- Design, synthesis and biological evaluation of novel oseltamivir derivatives as potent neuraminidase inhibitors
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Neuraminidase (NA) is one of the particular potential targets for novel antiviral therapy. In this work, a series of neuraminidase inhibitors with the cyclohexene scaffold were studied based upon the combination of 3D-QSAR, molecular docking, and molecular dynamics techniques. The results indicate that the built 3D-QSAR models yield reliable statistical information: the correlation coefficient (r2) and cross-validation coefficient (q2) of CoMFA (comparative molecular field analysis) are 0.992 and 0.819; the r2 and q2 of CoMSIA (comparative molecular similarity analysis) are 0.992 and 0.863, respectively. Molecular docking and MD simulations were conducted to confirm the detailed binding mode of enzyme-inhibitor system. The new NA inhibitors had been designed, synthesized, and their inhibitory activities against group-1 neuraminidase were determined. One agent displayed excellent neuraminidase inhibition, with IC50 value of 39.6 μM against NA, while IC50 value for oseltamivir is 61.1 μM. This compound may be further investigated for the treatment of infection by the new type influenza virus.
- Wang, Zhen,Cheng, Li Ping,Zhang, Xing Hua,Pang, Wan,Li, Liang,Zhao, Jin Long
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Read Online
- Nickel- and Palladium-Catalyzed Cross-Coupling of Stibines with Organic Halides: Site-Selective Sequential Reactions with Polyhalogenated Arenes
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Herein, we disclose a general and efficient method for the synthesis of Sb-aryl and Sb-alkyl stibines by the nickel-catalyzed cross-coupling of halostibines with organic halides. The synthesized Sb-aryl stibines couple with aryl halides to give biaryls efficiently via palladium catalysis. Sequential reactions of stibines with polyhalogenated arenes bearing active C–I/C–Br sites and inactive C–Cl sites successfully proceeded, resulting in the formation of a variety of complex molecules with good site selectivity. Drugs such as diflunisal and fenbufen, as well as a fenofibrate derivative, were synthesized on gram scales in good yields, together with the high recovery of chlorostibine. Furthermore, catalytic mechanisms are proposed based on the results of control experiments.
- Ghaderi, Arash,Kambe, Nobuaki,Le, Liyuan,Lu, Hao,Qiu, Renhua,Tang, Ting,Tong, Zhou,Wong, Wai-Yeung,Xu, Zhi,Yin, Shuang-Feng,Zeng, Dishu,Zhang, Dejiang,Zhang, Zhao
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p. 854 - 867
(2022/01/19)
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- Gold Catalysts Can Generate Nitrone Intermediates from a Nitrosoarene/Alkene Mixture, Enabling Two Distinct Catalytic Reactions: A Nitroso-Activated Cycloheptatriene/Benzylidene Rearrangement
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Gold-catalyzed reactions of cycloheptatrienes with nitrosoarenes yield nitrone derivatives efficiently. This reaction sequence enables us to develop gold-catalyzed aerobic oxidations of cycloheptatrienes to afford benzaldehyde derivatives using CuCl and nitrosoarenes as co-catalysts (10-30 mol %). Our density functional theory calculations support a novel nitroso-activated rearrangement, tropylium → benzylidene. With the same nitrosoarenes, we developed their gold-catalyzed [2 + 2 + 1]-annulations between nitrosobenzene and two enol ethers to yield 5-alkoxyisoxazolidines using 1,4-cyclohexadienes as hydrogen donors.
- Cheng, Mu-Jeng,Kardile, Rahul Dadabhau,Kuo, Tung-Chun,Liu, Rai-Shung,More, Sayaji Arjun
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supporting information
p. 5506 - 5511
(2021/07/31)
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- The Discovery of Novel ACA Derivatives as Specific TRPM2 Inhibitors that Reduce Ischemic Injury Both in Vitro and in Vivo
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The transient receptor potential melastatin 2 (TRPM2) channel is associated with ischemia/reperfusion injury, inflammation, cancer, and neurodegenerative diseases. However, the limit of specific inhibitors impedes the development of TRPM2-targeted therapeutic agents. To discover more potent and selective TRPM2 inhibitors, 59 N-(p-amylcinnamoyl) anthranilic acid (ACA) derivatives were synthesized and evaluated using calcium imaging and electrophysiology approaches. Systematic structure-activity relationship studies resulted in some potent compounds inhibiting the TRPM2 channel with sub-micromolar half-maximal inhibitory concentration values. Among them, the preferred compound A23 exhibited TRPM2 selectivity over TRPM8 and TRPV1 channels as well as phospholipase A2 and showed neuroprotective activity in vitro. Following pharmacokinetic studies, A23 was further evaluated in a transient middle cerebral artery occlusion model in vivo, which significantly reduced cerebral infarction. These data indicate that A23 might serve as a useful tool for TRPM2-related research as well as a lead compound for the development of therapeutic agents for ischemic injury.
