- Synthesis and characterization of 8-aminoquinolines, substituted by electron donating groups, as high-affinity copper chelators for the treatment of Alzheimer's disease
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The deregulation of copper homeostasis generates copper–amyloid aggregation and strongly participates in neuron damage in the brains of patients with Alzheimer's disease. Therefore, copper chelators able to regulate copper homeostasis should be considered
- Huang, Ju,Nguyen, Michel,Liu, Yan,Robert, Anne,Meunier, Bernard
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Read Online
- Synthesis and Evaluation of Fluorine-18 Labeled 2-Phenylquinoxaline Derivatives as Potential Tau Imaging Agents
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In this study, three pairs of optically pure 18F-labeled 2-phenylquinoxaline derivatives were evaluated as Tau imaging agents for the diagnosis of Alzheimer's disease (AD). The chiral 2-fluoromethyl-1,2-ethylenediol side chain was attached to the 2-phenyl
- Zhou, Kaixiang,Yang, Fan,Li, Yuying,Chen, Yimin,Zhang, Xiaojun,Zhang, Jinming,Wang, Junfeng,Dai, Jiapei,Cai, Lisheng,Cui, Mengchao
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p. 1176 - 1195
(2021/02/06)
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- Pyrazole spleen tyrosine kinase inhibitor as well as preparation method and application thereof
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The invention discloses a pyrazole spleen tyrosine kinase inhibitor, a preparation method thereof, a pharmaceutical composition containing the same, and application of the pyrazole spleen tyrosine kinase inhibitor and the pharmaceutical composition in the preparation of drugs for treating Syk-mediated diseases including cancers, inflammatory diseases and the like.
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Paragraph 0256-0263
(2020/12/29)
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- 2 -aryl quinoxaline compound with affinity with Tau protein as well as preparation method and application thereof (by machine translation)
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The invention provides 2 -arylquinoxaline compounds with affinity with Tau protein, and the structure is as shown in a formula (I). The invention further provides a preparation method of the compound of the formula (I). The compound can be directly used a
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Paragraph 0034; 0083; 0084
(2020/12/30)
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- Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization
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PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments, with a Kd of 0.987 μM. Kinetic experiments indicated that 17 was a SAM competitive inhibitor other than the substrate. In addition, 17 showed selective antiproliferative effects against MV4-11 cells, and further studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation. 17 may represent a promising lead compound to understand more about PRMT5 and potentially assist the development of treatments for leukemia indications.
- Mao, Ruifeng,Shao, Jingwei,Zhu, Kongkai,Zhang, Yuanyuan,Ding, Hong,Zhang, Chenhua,Shi, Zhe,Jiang, Hualiang,Sun, Dequn,Duan, Wenhu,Luo, Cheng
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p. 6289 - 6304
(2017/08/02)
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- Interaction of bisbenzimidazole-substituted carbazole derivatives with G-quadruplexes and living cells
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G-quadruplex (G4) ligands have potential as chemotherapeutic agents because of the important roles of G4s in regulation of genomic function. Previously, we have developed a fluorescent probe (termed as BPBC) with excellent selectivity to parallel G4s, which possesses a V-shaped bisbenzimidazole-substituted carbazole planar core and two methylpiperazine side arms. Here, we further investigated the interactions of BPBC derivatives with different DNA and living cells. The spectral analysis showed that non-substituted bisbenzimidazole-substituted carbazole (7c) and bisdimethylamino-substituted 7c (7b) exhibited good selectivity to parallel G4s. The binding affinities of BPBC derivatives to parallel G4s were BPBC > 7b 7c. BPBC and 7b entered living cells and mainly located in the cytoplasma and nucleoli; 7c mainly located in the lysosome. BPBC exhibited the highest cytotoxicity with IC50 around 1 μM. Our results suggest that the bisbenzimidazole-substituted carbazole core is the key factor for selectively binding BPBC derivatives to parallel G4s; the side arms can change their affinity to specific G4s, as well as their interaction with cells. Further optimization of the side arms will provide the opportunity to obtain chemotherapeutic agents targeting specific G4s in cells.
- Wei, Yongbiao,Zhang, Xin,Wang, Linlin,Liu, Ying,Bing, Tao,Liu, Xiangjun,Shangguan, Dihua
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p. 75911 - 75917
(2015/09/28)
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- RADIOPROTECTOR COMPOUNDS AND METHODS
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The invention relates to novel compounds, processes for their preparation and their use in protecting biological materials from radiation damage (radioprotection). Preferred compounds of the invention are those of Formula (II), as follows: wherein W represents -N(R1R2) where R1 and R2 are not both hydrogen and where they may together form a 5, 6 or 7 membered ring structure, -NHN(R1R2), NHR3N(R1R2), -NHR3OR2, -N(R3)R3OR2, -N(R1)R3OR3OR3, OR3NR1R2, -OR3 or W represents piperidyl, piperazinyl, morpholinyl, thiomorpholinyl or diazepanyl each of which may be optionally substituted by C1 to C4 alkyl, C2 to C4 alkenyl, -N(CO)N(R1R2), -N(CO)OR1, -N(CO)OR3OH, -(CO)NR1R2, -R3(CO)NR1R2, -R3OR1, -OR1, -N(R1R2) OR -NH-; R1 and R2 are the or different and are selected from hydrogen, C1 to C4 alkyl or C2 to C4 alkenyl; group or chain; Z is the same or different and represents N or CH; Z' is the same or different and represents N or C; X represents CH, N or NH, where .. is a double bond when X is CH or N and a single bond when X is NH; X' represents N or NH, wherein when X is CH or N X' is NH and wherein X and X' are different and further where ~~~is a double bond when X' is N and a single bond when X' is NH; Q represents H, alkoxyl, -NR1R2, F or Cl; Q1 is absent when Z' is N and when Z' is C it represents H, alkoxyl, -NR1R2, F or Cl; A represents a five to ten membered single or multiple ring structure with heterocyclic N or O located at the ortho position, said ring including optional double bonds, substitutions and/or other heteroatoms and pharmaceutically acceptable derivatives thereof.
