) 2 Á6H 2 O and 4,4 0-trimethylenedipyridine (tmdp) with corresponding car-boxylates: 4-nitrobenzoic (Hnba) and 4-biphenylcarboxylic acid (Hbiphen). Their structures were characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD) and single-crystal X-ray diffraction. Compounds 1 and 2 are one-dimensional CPs with the zinc(II) carboxylate units bridged through the N-donor spacer ligand. The zinc (II) atom adopts a tetrahedral arrangement in 1 and 2 coordinated by two nitrogen atoms from two tmdp ligand molecules and two deprotonated oxygen atoms from two carboxylate ligand molecules. The adsorption capacities of MO in this study was found to be 546.31 mg/g and 22.67 mg/g for 1 and 2, respectively. DFT studies confirmed that adsorption is primarily due to p-p stacking and electrostatic interactions between MO and 1. It is noteworthy that binding energy (BE) values for 1 (-74.14 KJ/mol) and 2 (-61.11 KJ/mol) correlate reasonably well with the observed adsorption capacities of MO. The study demonstrated that 1 has higher adsorption efficiency in comparison to 2 and could be an effective and easily reusable adsorbent for the removal of MO from wastewater.
... Our earlier work on using 1 H NMR to determine the composition of tetrabenazine (TBZ) could be used to confirm this point. 20 If compound 5 consisted of diastereomers, in the 1 H NMR spectrum of compound 5, the two aromatic ring proton resonances at C-8 and C-11 (the numbered compound 5 shown in Scheme 2) would split into multiple peaks, rather than two singlet peaks. The two aromatic ring proton resonances in compound 5 were two singlet peaks. ...
This article reports, for the first time, on the absolute configuration of (+)-9-benzyloxy-α-dihydrotetrabenazine (8), as determined from the perspective of X-ray crystallography. Compound 8 was prepared by a six-step reaction using 3-benzyloxy-4-methoxybenzaldehyde (1) as a starting material. The X-ray crystal diffraction structure of two compounds, racemic 9-benzyloxy-tetrabenazine (5) and the diastereomeric salt of compound 8, is also described for the first time in this article. The X-ray results and the chiral HPLC helped elucidate that compound 8 has an absolute configuration as 2R,3R,11bR. The crystal structure of racemic compound 5 contains two symmetry- independent molecules in the unit cell. Interestingly, while they are structural isomers, they are enantiomers, too, i.e., in solution, because they are not mirror images of each other in the crystal lattice. In order to elucidate the intermolecular interaction mechanism of the diastereomeric salt of compound 8, its crystal packing was investigated with regard to the weak interactions, such as salt bridge, OH…O and CH…O hydrogen bonds, and intermolecular CH…π interaction. The results showed that the carbonyl-assisted salt bridges and the OH…O hydrogen bonds formed polar columns in the crystal structure of the diastereomeric salt of compound 8, resembling butterflies with open wings as viewed along the c-axis. These polar columns were extended to three-dimensional network by intermolecular CH…O hydrogen bonds and intermolecular CH…π interactions. Chirality, 2013. © 2013 Wiley Periodicals, Inc.
The development of technetium-99m-labelled dihydrotetrabenazine (DTBZ) derivatives for vesicular monoamine transporter 2 (VMAT2) tracing could be a benefit for single photon emission computed tomography (SPECT) imaging due to easy labelling chemistry and great availability through nuclide generator system. Here, we successfully prepared a technetium-99m-labelled DTBZ derivative and subsequently evaluated its biological activity targeting VMAT2. A novel combination of the bisaminoethanethiol (BAT) chelator scaffold with the biologically active DTBZ vector was performed to synthesize the labelling precursor BAT-P-DTBZ, and it was accomplished in six steps. The technetium-99m labelling was carried out in the radiochemical study of BAT-P-DTBZ conjugate, and the radiolabelling conditions were investigated and optimized. Under the optimized labelling condition, 99mTc-BAT-P-DTBZ was acquired with a good radiochemical purity of above 95%. The quality control test showed that 99mTc-BAT-P-DTBZ is stable over 6 h and it has a suitable lipophilicity, suggesting successful appositeness for the needs of routine biological evaluation experiments. The in vitro biological evaluation revealed that 99mTc-BAT-P-DTBZ could bind to VMAT2 sites. The in vivo biodistribution study clearly indicated that the pancreas (VMAT2-enriched region) displayed relatively high uptake of 99mTc-BAT-P-DTBZ among all organs in mice. The specific VMAT2 binding signal of 99mTc-BAT-P-DTBZ was separately detected in the in vitro and in vivo biological evaluation. Therefore, 99mTc-BAT-P-DTBZ might be a potential imaging agent for monitoring VMAT2 binding sites in the pancreas.
The vesicular monoamine transporter type 2 (VMAT2) is a protein specifically located in the membrane of neurotransmitter storage vesicles of monoaminergic neurons (dopamine, serotonin, norepinephrine, and histamine) and was considered as a potential marker for noninvasive in vivo imaging of changes in monoaminergic innervation in human neurological diseases. Development efforts towards suitably radiolabeled compounds for in vivo imaging using positron emission tomography (PET) yielded optimized carbon-11 ((+)-α-[11C]dihydrotetrabenazine, DTBZ) and fluorine-18 (9-O-(3-[8F]fluoropropyl)dihydrotetrabenazine, AV-133) radioligands. Applications of VMAT2 radioligand imaging in animal models (mouse, rat, pig and nonhuman primate) and human studies of numerous neurodegenerative diseases (e.g., Parkinson’s and related movement disorders, dementia with Lewy bodies), psychiatric diseases (e.g., schizophrenia), and drug abuse (cocaine, methamphetamine) have demonstrated that in vivo imaging of the VMAT2 provides a powerful tool to investigate changes of monoaminergic innervation in human disease conditions.
New drugs introduced to the market every year represent privileged structures for particular biological targets. These new chemical entities (NCEs) provide insight into molecular recognition while serving as leads for designing future new drugs. This annual review describes the most likely process-scale synthetic approaches to thirty-one new chemical entities approved for the first time globally in 2017.
