- Optimization of N-Substituted Oseltamivir Derivatives as Potent Inhibitors of Group-1 and -2 Influenza A Neuraminidases, Including a Drug-Resistant Variant
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On the basis of our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Among the synthesized compounds, 15b and 15c were exceptionally active against both group-1 and -2 NAs. Especially for 09N1, N2, N6, and N9 subtypes, they showed 6.80-12.47 and 1.20-3.94 times greater activity than oseltamivir carboxylate (OSC). They also showed greater inhibitory activity than OSC toward H274Y and E119V variant. In cellular assays, they exhibited greater potency than OSC toward H5N1, H5N2, H5N6, and H5N8 viruses. 15b demonstrated high metabolic stability, low cytotoxicity in vitro, and low acute toxicity in mice. Computational modeling and molecular dynamics studies provided insights into the role of R group of 15b in improving potency toward group-1 and -2 NAs. We believe the successful exploitation of the 150-cavity of NAs represents an important breakthrough in the development of more potent anti-influenza agents.
- Zhang, Jian,Poongavanam, Vasanthanathan,Kang, Dongwei,Bertagnin, Chiara,Lu, Huamei,Kong, Xiujie,Ju, Han,Lu, Xueyi,Gao, Ping,Tian, Ye,Jia, Haiyong,Desta, Samuel,Ding, Xiao,Sun, Lin,Fang, Zengjun,Huang, Boshi,Liang, Xuewu,Jia, Ruifang,Ma, Xiuli,Xu, Wenfang,Murugan, Natarajan Arul,Loregian, Arianna,Huang, Bing,Zhan, Peng,Liu, Xinyong
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Read Online
- Pd/AlO(OH): A Heterogeneous, Stable and Recyclable Catalyst for N-Arylation of Aniline Under Ligand-Free Aerobic Condition
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Abstract: Many synthetic methods have been reported to construct an aryl-nitrogen bond. But they mainly suffer from the usage of expensive ligands. Herein, we report highly effective, heterogeneous, reusable and ligand-free nanocatalyst for the Buchwald-Hartwig coupling reaction under aerobic condition. Wafer-like structure with nano-porous nature of AlO(OH) was identified with TEM and BET surface area analyses. Zero valent Pd nanoparticles (with less than 10?nm crystallite size which strongly evident from TEM analysis) were observed in XRD pattern, which was further confirmed by XPS studies. The reaction conditions were optimized and the scope of the reaction was extended with various aryl halides and aniline using low amount of Pd (0.31?mol%) based heterogeneous catalyst. Heterogeneity, reusability and stability (confirmed by XRD) were found to be reasonable. Use of meagre amount of Pd and the ligand-free aerobic condition make this system economically as well as environmentally feasible. Graphical Abstract: [Figure not available: see fulltext.].
- Ganesh Babu, Sundaram,Emayavaramban, Balakumar,Jerome, Peter,Karvembu, Ramasamy
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Read Online
- Reductive C?N Coupling of Nitroarenes: Heterogenization of MoO3 Catalyst by Confinement in Silica
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The construction of C?N bonds with nitroaromatics and boronic acids using highly efficient and recyclable catalysts remains a challenge. In this study, nanoporous MoO3 confined in silica serves as an efficient heterogeneous catalyst for C?N cross-coupling of nitroaromatics with aryl or alkyl boronic acids to deliver N-arylamines and with desirable multiple reusability. Experimental results suggest that silica not only heterogenizes the Mo species in the confined mesoporous microenvironment but also significantly reduces the reaction induction period and regulates the chemical efficiency of the targeted product. The well-shaped MoO3@m?SiO2 catalyst exhibits improved catalytic performance both in yield and turnover number, in contrast with homogeneous Mo catalysts, commercial Pd/C, or MoO3 nanoparticles. This approach offers a new avenue for the heterogeneous catalytic synthesis of valuable bioactive molecules.
