- Formation and reactions of N7-aminoguanosine and derivatives
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Arylamines are mutagens and carcinogens and are thought to initiate tumors by forming adducts with DNA. The major adducts are C8-guanyl, and we have previously suggested a role for guanyl-N7 intermediates in the formation process. N7-Aminoguanosine (Guo) was synthesized and characterized, with the position of the NH2 at N7 established by two- dimensional rotating frame Overhauser enhancement NMR spectroscopy. In DMF, N7-NH2Guo formed C8-NH2Guo and the cyclic product C8:5'-O-cycloGuo. In aqueous media, these products were formed along with 8-oxo-7,8-dihydroGuo, N7-NH2guanine, and a product characterized as a purine 8,9-ring-opened derivative (N-aminoformamidopyrimidine). The rate of aqueous decomposition of N7-NH2Guo increased with pH, with a t( 1/2 ) of 10 h at pH 7 and a t( 1/2 ) of 2 h at pH 9. The rate of migration of NH2 from N7 to C8 is fast enough to explain the formation of C8-NH2Guo from the reaction of 2,4- dinitrophenoxyamine with Guo but not the formation of C8-(arylamino)Guo in the reaction of Guo with aryl hydroxylamine esters; however, the fluorenyl moiety may facilitate the proposed rearrangement by stabilizing an incipient negative charge in the transfer. In the reaction of Guo with N-hydroxy-2- aminofluorene and acetylsalicylic acid, a peak with the mass spectrum expected for N7-(2-aminofluorenyl)Guo was detected early in the reaction and was distinguished from C8-(2-aminofluorenyl)Guo. NMR experiments with [8- 13C]Guo also provided some additional support for transient formation of N7-(2-aminofluorenyl)Guo. We conclude that a guanyl-N7 intermediate is reasonable in the reaction of activated arylamines with nucleic acids, although an exact rate of transfer of an N7-arylamine group to the C8 position has not yet been quantified. The results provide an explanation for the numerous products associated with modification of DNA by activated arylamines. However, the contribution of 'direct' reaction at the guanine C8 atom cannot be excluded.
- Guengerich, F. Peter,Mundkowski, Ralf G.,Voehler, Markus,Kadlubar, Fred F.
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Read Online
- 2,2,2-Trifluoroacetaldehyde O-(Aryl)oxime: A Precursor of Trifluoroacetonitrile
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The preparation of 2,2,2-trifluoroacetaldehyde O-(aryl)oxime, a previously inaccessible precursor of trifluoroacetonitrile, via reaction of hydroxylamine and trifluoroacetaldehyde hydrate is reported. This precursor released CF3CN in quantitative yield under mildly basic conditions. The precursor was successfully used in the synthesis of trifluoromethylated oxadiazoles. The facile, cost-effective, scalable, and recyclable procedure makes these trifluoroacetonitrile precursors generally applicable.
- Lin, Bo,Yao, Yunfei,Huang, Yangjie,Weng, Zhiqiang
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p. 2055 - 2058
(2022/03/31)
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- Synthesis method of 2,4 -nitrobenzoic acid amine and reaction vessel
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The technical scheme is that the 2, 4 -dinitrobenzene oxyamine synthesis method comprises a box body, a reaction kettle arranged in the box body, a clamping assembly used for clamping the reaction kettle, and a moving assembly which drives the reaction kettle to move. A partition plate and vertically inserted into the box body covers the cover plate at the top end of the box body. The number of the separation plates is a plurality of partition plates, the box body is divided into a plurality of different chambers, and the cavity chambers are divided into discharge chambers arranged at the two ends and a heat preservation chamber arranged in the middle. The cover plate is arranged at the top end of the heat preservation chamber, and a heat preservation plate is arranged in the heat preservation chamber. This application has the effect of convenient regulation and control to the temperature of reaction.