- Zhang, Han,Yu, Peilin,Lin, Hongwei,Jin, Zefang,Zhao, Siqi,Zhang, Yi,Xu, Qingxia,Jin, Hongwei,Liu, Zhenming,Yang, Wei,Zhang, Liangren
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p. 3976 - 3996
(2021/05/04)
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- Nickel- and Palladium-Catalyzed Cross-Coupling Reactions of Organostibines with Organoboronic Acids
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A strategy for the formation of antimony-carbon bond was developed by nickel-catalyzed cross-coupling of halostibines. This method has been applied to the synthesis of various triaryl- and diarylalkylstibines from the corresponding cyclic and acyclic halostibines. This protocol showed a wide substrate scope (72 examples) and was compatible to a wide range of functional groups such as aldehyde, ketone, alkene, alkyne, haloarenes (F, Cl, Br, I), and heteroarenes. A successful synthesis of arylated stibine 3 a in a scale of 34.77 g demonstrates high synthetic potential of this transformation. The formed stibines (R3Sb) were then used for the palladium-catalyzed carbon–carbon bond forming reaction with aryl boronic acids [R?B(OH)2], giving biaryls with high selectivity, even the structures of two organomoieties (R and R′) are very similar. Plausible catalytic pathways were proposed based on control experiments.
- Zhang, Dejiang,Le, Liyuan,Qiu, Renhua,Wong, Wai-Yeung,Kambe, Nobuaki
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supporting information
p. 3104 - 3114
(2020/12/11)
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- N,N′-bridged binuclear NHC palladium complexes: A combined experimental catalytic and computational study for the Suzuki reaction
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This work examines how N-donor bridged spacer ligands affect N-heterocyclic carbene (NHC) palladium complexes catalytic activities for Suzuki coupling reaction. Different degrees of structural flexibility binuclear NHC palladium complexes were synthesized. The more flexible nitrogen-based alkyl chain ligand shows similar performance with cycloamine counterparts in the Suzuki coupling reaction. Suzuki coupling examples were used in air and ambient temperature to reach moderate to completion yields in short time. Density functional theory calculations showed that the chelate effect, associated with a single Pd complex mechanism, plays a fundamental role in the pre-catalysis stage, supporting a reasonable of the kinetic activity observed experimentally.
- Chen, Ming-Tsz,Hsieh, Bing-Yan,Liu, Yi-Hung,Wu, Kuo-Hui,Lussari, Natália,Braga, Ataualpa A.C.
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- (N-Heterocyclic carbene) ion-pair palladium complexes: Suzuki–Miyaura cross-coupling studies in neat water under mild conditions
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The synthesis and characterization of a series of (N-heterocyclic carbene)PdCl3?(NMe3H)+ ion-pair complexes are presented. Applying the quaternary ammonium salt as the function with NHC–Pd(II) complexes yields the new ion-pair complexes. The NHC–Pd(II) ion-pair complexes work well by undergoing the Suzuki–Miyaura reaction with aryl chloride substrates in water under mild conditions in air at room temperature. Twenty products resulting from Suzuki–Miyaura coupling reactions carried out in the presence of the new NHC–Pd(II) ion-pair complex under mild optimal conditions were examined to determine the optimum yields.
- Chen, Ming-Tsz,Lin, Yu-Hsuan,Jian, Kun-Han
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- Cyclodextrin-supported palladium complex: A highly active and recoverable catalyst for Suzuki–Miyaura cross-coupling reaction in aqueous medium
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A water-soluble, cyclodextrin-supported palladium complex (DACH-Pd-β-CD) catalytic system was designed and synthesized, which can efficiently catalyze Suzuki–Miyaura cross-coupling reactions between aryl halides and arylboronic acid in water under mild conditions. The catalyst was successfully characterized using the methods of transmission electron microscopy, energy-dispersive X-ray spectrometry, X-ray diffraction, thermogravimetric analysis, and Fourier transform infrared and NMR spectroscopies. Furthermore, the catalyst can be easily separated from the reaction mixture and still maintain high catalytic activity after ten cycles. No leaching of palladium into the reaction solution occurred. The advantages of green solvent (water), short reaction times (2–6?h), low catalyst loading (0.001?mol%), excellent yields (up to 99%) and reusability of the catalyst mean it will have potential applications in green chemical synthesis.
- Guo, Yafei,Li, Jiuling,Shi, Xiwei,Liu, Yang,Xie, Kai,Liu, Yuqi,Jiang, Yubo,Yang, Bo,Yang, Rui
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- SYNTHESES OF METAL HETEROCYCLIC CARBENE ENOLATES AS COUPLING REACTIONS CATALYSTS
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The invention relates to the synthesis methods of N-heterocyclic carbene NHCE metal complexes and their catalytic activities in carbon-carbon coupling reactions.
