111398-44-8Relevant articles and documents
Design and synthesis of novel symmetric fluorene-2,7-diamine derivatives as potent hepatitis C virus inhibitors
Mousa, Mai H. A.,Ahmed, Nermin S.,Schwedtmann, Kai,Frakolaki, Efseveia,Vassilaki, Niki,Zoidis, Grigoris,Weigand, Jan J.,Abadi, Ashraf H.
, (2021)
Hepatitis C virus (HCV) is an international challenge. Since the discovery of NS5A direct-acting antivirals, researchers turned their attention to pursue novel NS5A inhibitors with optimized design and structure. Herein we explore highly potent hepatitis C virus (HCV) NS5A inhibitors; the novel analogs share a common symmetrical prolinamide 2,7-diaminofluorene scaffold. Modification of the 2,7-diaminofluorene backbone included the use of (S)-prolinamide or its isostere (S,R)-piperidine-3-caboxamide, both bearing different amino acid residues with terminal carbamate groups. Compound 26 exhibited potent inhibitory activity against HCV genotype (GT) 1b (effective concentration (EC50) = 36 pM and a selectivity index of >2.78 × 106). Compound 26 showed high selectivity on GT 1b versus GT 4a. Interestingly, it showed a significant antiviral effect against GT 3a (EC50 = 1.2 nM). The structure-activity relationship (SAR) analysis revealed that picomolar inhibitory activity was attained with the use of S-prolinamide capped with R- isoleucine or R-phenylglycine residues bearing a terminal alkyl carbamate group.
Preparation process of amino acid N-carboxylic acid anhydride
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Paragraph 0050-0053, (2021/06/06)
The invention provides a preparation process of amino acid N-carboxylic acid anhydride, which comprises the following operations: amino acid and methyl chloroformate are used as starting raw materials to react under an alkaline condition to generate N-methoxycarbonyl-amino acid, and the N-methoxycarbonyl-amino acid is separated and purified under an acidic condition; dissolving the purified and dried N-methoxycarbonyl-amino acid in a solvent, mixing with a ring closing reagent thionyl chloride, and reacting at a certain reaction temperature to generate an amino acid N-carboxylic acid anhydride crude product; and adding a good solvent into the obtained amino acid N-carboxylic acid anhydride crude product, filtering to remove impurities, adding a poor solvent into the filtrate, recrystallizing under freezing, and drying to obtain the amino acid N-carboxylic acid anhydride (NCA). The preparation process is simple and convenient in method, easy to purify, stable in process, controllable in quality, low in anhydrous requirement on a reaction system, greatly improved in product yield, greatly reduced in reaction risk and suitable for industrial mass production.
Compounds for inhibiting HCV (hepatitis C virus), pharmaceutical composition and application of compounds or pharmaceutical composition
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Paragraph 0095; 0096; 0097, (2019/02/04)
The invention discloses compounds for inhibiting HCV (hepatitis C virus), pharmaceutical composition and an application of the compounds or the pharmaceutical composition. The compounds are compoundsshown in formula (I) or a stereoisomer, geometric isomer, a tautomer, an enantiomer, sulfur oxide, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compounds shown in formula (I); the compounds are effective antiviral drugs, especially can be used for inhibiting the function of NS5A protein encoded by the HCV, thereby effectively inhibiting the HCV.The method for preventing and/or treating drugs or diseases associated with the HCV by the compounds or the composition containing the new compounds has good market development prospects.
