Xi:Irritant;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.
Method for preparing (S)-3-piperidinecarboxylic acid
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Paragraph 0025-0030; 0036; 0039; 0041, (2017/08/29)
The invention discloses a method for preparing (S)-3-piperidinecarboxylic acid. The method includes steps of carrying out reaction on 3-piperidinecarboxamide or salt of the 3-piperidinecarboxamide in concentrated hydrochloric acid to obtain (S)-3-piperidinecarboxylic acid salt; converting the (S)-3-piperidinecarboxylic acid salt to obtain the (S)-3-piperidinecarboxylic acid. The method has the advantages that the reaction is carried out on the 3-piperidinecarboxamide or the salt of the 3-piperidinecarboxamide in the concentrated hydrochloric acid, accordingly, chiral resolution effects can be realized while hydrolysis is carried out, and resolution on the 3-piperidinecarboxamide or 3-piperidinecarboxylic acid by the aid of chiral resolving agents can be omitted; preparation processes are simple in post-treatment operation, N protection and de-protection processes are omitted, accordingly, the method is high in atomic economy and low in cost, and a simple, feasible and low-cost production method can be provided for synthesizing the (S)-3-piperidinecarboxylic acid.