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(2017/07/01)
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- An active catalytic system for Suzuki-Miyaura cross-coupling reactions using low levels of palladium loading
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An easily available Pd(OAc)2/(2-(anthracen-9-yl)-1H-inden-3-yl) dicyclohexylphosphine/toluene/iPrOH/water catalytic system was developed, which shows high catalytic activity in the Suzuki-Miyaura cross-coupling reactions of a diverse array of aryl and heteroaryl chlorides with Pd loadings down to 0.01 mol%.
- Yan, Meng-Qi,Yuan, Jia,Lan, Fang,Zeng, Si-Hao,Gao, Meng-Yue,Liu, Sheng-Hua,Chen, Jian,Yu, Guang-Ao
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supporting information
p. 3924 - 3929
(2017/07/10)
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- 2-Aryl-indenylphosphine ligands: Design, synthesis and application in Pd-catalyzed Suzuki-Miyaura coupling reactions
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A focused library of phosphine ligands was constructed for structural optimization. The catalyst can be used to perform the Suzuki-Miyaura cross-coupling reaction of aryl and heteroaryl chlorides.
- Lian, Ze-Yu,Yuan, Jia,Yan, Meng-Qi,Liu, Yan,Luo, Xue,Wu, Qing-Guo,Liu, Sheng-Hua,Chen, Jian,Zhu, Xiao-Lei,Yu, Guang-Ao
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supporting information
p. 10090 - 10094
(2016/11/06)
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- Metal-free iodination of arylboronic acids and the synthesis of biaryl derivatives
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A simple, general and efficient method is developed for the metal-free iodination of arylboronic acids. The protocol uses very cheap molecular iodine as the halide source and potassium carbonate as the base. The method is highly tolerant of various functional groups present in the substrates. Importantly, the iodination strategy can also be applied very effectively in the one-pot, two-step synthesis of biaryl derivatives. Georg Thieme Verlag Stuttgart New York.
- Niu, Liting,Zhang, Hao,Yang, Haijun,Fu, Hua
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supporting information
p. 995 - 1000
(2014/05/06)
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- Palladium nanoparticle catalysis: Borylation of aryl and benzyl halides and one-pot biaryl synthesis via sequential borylation-Suzuki-Miyaura coupling
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Palladium nanoparticles generated in PEG catalyze the reaction of bis(pinacolato)diboron with various aryl/benzyl halides to afford aryl/benzyl boronates in high yield. Arylboronates thus prepared, have been directly used in the Suzuki-Miyaura coupling reaction with different aryl halides and benzyl halides in a convenient one-pot, two-step solvent free green synthesis of unsymmetrical biaryls and diarylmethanes. The Royal Society of Chemistry 2012.
- Bej, Ansuman,Srimani, Dipankar,Sarkar, Amitabha
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experimental part
p. 661 - 667
(2012/05/04)
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- An efficient palladium-benzimidazolyl phosphine complex for the Suzuki-Miyaura coupling of aryl mesylates: Facile ligand synthesis and metal complex characterization
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A new class of easily accessible hemilabile benzimidazolyl phosphine ligands has been developed. The ligand skeleton is prepared from commercially available and inexpensive o-phenylenediamine and 2-bromobenzoic acid. With catalyst loading down to 0.5 mol% palladium, excellent catalytic activity towards the Suzuki-Miyaura coupling of aryl mesylates is still observed. This represents the lowest catalyst loading achieved so far for this reaction in general. X-Ray crystallography shows that new ligand L2 is coordinated with Pd in a κ2-P,N fashion.
- Chung, Kin Ho,So, Chau Ming,Wong, Shun Man,Luk, Chi Him,Zhou, Zhongyuan,Lau, Chak Po,Kwong, Fuk Yee
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supporting information; experimental part
p. 1967 - 1969
(2012/03/10)
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- Rapid nickel-catalyzed suzuki-miyaura cross-couplings of aryl carbamates and sulfamates utilizing microwave heating
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High-speed and scalable nickel-catalyzed cross-coupling of arylboronic acids with aryl carbamates and sulfamates is achieved by using sealed-vessel microwave processing.(Figure Presented)
- Baghbanzadeh, Mostafa,Pilger, Christian,Kappe, C. Oliver
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supporting information; experimental part
p. 1507 - 1510
(2011/04/26)
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- PIPERIDINES USEFUL FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISORDERS
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The invention relates to compounds which are substituted chiral or achiral derivatives of 3- or 4- aminopiperidine of the general formula (I). The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of general formula I and especially their use as inhibitors of β-secretases.
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- SUBSTITUTED 3- AND 4- AMINOMETHYLPIPERIDINES FOR USE AS BETA-SECRETASE IN THE TREATMENT OF ALZHEIMER’S DISEASE
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The invention relates to novel compounds, which are substituted chiral or achiral derivatives of 3- or 4- aminomethylpiperidine of the general formula (I). The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of general formula (I) and especially their use as inhibitors of beta-secretases for the treatment of Alzheimer’s disease.
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