- Peramivir impurity A and impurity C, and preparation methods and application thereof
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The invention discloses a peramivir impurity A and a peramivir impurity C with structures as shown in the specification. The invention also provides synthesis methods of the impurity A and the impurity C, and application of the impurity A and the impurity C as impurity reference substances in quality control of peramivir or a pharmaceutical composition thereof. The impurities can be stably prepared and supplied, and a basis is provided for related research and contrast. The peramivir impurity A and the peramivir impurity C disclosed by the invention have important significance in controlling peramivir raw material medicines and researching impurities of preparations of the peramivir raw material medicines.
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Paragraph 0017; 0061; 0067-0068; 0074; 0080-0081
(2022/01/12)
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- Peramivir intermediate 9 impurity F as well as preparation method and application thereof
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The invention provides a peramivir intermediate 9 impurity F. The structural formula of the peramivir intermediate 9 impurity F is shown as a formula (I). The preparation method of the peramivir intermediate 9 impurity F comprises the following steps: A, performing reduction reaction on a peramivir intermediate 8 and a reducing agent in an organic solvent and an acid solution at the reaction temperature of -20 DEG C to 100 DEG C for 2-10 hours to obtain a reaction solution; and B, concentrating the reaction solution under reduced pressure to obtain a crude product of the impurity F of the peramivir intermediate 9, and conducting purifying to obtain the impurity F of the peramivir intermediate 9. Through research on peramivir impurities, the brand-new peramivir intermediate 9 impurity F isobtained, through mass spectrometry, the MS has a [M+1] peak 359.26, the corresponding molecular weight is 358.25, the purity reaches 90.0% or above, the impurity F can be used as a reference substance for impurity research for peramivir content determination, and the medication safety of peramivir can be effectively guaranteed.
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Paragraph 0014; 0031-0038
(2021/01/28)
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- Peramivir Phosphonate Derivatives as Influenza Neuraminidase Inhibitors
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Peramivir is a potent neuraminidase (NA) inhibitor for treatment of influenza infection by intravenous administration. By replacing the carboxylate group in peramivir with a phosphonate group, phosphono-peramivir (6a), the dehydration and deoxy derivatives (7a and 8a) as well as their corresponding monoalkyl esters are prepared from a pivotal intermediate epoxide 12. Among these phosphonate compounds, the dehydration derivative 7a that has a relatively rigid cyclopentene core structure exhibits the strongest inhibitory activity (IC50 = 0.3-4.1 nM) against several NAs of wild-type human and avian influenza viruses (H1N1, H3N2, H5N1, and H7N9), although the phosphonate congener 6a is unexpectedly less active than peramivir. The inferior binding affinity of 6a is attributable to the deviated orientations of its phosphonic acid and 3-pentyl groups in the NA active site as inferred from the NMR, X-ray diffraction, and molecular modeling analyses. Compound 7a is active to the oseltamivir-resistant H275Y strains of H1N1 and H5N1 viruses (IC50 = 73-86 nM). The phosphonate monoalkyl esters (6b, 6c, 7b, 7c, 8b, and 8c) are better anti-influenza agents (EC50 = 19-89 nM) than their corresponding phosphonic acids (EC50 = 50-343 nM) in protection of cells from the viral infection. The phosphonate monoalkyl esters are stable in buffer solutions (pH 2.0-7.4) and rabbit serum; furthermore, the alkyl group is possibly tuned to attain the desired pharmacokinetic properties.
- Wang, Peng-Cheng,Fang, Jim-Min,Tsai, Keng-Chang,Wang, Shi-Yun,Huang, Wen-I,Tseng, Yin-Chen,Cheng, Yih-Shyun E.,Cheng, Ting-Jen Rachel,Wong, Chi-Huey
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p. 5297 - 5310
(2016/07/06)
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- Facile synthesis of the neuraminidase inhibitor peramivir
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An improved and convenient synthetic route for the synthesis of peramivir has been developed with a total 34% yield. The process was improved from previous methods in three key reaction steps including 1,3-dipolar cycloaddition, reductive ring cleavage of
- Jia, Fei,Hong, Juan,Sun, Ping-Hua,Chen, Jian-Xin,Chen, Wei-Min
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p. 2641 - 2647
(2013/07/26)
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- (1S, 2S, 3S, 4R)-3-Y(1S)-1-ACETYLAMINO-2-ETHYL-BUTYL¨-4-GUANIDINO-2- HYDROXYL-CYCLOPENTYL-1-CARBOXYLIC ACID HYDRATES AND PHARMACEUTICAL USES THEREOF
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The present invention relates to (1S,2S,3S,4R)-3-[(1S)-1-acetylamino-2-ethyl-butyl]-4-guanidino-2-hydroxy-cyclopentyl-1-carboxylic acid hydrates compounds, preparing methods thereof, pharmaceutical compositions containing said compounds and preparing methods thereof, and the clinical uses of said compounds as neuramidinase inhibitors for anti-influenza.
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Page/Page column 5-6; 12
(2010/06/15)
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- Process for preparing substituted cyclopentane derivatives and novel crystalline structures thereof
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The invention relates to a process for preparing substituted cyclopentane derivatives represented by the wherein R1, R2, R3, R4, X and Y are as described in the specification, and pharmaceutically acceptable salts thereof. The invention further relates to a process for purifying the compound of formula (Ia) and novel crystalline forms of the compound of formula (Ia).
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