- Method for preparing oseltamivir intermediate
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The invention relates to a preparation method of an oseltamivir intermediate (as shown in a formula IV). The method is prepared through a route as described in the specification. The method is simple and safe to operate, short in synthetic route, high in yield, small in environmental pollution, good in economic effect and suitable for industrial production.
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Paragraph 0031-0034; 0039-0071
(2021/06/26)
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- Crystallization method of intermediate 5 of high-purity oseltamivir phosphate
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5 (Pentane 5 -yloxy) -3 - oxo -7 - bicyclo [-] hep 4.1.0-3 -3 - carboxylate ethyl carboxylate is concentrated to precipitate crystals, and then crystals are directly put into a mixed solvent composed of an alkane solvent and an alcohol solvent. Through the crystallization method, the purity of the intermediate 5 can reach above 99.7%, and the requirement for preparing oseltamivir phosphate is completely met.
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Paragraph 0016-0017; 0023; 0025-0038
(2021/10/27)
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- METHOD FOR PREVENTING OR TREATING ARRHYTHMIA, METHOD FOR PREVENTING OR TREATING ATRIAL FIBRILLATION, MODEL OF SUSTAINED ATRIAL FIBRILLATION, METHOD FOR PRODUCING THE MODEL, AND METHOD FOR SCREENING FOR ATRIAL FIBRILLATION INHIBITOR
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A method for preventing or treating atrial fibrillation, including: administering, to an individual, an atrial fibrillation inhibitor containing a compound expressed by one of the following Structural Formulas (I) to (VI) or a pharmacologically acceptable salt thereof: where in the Structural Formula (III), Gluc refers to glucuronic acid,
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Paragraph 0096; 0097
(2014/03/24)
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- Synthesis and in vitro study of novel neuraminidase inhibitors against avian influenza virus
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Evidences of oseltamivir resistant influenza patients raised the need of novel neuraminidase inhibitors. In this study, five oseltamivir analogs PMC-31-PMC-36, synthesised according to the outcomes of a rational design analysis aimed to investigate the effects of substitution at the 5-amino and 4-amido groups of oseltamivir on its antiviral activity, were screened for their inhibition against neuraminidase N1 and N3. The enzymes used as models were from the avian influenza A H7N1 and H7N3 viruses. The neuraminidase inhibition assay was carried out by using recombinant species obtained from a baculovirus expression system and the fluorogenic substrate MUNANA. The assay was validated by using oseltamivir carboxylate as a reference inhibitor. Among the tested compounds, PMC-36 showed the highest inhibition on N1 with an IC50 of 14.6 ± 3.0 nM (oseltamivir 25 ± 4 nM), while PMC-35 showed a significant inhibitory effect on N3 with an IC50 of 0.1 ± 0.03 nM (oseltamivir 0.2 ± 0.02 nM). The analysis of the inhibitory properties of this panel of compounds allowed a preliminary assessment of a structure-activity relationship for the modification of the 4-amido and 5-amino groups of oseltamivir carboxylate. The substitution of the acetamido group in the oseltamivir structure with a 2-butenylamido moiety reduced the observed activity, while the introduction of a propenylamido group was well tolerated. Substitution of the free 5-amino group of oseltamivir carboxylate with an azide, decreased the activity against both N1 and N3. When these structural changes were both introduced, a dramatic reduction of activity was observed for both N1 and N3. The alkylation of the free 5-amino group in oseltamivir carboxylate introducing an isopropyl group seemed to increase the inhibitory effect for both N1 and N3 neuraminidases, displaying a more pronounced effect against N1.
- Kongkamnerd, Jarinrat,Cappelletti, Luca,Prandi, Adolfo,Seneci, Pierfausto,Rungrotmongkol, Thanyada,Jongaroonngamsang, Nutthapon,Rojsitthisak, Pornchai,Frecer, Vladimir,Milani, Adelaide,Cattoli, Giovanni,Terregino, Calogero,Capua, Ilaria,Beneduce, Luca,Gallotta, Andrea,Pengo, Paolo,Fassina, Giorgio,Miertus, Stanislav,De-Eknamkul, Wanchai
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supporting information; experimental part
p. 2152 - 2157
(2012/05/05)
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- EPOXIDE INTERMEDIATE IN THE TAMIFLU SYNTHESIS
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The present invention relates to technology for preparing derivatives of unsaturated, cyclic, organic acids and salts, thereof. Shikimic acid is an example of such an acid. More particularly, the present invention relates to preparing derivatives of these acids or salts thereof that are esterified, ketalized, functionalized with a leaving group, and/or provided with epoxide functionality. Preferred aspects may be used in the synthesis of Oseltamivir Phosphate starting from shikimic acid.
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Page/Page column 18; 23
(2008/06/13)
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- Industrial synthesis of the key precursor in the synthesis of the anti-influenza drug oseltamivir phosphate (Ro 64-0796/002, GS-4104-02): Ethyl (3R,4S,5S)-4,5-epoxy-3-(1-ethyl-propoxy)-cyclohex-1 -ene-1 -carboxylate
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Starting from (-)-quinic acid, the title compound was synthesized in seven chemical steps and an overall yield of 35-38%. The route of the improved Gilead synthesis was not changed. However, significant improvements in each step led to a doubled overall yield, a 30% reduction in the number of unit operations, and an excellent quality (≥99%) of the resulting epoxide. A highly regioselective method for the dehydration of a quinic acid to a shikimic acid derivative and for the reduction of a cyclic ketal was found. Alternatively, the title compound was synthesized in six chemical steps and 63-65% yield from commercially available (-)-shikimic acid. Compared to the optimized quinic acid route, the production time was reduced by about 50%. The quality of epoxide produced from either natural product was equivalent. Therefore (-)-shikimic acid is the preferred raw material. The absolute configuration of the epoxide was determined by X-ray single crystal structure analysis and it was demonstrated that the epoxide was stereo-isomerically pure.
- Federspiel, Muriel,Fischer, Rolf,Hennig, Michael,Mair, Hans-Jürgen,Oberhauser, Thomas,Rimmler, G?sta,Albiez, Thomas,Bruhin, Jürg,Estermann, Heinrich,Gandert, Carsten,G?ckel, Volker,G?tz?, Stephan,Hoffmann, Ursula,Huber, Gabriel,Janatsch, Günter,Lauper, Stephan,R?ckel-St?bler, Odette,Trussardi, Rene,Zwahlen, Andreas G.
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p. 266 - 274
(2013/09/08)
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