- Design, synthesis, and biological evaluation of quinazoline derivatives as dual HDAC1 and HDAC6 inhibitors for the treatment of cancer
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Fifty-eight quinazoline-based compounds were designed and synthesized based on the structural optimizations from the lead compound 23bb in an attempt to search for more potent dual HDAC1 and HDAC6 inhibitors. Among them, 32c (HDAC1, IC50?=?31.1
- Chen, Jinying,Sang, Zitai,Jiang, Youjun,Yang, Chao,He, Linhong
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p. 232 - 241
(2018/11/02)
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- Preparation method for osimertinib mesylate
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The invention discloses a preparation method for osimertinib mesylate. The chemical name of osimertinib mesylate is N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidine-2-yl)amino)phenyl)acrylamide mesylate (AZD9291), and the chemical formula is C28H33N7O2.CH4O3S. The process of the preparation technique of the preparation method is simple, materials areeasy to obtain, and the preparation method is cost-efficient and environment-friendly, can help realize industrialization, can promote the economic and technological development of osimertinib activeingredients, reduces production cost, and is suitable for mass production.
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Paragraph 0013; 0014
(2018/04/28)
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- 2 - Amino - 4 - acetamido anisole novel synthesis process (by machine translation)
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The present invention provides a novel 2 - amino - 4 - acetamido anisole synthesis process, the usage of palladium bi-metal catalysts and the palladium/carbon catalyst to replace Rany - Ni catalyst, to the anisole on the nitro-selective catalytic hydrogenation, which not only reduces use Rany - Ni catalyst of post-industrial risks, while at the same time, the resulting 2 - amino - 4 - acetyl anisole purity higher, greater yield. (by machine translation)
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Paragraph 0059-0060; 0072; 0081
(2018/03/01)
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- 2,4-dibasic miazines compound
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The invention belongs to the field of medical chemistry, relates to a 2,4-dibasic miazines compound and specifically relates to a compound shown as formula (I) or a pharmaceutically acceptable salt thereof, a drug compound thereof and an application thereof in treating EGFR or/and ALK mediated diseases.
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- Method for synthesizing 3-amino-4-methoxy acetanilide by binary alloy catalysis
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The invention relates to a method for synthesizing 3-amino-4-methoxy acetanilide by catalytically hydrogenising 3-nitro-4-methoxy acetanilide (NMA) with a nano copper/ silver binary alloy catalyst, and belongs to the field of nano catalysis. The reaction
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Paragraph 0027; 0028; 0029; 0030; 0031; 0032; 0033-0054
(2017/04/29)
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- 2-amino-4 - (β-hydroxyethyl amino) anisole and its sulphate preparation method
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The invention relates to 2-amino-4-(beta-hydroxyethylamino) methoxybenzene and a preparation method of 2-amino-4-(beta-hydroxyethylamino) methoxybenzene sulfate. The preparation method comprises the steps as follows: 3-nitro-para-fluoroaniline is adopted as a raw material and subjected to nucleophilic substitution to produce 3-nitro-4-anisidine; 3-nitro-4-anisidine and chloroethyl chloroformate are subjected to condensation to synthesize 2-nitro-4-(beta-hydroxyethylamino) methoxybenzene with a hydrolysis and decarboxylation one-pot method; and 2-nitro-4-(beta-hydroxyethylamino) methoxybenzene has the hydrogenation reduction reaction to obtain a target product 2-amino-4-(beta-hydroxyethylamino) methoxybenzene which reacts with sulfate salt to obtain 2-amino-4-(beta-hydroxyethylamino) methoxybenzene sulfate. 2-amino-4-(beta-hydroxyethylamino) methoxybenzene and the preparation method of 2-amino-4-(beta-hydroxyethylamino) methoxybenzene sulfate have the advantages of high product quality, good yield, stable technology, small emission of three wastes, low cost, good economic efficiency and the like, and synthesis materials are easy to obtain.
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Paragraph 0055; 0057
(2017/04/06)
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- Altering the regioselectivity of a nitroreductase in the synthesis of arylhydroxylamines by structure-based engineering
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Nitroreductases have great potential for the highly efficient reduction of aryl nitro compounds to arylhydroxylamines. However, regioselective reduction of the desired nitro group in polynitroarenes is still a challenge. Here, we describe the structure-based engineering of Escherichia coli nitroreductase NfsB to alter its regioselectivity, in order to achieve reduction of a target nitro group. When 2,4-dinitrotoluene was used as the substrate, the wild-type enzyme regioselectively reduced the 4-NO2 group, but the T41L/N71S/F124W mutant primarily reduced the 2-NO2 group, without loss of activity. The crystal structure of T41L/N71S/F124W and docking experiments indicated that the regioselectivity change (from 4-NO2 to 2-NO2) might result from the increased hydrophobicity of residues 41 and 124 (proximal to FMN) and conformational changes in residues 70 and 124. The regioselectivity of nitroreductase NfsB from E. coli toward 2,4-dinitrotoluene was shifted from the 4-NO2 group to the 2-NO2 group without loss of activity, by introducing three mutations: T41L, N71S, and F124W. This study provides an example of a tailored enzyme for regioselective synthesis of the target arylhydroxylamines.