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Paragraph 0025-0029
(2021/11/27)
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- Structure and Reactivity of a High-Spin, Nonheme Iron(III)-Superoxo Complex Supported by Phosphinimide Ligands
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Nonheme iron oxygenases utilize dioxygen to accomplish challenging chemical oxidations. A further understanding of the Fe-O2 intermediates implicated in these processes is challenged by their highly transient nature. To that end, we have developed a ligand platform featuring phosphinimide donors intended to stabilize oxidized, high-spin iron complexes. O2 exposure of single crystals of a three-coordinate Fe(II) complex of this framework allowed for in crystallo trapping of a terminally bound Fe-O2 complex suitable for XRD characterization. Spectroscopic and computational studies of this species support a high-spin Fe(III) center antiferromagnetically coupled to a superoxide ligand, similar to that proposed for numerous nonheme iron oxygenases. In addition to the apparent stability of this synthetic Fe-O2 complex, its ability to engage in a range of stoichiometric and catalytic oxidation processes demonstrates that this iron-phosphinimide system is primed for development in modeling oxidizing bioinorganic intermediates and green oxidation chemistry.
- Field, Mackenzie J.,Lee, Heui Beom,Rittle, Jonathan,Teat, Simon J.,Winslow, Charles
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supporting information
p. 13686 - 13693
(2021/09/11)
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- SUBSTITUTED TETRAHYDROISOQUINOLINE ETHYLBENZAMIDE ANTI-CANCER AGENTS
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The compounds herein disclosed are N-substituted tetrahydroisoquinoline ethylbenzamide compounds that have modifications on the phenyl rings by introducing groups with various electronic properties. These derivatives of N-substituted tetrahydroisoquinoline ethylbenzamide compounds have been shown to have anti-proliferative activity against cells. In particular, the compounds have been found to be effective in inhibiting the proliferation of cancer cells, such as cancer cells that originated in breast tissue. Additionally, it has been shown that the novel compounds have IC50 values against the breast cancer cells that are 6- to 10-fold less than the IC50 of Tamoxifen.
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- Enantioselective Synthesis of Chiral Oxime Ethers: Desymmetrization and Dynamic Kinetic Resolution of Substituted Cyclohexanones
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Axially chiral cyclohexylidene oxime ethers exhibit unique chirality because of the restricted rotation of C=N. The first catalytic enantioselective synthesis of novel axially chiral cyclohexylidene oximes has been developed by catalytic desymmetrization of 4-substituted cyclohexanones with O-arylhydroxylamines and is catalyzed by a chiral BINOL-derived strontium phosphate with excellent yields and good enantioselectivities. In addition, chiral BINOL-derived phosphoric acid catalyzed dynamic kinetic resolution of α-substituted cyclohexanones has been performed and yields versatile intermediates in high yields and enantioselectivities.
- Nimmagadda, Sri Krishna,Mallojjala, Sharath Chandra,Woztas, Lukasz,Wheeler, Steven E.,Antilla, Jon C.
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p. 2454 - 2458
(2017/02/23)
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- Visible Light as a Sole Requirement for Intramolecular C(sp3)-H Imination
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A novel, simple, and practical visible-light-mediated intramolecular α-C(sp3)-H imination of tertiary aliphatic amines containing β-O-aryl oximes leading to N-heterocycles has been developed. The reaction was performed well at rt with tolerance of some functional groups. Importantly, the selective C-H functionalization did not require added catalyst, oxidant, additive, acid, and base; visible light was the sole requirement.
- Li, Jingjing,Zhang, Pengxiang,Jiang, Min,Yang, Haijun,Zhao, Yufen,Fu, Hua
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p. 1994 - 1997
(2017/04/28)
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- Synthesis of 2,4-dinitrobenzene oxygen amine method
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The invention discloses a method for synthesizing 2,4-dinitrobenzene oxygen amine. The method comprises the following steps: adding hydroxylammonium salt, water and acetic ester into a reaction vessel according to the ratio of n (acetic ester): n (hydroxylammonium salt) being 1.0-2.0:1, dropwise adding 30% alkali metal hydroxide aqueous solution at 15-40 DEG C and continuously reacting for 1 hour according to the ratio of n (alkali metal hydroxide): n (hydroxylammonium salt) being 1.5-3; heating up to 50 DEG C after the reaction, dropwise adding an acetic ester solution of 2,4-dinitrochlorobenzene (at the concentration of 50%) according to the ratio of n (2,4-dinitrochlorobenzene): n (hydroxylammonium salt) being 0.5-1.0, and continuously reacting for 2 hours after dropwise adding; cooling, filtering, beating and washing with alkali lye; adding filter cake into the reaction vessel, adding equimolar hydrochloric acid, heating up and reacting for 1-3 hours, cooling and filtering; and recrystallizing the filter cake with methanol so as to obtain the product. According to the invention, reaction steps are short; raw materials are cheap and easily available; operation is simple; and the method is easy for industrial production.