- Yang, Fu,Dong, Xuexue,Shen, Yang,Liu, Mengting,Zhou, Hu,Wang, Xuyu,Li, Lulu,Yuan, Aihua,Song, Heng
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p. 3413 - 3421
(2021/07/31)
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- BTK INHIBITOR
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Provided are a series of BTK inhibitors, and specifically disclosed are a compound, pharmaceutically acceptable salt thereof, tautomer thereof or prodrug thereof represented by formula (I), (II), (III) or (IV).
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Paragraph 0266-0267
(2017/11/16)
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- Copper immobilized on magnetite nanoparticles coated with ascorbic acid: An efficient and reusable catalyst for C─N and C─O cross-coupling reactions
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In a continuation of using magnetic nanoparticle (MNP)-supported catalysts, ascorbic acid (readily available, very safe and with strong affinity to MNPs) was used instead of the commonly used silica layer coating. This hybrid was used for immobilizing copper nanoparticles to produce Cu/ascorbic acid@MNPs catalyst. The catalyst was characterized and used in carbon–oxygen and carbon–nitrogen (various substrates) cross-coupling reactions in aqueous media and at room temperature with excellent product yields. Furthermore, the catalyst could be quickly and completely recovered using an external magnetic field and reused for six reaction cycles without significant change in catalytic activity.
- Hajipour, Abdol R.,Check, Maryam,Khorsandi, Zahra
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- METHOD FOR COUPLING A FLUOROSULFONATE COMPOUND WITH AN AMINE COMPOUND
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The present disclosure describes a method of coupling a first compound to a second compound, the method comprising: providing the first compound having a fluorosulfonate substituent; providing the second compound comprising an amine; and reacting the first compound and the second compound in a reaction mixture, the reaction mixture including a catalyst having at least one group 10 atom, the reaction mixture under conditions effective to couple the first compound to the second compound. The present disclosure further describes a one-pot method for coupling a first compound to a second compound.
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Paragraph 0050-0051
(2016/05/02)
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- OXACAZONE COMPOUNDS TO TREAT CLOSTRIDIUM DIFFICILE
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Compounds, compositions, and methods for treating C. difficile are provided.
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Page/Page column 86
(2016/04/04)
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- Palladium- and Nickel-Catalyzed Amination of Aryl Fluorosulfonates
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Examples of the palladium- and nickel-catalyzed amination of aryl fluorosulfonates with aromatic and alkyl amines are described. Aniline is coupled to a diverse series of aryl fluorosulfonates catalyzed by the combination of CpPd(cinammyl) and Xantphos, and the relative reactivity of aryl fluorosulfonates to undergo Pd-catalyzed amination was compared with other common aryl electrophiles. In addition, we report the direct amination of a phenol by in situ formation of an aryl fluorosulfonate by reaction with sulfuryl fluoride and base followed by subsequent amination to form a new C-N bond. Finally, we report examples of the nickel-catalyzed amination of aryl fluorosulfonates catalyzed by the combination of Ni(COD)2 and DPPF in the presence of MeCN. The high reactivity of the aryl fluorosulfonate electrophile with generic palladium and nickel catalyst systems, combined with its simple preparation from sulfuryl fluoride will enable commercial amination reactions of abundant phenolic raw materials.
- Hanley, Patrick S.,Clark, Thomas P.,Krasovskiy, Arkady L.,Ober, Matthias S.,O'Brien, John P.,Staton, Tina S.
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p. 3515 - 3519
(2016/07/06)
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- Synthesis of polyfunctional secondary amines by the addition of functionalized zinc reagents to nitrosoarenes
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Addition of functionalized aryl, heteroaryl or adamantyl zinc reagents to various nitroso-arenes in the presence of magnesium salts and LiCl in THF produces after a reductive work-up with FeCl2 and NaBH4 in ethanol the corresponding polyfunctional secondary amines in high yields. This journal is
- Dhayalan, Vasudevan,S?mann, Christoph,Knochel, Paul
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supporting information
p. 3239 - 3242
(2015/06/01)
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- Efficient and versatile buchwald-hartwig amination of (hetero)aryl chlorides using the Pd-PEPPSI-IPr(NMe2)2 precatalyst in the presence of carbonate base
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The precatalyst Pd-PEPPSI-IPr(NMe2)2, in which the IPr ligand was modified by attachment of two dimethylamino groups on to the 4- and 5-positions of the imidazolyl heterocycle, was found to show high catalytic efficiency in the Buchwald-Hartwig amination under mild conditions using Cs2CO3 as a weak base, using a low catalyst loading of 1 mol-%. The protocol is applicable to aryl chlorides bearing base-sensitive substituents, as exemplified by the coupling of 4-chloroacetophenone with aniline. It can also be used with an unprecedentedly wide range of amines, including strongly basic secondary alkylamines, primary arylamines, and primary alkylamines. The Palladium precatalyst Pd-PEPPSI-IPr(NMe2)2, whose supporting N-heterocyclic carbene ligand was decorated with two dimethylamino groups, was found to catalyse the Buchwald-Hartwig amination of aryl halides with a wide range of amines under mild conditions using cesium carbonate as base.