- Bai, Jing,Zhou, Yong,Chen, Qi,Yang, Qing,Yang, Jun
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p. 1219 - 1225
(2015/05/27)
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- Design, synthesis, and biological evaluation of (E)-N-Aryl-2- arylethenesulfonamide analogues as potent and orally bioavailable microtubule-targeted anticancer agents
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A series of novel (E)-N-aryl-2-arylethenesulfonamides (6) were synthesized and evaluated for their anticancer activity. Some of the compounds in this series showed potent cytotoxicity against a wide spectrum of cancer cell-lines (IC50 values ranging from 5 to 10 nM) including all drug resistant cell-lines. Nude mice xenograft assays with compound (E)-N-(3-amino-4- methoxyphenyl)-2-(2′,4′,6′-trimethoxyphenyl)ethenesulfonamide (6t) showed dramatic reduction in tumor size, indicating their in vivo potential as anticancer agents. A preliminary drug development study with compound 6t is predicted to have increased blood-brain barrier permeability relative to many clinically used antimitotic agents. Mechanistic studies indicate that 6t and some other analogues disrupted microtubule formation, formation of mitotic spindles, and arrest of cells in mitotic phase. Compound 6t inhibited purified tubulin polymerization in vitro and in vivo and circumvented drug resistance mediated by P-glycoprotein. Compound 6t specifically competed with colchicine binding to tubulin and with similar avidity as podophylltoxin, indicating its binding site on tubulin.
- Reddy, M. V. Ramana,Mallireddigari, Muralidhar R.,Pallela, Venkat R.,Cosenza, Stephen C.,Billa, Vinay K.,Akula, Balaiah,Subbaiah, D. R. C. Venkata,Bharathi, E. Vijaya,Padgaonkar, Amol,Lv, Hua,Gallo, James M.,Reddy, E. Premkumar
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p. 5562 - 5586
(2013/07/26)
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- Functionalized alkoxy arene diazonium salts from paracetamol
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Arene diazonium tetrafluoroborates can be synthesized from aromatic acetamides via a sequence of deacetylation, diazotation and precipitation, induced by anion exchange. The reaction is conducted as a convenient one-flask transformation with consecutive addition of the appropriate reagents. Exchange of solvents or removal of byproducts prior to isolation of the product is not required. The arene diazonium salts are isolated from the reaction mixture by simple filtration. Two complementary protocols are presented, and the utility of the reaction is exemplified for a synthesis of the diarylheptanoid natural product de-O-methyl centrolobine.
- Schmidt, Bernd,Berger, Rene,Hoelter, Frank
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supporting information; experimental part
p. 1406 - 1414
(2010/06/19)
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- Efficient and practical cross-coupling of arenediazonium tetrafluoroborate salts with boronic acids catalyzed by palladium(0)/barium carbonate
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The cross-coupling reaction of arenediazonium tetrafluoroborate salts with boronic acids catalyzed by the unusual palladium(0)/barium carbonate catalyst is described as an extremely practical and highly efficient alternative to classical homogeneous conditions. Reactions are conducted under mild conditions at room temperature without any base and ligand. The opportunity of preparing unsymmetrical terphenyls in a one-pot process is also demonstrated. Finally, the power of this methodology is highlighted by the synthesis of Bifenazate.
- Felpin, Francois-Xavier,Fouquet, Eric
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supporting information; experimental part
p. 863 - 868
(2009/05/07)
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- Mono-nitration of aromatic compounds via their nitric acid salts
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Aromatic compounds bearing a basic nitrogen atom can be converted to the corresponding nitric acid salts. Mono-nitration of the compounds can be carried out by adding a dichloromethane solution of the salts to sulfuric acid, or by adding acetyl chloride (or trifluoroacetic anhydride) to a dichloromethane solution of the salts. This protocol provides, among other benefits, the most convenient and reliable way for the prevention of over-/under-nitration and is especially suitable for scale-up.
- Zhang, Pingsheng,Cedilote, Miall,Cleary, Thomas P.,Pierce, Michael E.