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Paragraph 0034; 0035; 0036
(2016/12/22)
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- POLYCYCLIC COMPOUND INCLUDING PYRAZOLE AND ORGANIC LIGHT EMITTING DEVICE USING THE SAME
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The present invention refers to pyrazole containing an alkali-soluble polymer resin compound including multi annular ring relates to organic light emitting device.
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- PYRAZOLE-BASED COMPOUND AND ORGANIC LIGHT EMITTING DEVICE USING THE SAME
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The present invention relates to a pyrazole-based compound and an organic light emitting device comprising the same. The organic light emitting device comprises a positive electrode, a negative electrode, and one or more organic layers formed between the positive electrode and the negative electrode, wherein the organic layers comprise the pyrazole-based compound.COPYRIGHT KIPO 2015
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- PYRAZOLE-BASED COMPOUND AND ORGANIC LIGHT EMITTING DEVICE USING THE SAME
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The present invention relates to a pyrazole-based compound and an organic light emitting device comprising the same. The organic light emitting device comprises a positive electrode, a negative electrode, and one or more layers of organic layers formed between the positive electrode and the negative electrode, wherein one or more layers of organic layers comprise the pyrazole-based compound.COPYRIGHT KIPO 2015
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- Discovery of (S)-1-(1-(Imidazo[1,2- a ]pyridin-6-yl)ethyl)-6-(1-methyl-1 H -pyrazol-4-yl)-1 H -[1,2,3]triazolo[4,5- b ]pyrazine (Volitinib) as a Highly Potent and Selective Mesenchymal-Epithelial Transition Factor (c-Met) Inhibitor in Clinical Development for Treatment of Cancer
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HGF/c-Met signaling has been implicated in human cancers. Herein we describe the invention of a series of novel triazolopyrazine c-Met inhibitors. The structure-activity relationship of these compounds was investigated, leading to the identification of compound 28, which demonstrated favorable pharmacokinetic properties in mice and good antitumor activities in the human glioma xenograft model in athymic nude mice.
- Jia, Hong,Dai, Guangxiu,Weng, Jianyang,Zhang, Zhulin,Wang, Qing,Zhou, Feng,Jiao, Longxian,Cui, Yumin,Ren, Yongxin,Fan, Shiming,Zhou, Jinghong,Qing, Weiguo,Gu, Yi,Wang, Jian,Sai, Yang,Su, Weiguo
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supporting information
p. 7577 - 7589
(2014/12/11)
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- CERTAIN TRIAZOLOPYRIDINES AND TRIAZOLOPYRAZINES, COMPOSITIONS THEREOF AND METHODS OF USE THEREFOR
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Provided are certain triazolopyridines and triazolopyrazines, compositions thereof and methods of use therefor.
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- COMPOUNDS AND COMPOSITIONS AS TRK INHIBITORS
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The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated TRK kinase activity.
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- Elusive metal-free primary amination of arylboronic acids: Synthetic studies and mechanism by density functional theory
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Herein, we disclose the first metal-free synthesis of primary aromatic amines from arylboronic acids, a reaction that has eluded synthetic chemists for decades. This remarkable transformation affords structurally diverse primary arylamines in good chemical yields, including a variety of halogenated primary anilines that often cannot be prepared via transition-metal-catalyzed amination. The reaction is operationally simple, requires only a slight excess of aminating agent, proceeds under neutral or basic conditions, and, importantly, can be scaled up to provide multigram quantities of primary anilines. Density functional calculations reveal that the most likely mechanism involves a facile 1,2-aryl migration and that the presence of an ortho nitro group in the aminating agent plays a critical role in lowering the free energy barrier of the 1,2-aryl migration step.
- Zhu, Chen,Li, Gongqiang,Ess, Daniel H.,Falck, John R.,Kürti, László
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supporting information
p. 18253 - 18256
(2013/01/15)
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- CERTAIN TRIAZOLOPYRIDINES AND TRIAZOLOPYRAZINES, COMPOSITIONS THEREOF AND METHODS OF USE THEREFOR
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Provided are certain triazolopyridines and triazolopyrazines, compositions thereof and methods of use therefor.