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Page/Page column 99
(2011/10/31)
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- MEDIATORS OF HEDGEHOG SIGNALING PATHWAYS, COMPOSITIONS AND USES RELATED THERETO
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The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting the cell with a hedgehog antagonist of formula (I) in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity.
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Page/Page column 111
(2008/06/13)
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- Sensing metal ions with DNA building blocks: Fluorescent pyridobenzimidazole nucleosides
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We describe novel fluorescent N-deoxyribosides (1 and 2) having 2-pyrido-2-benzimidazole and 2-quino-2-benzimidazole as aglycones. The compounds were prepared from the previously unknown heterocyclic precursors and Hoffer's chlorosugar, yielding alpha ano
- Kim, Su Jeong,Kool, Eric T.
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p. 6164 - 6171
(2007/10/03)
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- DYES
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A colorant for coloring keratin fibers wherein the colorant contains a substantive dye which is a 4-nitroaniline derivative corresponding to formula (I): 1in which R1, R2, R3 and R4 independently of one another represent a hydrogen atom, an alkyl, hydroxyalkyl, alkoxyalkyl, carbamyl alkyl, mesylaminoalkyl, acetylaminoalkyl, ureidoalkyl, carbalkoxyaminoalkyl, sulfalkyl, piperidinoalkyl, morpholinoalkyl or phenyl radical optionally substituted by an amino group in the para position, the alkyl or alkoxy groups containing 1 to 4 carbon atoms, with the proviso that the four substituents R1, R2, R3 and R4 do not simultaneously represent hydrogen, and the groups —NR1R2 and —NR3R4 may also represent an aziridine, acetidine, pyrrolidine, piperidine, azepan, azocine, morpholine, thiomorpholine or piperazine ring which may also bear another substituent R8 at the nitrogen atom, R8 being a hydrogen atom, a (C1-4)-alkyl, hydroxy-(C2-3)-alkyl, (C1-4)-alkoxy-(C2-3)-alkyl, amino-(C2-3)-alkyl or 2,3-dihydroxypropyl group, and R5, R6 and R7 independently of one another represent ahydrogen atom, a halogen atom, a (C1-4)-alkyl, (C1-4)-alkoxy, carboxy, sulfo or (C2-4)-hydroxyalkyl group, or a physiologically compatible salt of the compounds with an inorganic or organic acid.
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- [125I/127I]iodoHoechst 33342: synthesis, DNA binding, and biodistribution.
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An iodinated analog of the DNA-minor-groove-binding agent Hoechst 33342 has been synthesized and evaluated for DNA binding and tumor targeting. The bis-benzimidazole ring system of the title compound was constructed from the piperazinyl terminus via a Pinner-type cyclization followed by oxidative cyclization of the diamine Schiff base. To synthesize radioiodoHoechst 33342, (trimethylstannyl)Hoechst 33342 was prepared by the same strategy and subjected to mild radioiododestannylation in the presence of lactoperoxidase. After purification by HPLC, the radiochemical was separated in carrier-free form with > 85% radiochemical yield and > 99% chemical and radiochemical purity. Fluorescence spectrometric analysis of the binding of iodoHoechst 33342 to calf thymus DNA gave an equilibrium association constant (Ka) of 2.57 x 10(7) M-1 comparable to the Ka value of Hoechst 33342. Fluorescence microscopy of viable V79 cells demonstrated that the iodinated dye stained the nuclei with avidity similar to that of the noniodinated dye. The biodistribution of [125I]-iodoHoechst 33342 in LS174T tumor-bearing athymic mice 4 h postadministration showed a tumor uptake of 3-4% injected dose per gram (ID/g), tumor/blood ratio of 6-8, and tumor/ nontumor ratios above unity for most organs. A low thyroid uptake (approximately 2% ID/g) indicated that the radiochemical did not deiodinate and was stable in vivo.
- Harapanhalli,McLaughlin,Howell,Rao,Adelstein,Kassis
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p. 4804 - 4809
(2007/10/03)
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In connection with our work on styryl derivatives of benzodiazinones, we have prepared the 7-N, N-dimethylamino-3-methyl-l , 4-benzodiazin-2-one 4a and two chromo-and fluoroionophores derived from the monoaza-15-crown-5 and styrylbenzodiazinones. A structural study of these compounds by 1H and l3C NMR, UV spectrophotometry, and molecular modelling was carried out. Unlike styrylbenzoxazinones, styrylbenzodiazinone derivatives showed a Z/E isomerization in acetonitrile solution. The isomerization was photoinduced, was catalysed by metallic ions, and was a reversible process. As well, an efficient alkylation reaction of the lactam function of benzodiazinones is described.
- Cazaux, Louis,Faher, Mourad,Picard, Claude,Tisnes, Pierre
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p. 1236 - 1246
(2007/10/02)
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- DERIVATIVES OF 5(6)-AMINOBENZIMIDAZOLE
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A series of triamines were obtained by the amination of 2-nitro-5-chloroaminobenzene and reduction of the obtained compounds.In reaction with the esters of aromatic acids the products were converted into derivatives of 5(6)-aminobenzimidazole.
- Kuznetsov, V. A.,Garabadzhiu, A. V.,Ginzburg, O. F.
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p. 576 - 580
(2007/10/02)
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