- In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain
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Monoamine oxidases (MAOs) play a key role in the metabolism of major monoamine neurotransmitters. In particular, the upregulation of MAO-B in Parkinson's disease, Alzheimer's disease and cancer augmented the development of selective MAO-B inhibitors for d
- Duki?-Stefanovi?, Sladjana,Hang Lai, Thu,Toussaint, Magali,Clau?, Oliver,Jevti?, Ivana I.,Penji?evi?, Jelena Z.,Andri?, Deana,Ludwig, Friedrich-Alexander,Gündel, Daniel,Deuther-Conrad, Winnie,Kosti?-Raja?i?, Sladjana V.,Brust, Peter,Teodoro, Rodrigo
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- Targeting cyclic nucleotide phosphodiesterase 5 (PDE5) in brain: Toward the development of a PET radioligand labeled with fluorine-18
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With the aim to develop a specific radioligand for imaging the cyclic nucleotide phosphodiesterase 5 (PDE5) in brain by positron emission tomography (PET), seven new fluorinated inhibitors (3–9) were synthesized on the basis of a quinoline core. The inhibitory activity for PDE5 together with a panel of other PDEs was determined in vitro and two derivatives were selected for IC50 value determination. The most promising compound 7 (IC50 = 5.92 nM for PDE5A), containing a 3-fluoroazetidine moiety, was further radiolabeled by aliphatic nucleophilic substitution of two different leaving groups (nosylate and tosylate) using [18F]fluoride. The use of the nosylate precursor and tetra-n-butyl ammonium [18F]fluoride ([18F]TBAF) in 3-methyl-3-pentanol combined with the addition of a small amount of water proved to be the best radiolabeling conditions achieving a RCY of 4.9 ± 1.5% in an automated procedure. Preliminary biological investigations in vitro and in vivo were performed to characterize this new PDE5 radioligand. Metabolism studies of [18F]7 in mice revealed a fast metabolic degradation with the formation of radiometabolites which have been detected in the brain.
- Wenzel, Barbara,Liu, Jianrong,Dukic-Stefanovic, Sladjana,Deuther-Conrad, Winnie,Teodoro, Rodrigo,Ludwig, Friedrich-Alexander,Chezal, Jean-Michel,Moreau, Emmanuel,Brust, Peter,Maisonial-Besset, Aurelie
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- A Water-Soluble Copper-Polypyridine Complex as a Homogeneous Catalyst for both Photo-Induced and Electrocatalytic O2 Evolution
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The water-soluble polypyridine copper complex [Cu(F3TPA)(ClO4)2] [1; F3TPA=tris(2-fluoro-6-pyridylmethyl)amine] catalyzes water oxidation in a pH 8.5 borate buffer at a relatively low overpotential of 610 mV. Assisted by photosensitizer and an electron acceptor, 1 also exhibits activity as a homogeneous catalyst for photo-induced O2 evolution with a maximum turnover frequency (TOF) of (1.58±0.03)×10-1 s-1 and a maximum turnover number (TON) of 11.61±0.23. In comparison, the reference [Cu(TPA)(ClO4)2] [TPA=tris(2-pyridylmethyl)amine] displayed almost no activity under either set of conditions, implying the crucial role of the ligand in determining the behavior of the catalyst. Experimental evidence indicate the molecular catalytic nature of 1, leading to a potentially practical strategy to apply the copper complex in a photoelectrochemical device for water oxidation.
- Xiang, Rui-Juan,Wang, Hong-Yan,Xin, Zhi-Juan,Li, Cheng-Bo,Lu, Ya-Xing,Gao, Xue-Wang,Sun, Hua-Ming,Cao, Rui
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- Cap-dependent protease inhibitor
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The invention relates to a compound with cap-dependent endonuclease inhibitory activity and application of the compound in the aspect of influenza treatment.