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p. 8659 - 8664
(2008/03/30)
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- Mono-nitration of aromatic compounds via nitrate salts
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A method of nitrating a compound selected from the group consisting of is provided.
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Page/Page column 11
(2008/06/13)
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- Effect of the electronic structure of the radical anions of 4-substituted 1,2-and 1,3-dinitrobenzenes on the regioselectivity of reduction of the nitro groups
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Theoretical and experimental regularities of the regioselectivity of the reduction of one of the two nitro groups in unsymmetrical dinitrobenzenes were studied. It was found that the regioselectivity of the formation of isomeric nitroanilines depends on the structure of the substrate and the nature of the reducing agent. The reduction regioselectivity model was verified, according to which radical anion protonation is the major reaction direction. Pleiades Publishing, Inc. 2006.
- Orlov,Begunov,Demidova,Rusakov
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- Guanidinium nitrate: A novel reagent for aryl nitrations
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Nitration of various aromatic compounds utilising guanidinium nitrate in 85% sulfuric acid as a nitrating agent has been studied.
- Ramana,Malik,Parihar
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p. 8681 - 8683
(2007/10/03)
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- Synthesis, biodistribution and micro-PET imaging of radiolabeled antimitotic agent T138067 analogues
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Radiolabeled antimitotic agents [11C]T138067 and [ 18F]T138067 have been synthesized for evaluation as new potential positron emission tomography (PET) biomarkers for cancer imaging. In vivo biodistribution and micro-PET imaging of [
- Fei, Xiangshu,Zheng, Qi-Huang,Wang, Ji-Quan,Stone, K. Lee,Martinez, Tanya D.,Miller, Kathy D.,Sledge, George W.,Hutchins, Gary D.
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p. 1247 - 1251
(2007/10/03)
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- 3-cyanoquinolines, 3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors
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This invention provides compounds of Formula (I), having the structure where T, Z, X, A, R1, R2a, R2b, R2c, R3, R4, and n are defined herein, or a pharmaceutically acceptable salt thereof which are useful as antineoplastic agents and in the treatment of osteoporosis and polycystic kidney disease.
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- Arylsulfonanilide ureas
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The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states,
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- Hydrophilic, pro-drug analogues of T138067 are efficacious in controlling tumor growth in vivo and show a decreased ability to cross the blood brain barrier
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The novel anticancer compound T138067 is an irreversible inhibitor of tubulin polymerization. Amides 3-6 were synthesized using standard methodologies and determined to be significantly less lipophilic than T138067 based on logP calculations. Tubulin poly
- Rubenstein,Baichwal,Beckmann,Clark,Frankmoelle,Roche,Santha,Schwender,Thoolen,Ye,Jaen
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p. 3599 - 3605
(2007/10/03)
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- Arylsulfonanilide derivatives
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The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states,
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- Concerning the baker's yeast (Saccharomyces cerevisiae) mediated reduction of nitroarenes and other N-O containing functional groups
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Nitro- and nitrosoarenes can be reduced using baker's yeast (Saccharomyces cerevisiae) under two distinct sets of conditions, one of which is in fact a well established non-enzymic process. In order to clarify reports in the literature a comparison of the two methods has been made.
- Blackie, Josie A.,Turner, Nicholas J.,Wells, Andrew S.
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p. 3043 - 3046
(2007/10/03)
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- Regioselective Reduction of Substituted Dinitroarenes Using Baker's Yeast
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A range of substituted dinitroaromatic compounds have been reduced using baker's yeast (Saccharamyces cerevisiae), in some cases with very high selectivity.A model is presented to account for the origin of the selectivity together with a possible mechanism for the reduction.
- Davey, Claire L.,Powell, Lawson W.,Turner, Nicholas J.,Wells, Andrew
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p. 7867 - 7870
(2007/10/02)
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- THE NUCLEOPHILIC AROMATIC PHOTOSUBSTITUTIONS OF 4,5-DINITROVERATROLE WITH AMINES. PHOTOREDUCTIONS OF AROMATIC DINITROCOMPOUNDS
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4,5-Dinitroveratrole is effectively photosubstituted by amines with relatively high ionization potential such as methylamine, n-butylamine and ethyl glycinate, but is mainly photoreduced when amines with relatively low ionization potential, such as dimethyl or trimethylamine are used.The photoreduction of several aromatic dinitrocompounds by triethylamine gives nitroanilines.A mechanistic scheme is proposed embracing our photosubstitutions and photoreductions, based on our experimental results and on MINDO/3 calculations of the ground states and the more likely intermediates.
- Marquet, Jorge,Moreno-Manas, Marcial,Vallribera, Adelina,Virgili, Albert,Bertran, Joan,et al.
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p. 351 - 360
(2007/10/02)
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