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- NOVEL COMPOUNDS HAVING INDAZOLE FRAMEWORKS, METHODS FOR PREPARING THE SAME AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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Novel compounds having indazole frameworks, as well as a method for preparing the same and a pharmaceutical composition comprising the same are provided. The compounds of the present invention can inhibit protein kinase activity and thus the pharmaceutical composition of the present invention can be used to prevent or treat diseases or disorders which are related to protein kinase activity.
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Page/Page column 9
(2010/10/19)
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- IMIDAZOPYRIDINE AND RELATED ANALOGS AS SIRTUIN MODULATORS
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Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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- NOVEL COMPOUNDS HAVING INDAZOLE FRAMEWORKS, METHODS FOR PREPARING THE SAME AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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Novel compounds having indazole frameworks, as well as a method for preparing the same and a pharmaceutical composition comprising the same are provided. The compounds of the present invention can inhibit protein kinase activity and thus the pharmaceutical composition of the present invention can be used to prevent or treat diseases or disorders which are related to protein kinase activity.
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Page/Page column 11
(2009/04/25)
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- Fischer synthesis of isomeric thienopyrrole LHRH antagonists
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As part of a structure-activity exploration into LHRH antagonists, structures containing the thieno[2,3-b]pyrrole core were identified as potent antagonists. This letter describes the employment of the Fischer synthesis to access this thienopyrrole and isomeric final compounds.
- Andrews, David M.,Arnould, Jean-Claude,Boutron, Pascal,Délouvrie, Bénédicte,Delvare, Christian,Foote, Kevin M.,Hamon, Annie,Harris, Craig S.,Lambert-van der Brempt, Christine,Lamorlette, Maryannick,Matusiak, Zbegniew M.
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experimental part
p. 5805 - 5816
(2009/12/24)
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- Highly efficient synthesis of o-(2,4-dinitrophenyl)hydroxylamine. Application to the synthesis of substituted N-benzoyliminopyridinium ylides
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An efficient two-step synthesis of O-(2,4-dinitrophenyl)hydroxylamine is described along with a comparison of its aminating efficiency with O-mesitylenesulfonylhydroxylamine (MSH). It was used in an expedient N-amination/benzoylation procedure involving various substituted pyridines, leading to polysubstituted N-benzoyliminopyridinium ylides, and the scope of its amination power was studied.
- Legault, Claude,Charette, Andre B.
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p. 7119 - 7122
(2007/10/03)
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- 1-amino-3-(bicyclic heterocyclyl)-6-fluoroalkyluracils
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Herbicidal 1-Amino-3-(bicyclic heterocyclyl)-6-fluoroalkyluracils of the formula STR1 in which M is fluoroalkyl(C1-6); R1 is hydrogen or alkyl(C1-6); R2 is hydrogen or alkyl (C1-6); Y is hydrogen, fluorine, chlorine, or bromine; X is hydrogen, fluorine, chlorine, bromine, cyano, alkyl(C1-6), or fluoroalkyl(C1-6); and n is 0 or 1.
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- Preparation of N-nitrohydroxyamines by diresct nitration
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The possibilities for stabilization of compounds with the A-B-NO2 fragment, where A is an atom containing a lone electron pair, were examined.It was shown that N-methyl-O-2,4-dinitro- and 2,4,6-trinitrophenylhydroxyamines undergo nitration with nitronium tetrafluoroborate or with a mixture of nitric acid and acetic anhydride to give the corresponding N-nitrohydroxylamines in high yields.N-Nitro-2,4-dinitrohydroxylamine that contains no methyl group at the nitrogen atom is unstable and forms a product of O-alkylation upon reaction with diazomethane. - Key words: N-nitrohydroxylamines; nitration.
- Khodot, E. N.,Petrova, I. M.,Anikin, O. V.,Chlenov, I. E.
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p. 2183 - 2185
(2007/10/03)
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- Stereo- and Regioselective Total Synthesis of the Hydropyridoquinolizine Ladybug Defensive Alkaloids
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The stereo- and regioselective syntheses of the ladybug defensive alkaloids coccinelline (1), precoccinelline (2), (+/-)-hippodamine (3), (+/-)-convergine (4), (+/-)-hippocasine (5), (+/-)-hippocasine oxide (6), myrrhine (7), (+/-)-propyleine (8), and (+/-)-isopropyleine (9) are described starting from perhydroboraphenalene.
- Mueller, Richard H.,Thompson, Mark E.,DiPardo, Robert M.
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p. 2217 - 2231
(2007/10/02)
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