- Novel N-Substituted oseltamivir derivatives as potent influenza neuraminidase inhibitors: Design, synthesis, biological evaluation, ADME prediction and molecular docking studies
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The discovery of novel potent neuraminidase (NA) inhibitors remains an attractive approach for treating infectious diseases caused by influenza. In this study, we describe the design and synthesis of novel N-substituted oseltamivir derivatives for probing the 150-cavity which is nascent to the activity site of NA. NA inhibitory studies showed that new derivatives demonstrated the inhibitory activity with IC50 values at nM level against NA of a clinical influenza virus strain. Moreover, the in silico ADME predictions showed that the selected compounds had comparable properties with oseltamivir carboxylate, which demonstrated the druggablity of these derivatives. Furthermore, molecular docking studies showed that the most potent compound 6f and 10i could adopt different modes of binding interaction with NA, which may provide novel solutions for treating oseltamivir-resistant influenza. Based on the research results, we consider that compounds 6f and 10i have the potential for further studies as novel antiviral agents.
- Ye, Jiqing,Yang, Xiao,Xu, Min,Chan, Paul Kay-sheung,Ma, Cong
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supporting information
(2019/09/06)
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- Aminopyrimidine Kinase Inhibitors
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Disclosed are compounds, pharmaceutical compositions containing those compounds, and uses of the compounds and compositions as modulators of casein kinase 1 (e.g., CK1γ), casein kinase 2 (CK2), Pim-1, Pim-2, Pim-3, the TGFβ pathway, the Wnt pathway, the J
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Page/Page column 81
(2012/11/07)
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- Palladium membrane-installed microchannel devices for instantaneous Suzuki-Miyaura cross-coupling
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Instantaneous catalytic carbon-carbon bond-forming reactions were achieved in catalytic membrane-installed microchannel devices that have a polymeric palladium-complex membrane. The catalytic membrane-installed microchannel devices were provided inside the microchannels by means of coordinative and ionic molecular convolution at the interface between the organic and aqueous phases flowing laminarly, in which both non-crosslinked linear polymer ligands and palladium species dissolved. The palladium-catalyzed Suzuki-Miyaura reaction of aryl, heteroaryl, and alkenyl halides with arylboronic acids and sodium tetraarylborates was performed with the catalytic membrane-installed microchannel devices to give quantitative yields of biaryls, heterobiaryls, and aryl alkenes within 5 s of residence time in the defined channel region. These microchannel devices were applied to the instantaneous allylic aryla-tion reaction of allylic esters with aryl-boron reagents under microflow conditions to afford the corresponding coupling products within 1 s of residence time.
- Yamada, Yoichi M. A.,Watanabe, Toshihiro,Beppu, Tomohiko,Fukuyama, Naoshi,Torii, Kaoru,Uozumi, Yasuhiro
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experimental part
p. 11311 - 11319
(2010/11/04)
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