262853-93-0Relevant articles and documents
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Freifelder
, p. 1135 (1963)
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Proline-Based Allosteric Inhibitors of Zika and Dengue Virus NS2B/NS3 Proteases
Millies, Benedikt,Von Hammerstein, Franziska,Gellert, Andrea,Hammerschmidt, Stefan,Barthels, Fabian,G?ppel, Ulrike,Immerheiser, Melissa,Elgner, Fabian,Jung, Nathalie,Basic, Michael,Kersten, Christian,Kiefer, Werner,Bodem, Jochen,Hildt, Eberhard,Windbergs, Maike,Hellmich, Ute A.,Schirmeister, Tanja
, p. 11359 - 11382 (2019/12/24)
The NS2B/NS3 serine proteases of the Zika and Dengue flaviviruses are attractive targets for the development of antiviral drugs. We report the synthesis and evaluation of a new, proline-based compound class that displays allosteric inhibition of both proteases. The structural features relevant for protease binding and inhibition were determined to establish them as new lead compounds for flaviviral inhibitors. Based on our structure-activity relationship studies, the molecules were further optimized, leading to inhibitors with submicromolar IC50 values and improved lipophilic ligand efficiency. The allosteric binding site in the proteases was probed using mutagenesis and covalent modification of the obtained cysteine mutants with maleimides, followed by computational elucidation of the possible binding modes. In infected cells, antiviral activity against Dengue virus serotype 2 using prodrugs of the inhibitors was observed. In summary, a novel inhibitor scaffold targeting an allosteric site shared between flaviviral NS2B/NS3 proteases is presented whose efficacy is demonstrated in vitro and in cellulo.
AN ECO-FRIENDLY PROCESS FOR HYDROGENATION OR/AND HYDRODEOXYGENATION OF ORGANIC COMPOUND USING HYDROUS RUTHENIUM OXIDE CATALYST
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Page/Page column 15; 22, (2017/08/01)
The invention discloses aneco-friendly process for hydrogenation (alkenealkene, carbonyl compound and aromatic) and hydrodeoxygenation (methoxy phenols) of organic compound using hydrous ruthenium oxide (HRO) and its supported form as a recyclable heterogeneous catalyst in aqueous medium with good yield of desired compounds (70-100%) under mild reaction conditions. The invention also discloses hydrogenation of organic compound such as alkene, carbonyl compound and substituted aromatic and also for the processes that involve hydrodeoxygenation, for example, lignin derived aromatic (methoxy phenols).