- Zhang, Yin,César, Vincent,Lavigne, Guy
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p. 2042 - 2050
(2015/03/18)
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- Smiles rearrangement for the synthesis of diarylamines
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A protocol for the one-pot synthesis of diarylamines via Smiles rearrangement under microwave irradiation has been developed. Various diarylamines were effectively synthesized starting from readily available substituted phenols, arylamines and chloroacetyl chloride in moderate to good yields (58-92%). ARKAT-USA, Inc.
- Tian, Xiao,Wu, Ren-Min,Liu, Gang,Li, Zhu-Bo,Wei, He-Lin,Yang, Hao,Shin, Dong-Soo,Wang, Li-Ying,Zuo, Hua
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experimental part
p. 118 - 126
(2011/10/02)
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- A new class of easily activated palladium precatalysts for facile C-N cross-coupling reactions and the low temperature oxidative addition of aryl chlorides
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A new class of one-component Pd precatalysts bearing biarylphosphine ligands is described. These precatalysts are air- and thermally stable, are easily activated under normal reaction conditions at or below room temperature, and ensure the formation of the highly active monoligated Pd(0) complex necessary for oxidative addition. The use of these precatalysts as a convenient source of LPd(0) in C-N cross-coupling reactions is explored. The reactivity that is demonstrated in this study is unprecedented in palladium chemistry. Copyright
- Biscoe, Mark R.,Fors, Brett P.,Buchwald, Stephen L.
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p. 6686 - 6687
(2008/12/22)
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- Heterocycles substituted pyridine derivatives and antifungal agent containing thereof
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An object of the present invention is to provide an antifungal agent which has excellent antifungal effects and is superior in terms of its physical properties, safety and metabolic stability. According to the present invention, there is disclosed a compound represented by the following formula (I), or a salt thereof: wherein R1 represents a hydrogen atom, a halogen atom, an amino group, a C1-6 alkyl group, a C1-6 alkoxy group or a C1-6 alkoxy C1-6 alkyl group; R2 represents a hydrogen atom, a C1-6 alkyl group, an amino group or a di C1-6 alkylamino group; one of X and Y is a nitrogen atom while the other is a nitrogen atom or an oxygen atom; ring A represents a 5- or 6-member heteroaryl ring or a benzene ring which may have a halogen atom, or 1 or 2 C1-6 alkyl groups; Z represents a single bond, a methylene group, an ethylene group, an oxygen atom, a sulfur atom, —CH2O—, —OCH2—, —NH—, —CH2NH—, —NHCH2—, —CH2S—, or —SCH2—; R3 represents a hydrogen atom, a halogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 5- or 6-member heteroaryl group, or 5- or 6-member non-aromatic heterocyclic group which may have 1 or 2 substituents; and R4 represents a hydrogen atom or a halogen atom.
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Page/Page column 122-123
(2010/11/27)
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- Photochemical formylation of carbazole and diphenylamine
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Carbazole (1) and diphenylamine (7) undergo photo-chemical formylation in chloroform solution to furnish the corresponding formyl derivatives 2, 3 and 8, 9 respectively. The reaction has been successfully extended to 1-methylcarbazole (4) to yield formyl derivatives 5 and 6.
- Chowdhury,Saha,Podder
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p. 405 - 406
(2007/10/02)
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