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Paragraph 0059-0062
(2021/06/09)
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- Hetero-aromatic compound and its use in medicine (by machine translation)
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The invention discloses heteroaromatic compound and its use in medicine, in particular, the invention provides a hetero-aromatic compound or its stereoisomers, geometric isomers, tautomers, racemate, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug, and containing said pharmaceutical composition; the invention also discloses the compound or its pharmaceutical compositions in use for preparing a medicament, and in the treatment of autoimmune diseases or proliferative diseases of application. (by machine translation)
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Paragraph 0729; 0730
(2017/08/29)
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- TETRAHYDROCYCLOPENTA[b] INDOLE COMPOUNDS AS ANDROGEN RECEPTOR MODULATORS
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The present invention provides a compound of the formula: Formula (I) or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising a compound of Formula (I) in combination with a suitable carrier, diluent, or excipient; and methods for treating physiological disorders, particularly reduced bones mass, osteoporosis, osteopenia, or reduced muscle mass or strength, comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt thereof. X-17142.
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Page/Page column 14
(2010/04/23)
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- Chelation-assisted, copper(II)-acetate-accelerated azide-alkyne cycloaddition
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We described in a previous communication a variant of the popular Cu I-catalyzed azide-alkyne cycloaddition (AAC) process where 5 mol % of Cu(OAc)2 in the absence of any added reducing agent is sufficient to enable the reaction. 2-Picolylazide (1) and 2-azidomethylquinoline (2) were found to be by far the most reactive carbon azide substrates that convert to 1,2,3-triazoles in as short as a few minutes under the discovered conditions. We hypothesized that the abilities of 1 and 2 to chelate CuII contribute significantly to the observed high reaction rates. The current work examines the effect of auxiliary ligands near the azido group other than pyridyl for CuII on the efficiency of the Cu(OAc)2-accelerated AAC reaction. The carbon azides capable of binding to the catalytic copper center at the alkylated azido nitrogen in a chelatable fashion were indeed shown to be superior substrates under the reported conditions. The chelation between carbon azide 11 and CuII was demonstrated in an X-ray single-crystal structure. In a limited set of examples, the ligand tris(benzyltriazolylmethyl) amine (TBTA), developed by Fokin et al. for assisting the original Cu I-catalyzed AAC reactions, also dramatically enhances the Cu(OAc)2-accelerated AAC reactions involving nonchelating azides. This observation leads to the hypothesis of an additional effect of chelating azides on the efficiencies of Cu(OAc)2-accelerated AAC reactions, which is to facilitate the rapid reduction of CuII to highly catalytic CuI species. Mechanistic studies on the AAC reactions with particular emphasis on the role of carbon azide/copper interactions will be conducted based on the observations reported in this work. Finally, the immediate utility of the product 1,2,3-triazole molecules derived from chelating azides as multidentate metal coordination ligands is demonstrated. The resulting triazolyl-containing ligands are expected to bind with transition metal ions via the N(2) nitrogen of the 1,2,3-triazolyl group to form nonplanar coordination rings. The CuII complexes of bidentate T1 and tetradentate T6 and the ZnII complex of T6 were characterized by X-ray crystallography. The structure of [Cu(T1)2(H2O) 2](ClO4)2 reveals the interesting synergistic effect of hydrogen bonding, π-π stacking interactions, and metal coordination in forming a one-dimensional supramolecular construct in the solid state. The tetradentate coordination mode of T6 may be incorporated into designs of new molecule sensors and organometallic catalysts.
- Kuang, Gui-Chao,Michaels, Heather A.,Simmons, J. Tyler,Clark, Ronald J.,Zhu, Lei
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supporting information; experimental part
p. 6540 - 6548
(2010/12/19)
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- TETRAHYDROCARBAZOLE DERIVATIVES USEFUL AS ANDROGEN RECEPTOR MODULATORS
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The present invention provides a compound of the formula: Formula I or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising an effective amount of a compound of Formula I in combination with a suitable carrier, diluent, or ex
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Page/Page column 148-149
(2010/11/25)
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