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    • 2. 发明授权
    • Process for producing acyclic nucleosides and process for separating
purine nucleosides
    • 用于生产无环核苷的方法和用于分离嘌呤核苷的方法
    • US5792868A
    • 1998-08-11
    • US214756
    • 1994-03-18
    • Kunisuke IzawaYoshihito KoguchiHiroshi Shiragami
    • Kunisuke IzawaYoshihito KoguchiHiroshi Shiragami
    • C07D473/00C07D473/18C07H19/16C07D473/16C07D473/30C07D473/34
    • C07D473/00C07D473/18C07H19/16
    • Herein is disclosed a novel and industrially advantageous process for synthesizing acyclic nucleosides such as acyclovir and ganciclovir from ribonucleosides, which process comprises adding an acid catalyst and an acid anhydride to a solution of a ribonucleoside such as guanosine and an ester derivative of an acyclic sugar, and heating the mixture, whereby a transglycosilation reaction takes place between the ribose moiety of the ribonucleoside and the ester derivative of the acyclic sugar. Herein is also disclosed an industrially favorable method for the separation of 9-substituted purine nucleosides which are important intermediates for the synthesis of acyclic nucleosides such as acyclovir, ganciclovir, and the like from ribonucleosides, which method comprises crystallizing only the 9-isomer from a solution or suspension containing both a 9-substituted purine nucleoside and a 7-substituted purine nucleoside by cooling the solution or/and by adding a crystallizing solvent thereto.
    • 本文公开了一种用于从核糖核苷合成无环型核苷如阿昔洛韦和更昔洛韦的新颖且工业上有利的方法,该方法包括向核糖核苷如鸟苷和无环糖的酯衍生物的溶液中加入酸催化剂和酸酐, 并加热混合物,由此在核糖核苷的核糖部分和无环糖的酯衍生物之间发生反缩糖反应。 本文还公开了用于分离9-取代嘌呤核苷的工业上有利的方法,其是从核糖核苷合成无环核苷如阿昔洛韦,更昔洛韦等的重要中间体,该方法包括仅将9-异构体从 通过冷却溶液或/和通过向其中加入结晶溶剂而含有9-取代的嘌呤核苷和7-取代的嘌呤核苷的溶液或悬浮液。
    • 5. 发明申请
    • Nateglinide crystals
    • 那格列奈晶体
    • US20050101672A1
    • 2005-05-12
    • US10965171
    • 2004-10-15
    • Yoshihito KoguchiTomoko NakaoMichito Sumikawa
    • Yoshihito KoguchiTomoko NakaoMichito Sumikawa
    • A61K31/198C07C233/63C07C233/76
    • C07C233/63C07C2601/14
    • New nateglinide crystals, i.e. nateglinide A-type crystals (main peaks in powder X-ray diffraction: 4.4°, 5.2°, 15.7°, 18.5°(2θ)), M-type crystals (main peaks in powder X-ray diffraction: 6.0°, 14.2°, 15.2°, 18.8°(2θ)) and P-type crystals (main peaks in powder X-ray diffraction: 4.8°, 5.3°, 14.3°, 15.2°(2θ)), can be produced by dissolving nateglinide in a solvent in which nateglinide is highly soluble and then adding a solvent in which nateglinide is difficultly soluble or, alternatively, by dissolving nateglinide in a mixed solvent composed of a solvent in which nateglinide is highly soluble and another solvent in which it is difficultly soluble, cooling the nateglinide solution to form crystals, filtering the mixture and drying the crystals at a specified temperature.
    • 新那格列奈晶体,即那格列奈A型晶体(粉末X射线衍射中的主峰:4.4°,5.2°,15.7°,18.5°(2θ)),M型晶体(粉末X射线衍射中的主峰: 6.0°,14.2°,15.2°,18.8°(2θ))和P型晶体(粉末X射线衍射中的主峰:4.8°,5.3°,14.3°,15.2°(2θ))可以通过 将那格列奈溶解在那格列奈高度溶解的溶剂中,然后加入那格列奈难以溶解的溶剂,或者通过将那格列奈溶解在由那格列奈高度溶解的溶剂和其中所述的其他溶剂组成的混合溶剂中 难以溶解,冷却那格列奈溶液形成晶体,过滤混合物并在特定温度下干燥晶体。
    • 8. 发明授权
    • Nateglinide crystals
    • 那格列奈晶体
    • US07586001B2
    • 2009-09-08
    • US12098118
    • 2008-04-04
    • Yoshihito KoguchiTomoko NakaoMichito Sumikawa
    • Yoshihito KoguchiTomoko NakaoMichito Sumikawa
    • C07C229/00C07C51/15
    • C07C233/63C07C2601/14
    • New nateglinide crystals, i. e. nateglinide A-type crystals (main peaks in powder X-ray diffraction: 4.4°, 5.2°, 15.7°, 18.5° (2θ)), M-type crystals (main peaks in powder X-ray diffraction: 6.0°, 14.2°, 15.2°, 18.8° (2θ)) and P-type crystals (main peaks in powder X-ray diffraction: 4.8°, 5.3°, 14.3°, 15.2° (2θ)), can be produced by dissolving nateglinide in a solvent in which nateglinide is highly soluble and then adding a solvent in which nateglinide is difficultly soluble or, alternatively, by dissolving nateglinide in a mixed solvent composed of a solvent in which nateglinide is highly soluble and another solvent in which it is difficultly soluble, cooling the nateglinide solution to form crystals, filtering the mixture and drying the crystals at a specified temperature.
    • 新奈格列奈晶体, e。 那格列奈A型晶体(粉末X射线衍射中的主峰:4.4°,5.2°,15.7°,18.5°(2θ)),M型晶体(粉末X射线衍射中的主峰:6.0°,14.2° ,15.2°,18.8°(2θ))和P型晶体(粉末X射线衍射中的主峰:4.8°,5.3°,14.3°,15.2°(2θ))可以通过将那格列奈溶解在溶剂中 其中那格列奈高度可溶,然后加入那格列奈难以溶解的溶剂,或者通过将那格列奈溶解在由那格列奈高度溶解的溶剂和难溶于其中的溶剂组成的混合溶剂中,冷却 那格列奈溶液形成晶体,过滤混合物并在特定温度下干燥晶体。
    • 10. 发明授权
    • Nateglinide crystals
    • 那格列奈晶体
    • US07411089B2
    • 2008-08-12
    • US10965171
    • 2004-10-15
    • Yoshihito KoguchiTomoko NakaoMichito Sumikawa
    • Yoshihito KoguchiTomoko NakaoMichito Sumikawa
    • C07C229/00C07C51/15
    • C07C233/63C07C2601/14
    • New nateglinide crystals, i.e. nateglinide A-type crystals (main peaks in powder X-ray diffraction: 4.4°, 5.2°, 15.7°, 18.5°(2θ)), M-type crystals (main peaks in powder X-ray diffraction: 6.0°, 14.2°, 15.2°, 18.8°(2θ)) and P-type crystals (main peaks in powder X-ray diffraction: 4.8°, 5.3°, 14.3°, 15.2°(2θ)), can be produced by dissolving nateglinide in a solvent in which nateglinide is highly soluble and then adding a solvent in which nateglinide is difficultly soluble or, alternatively, by dissolving nateglinide in a mixed solvent composed of a solvent in which nateglinide is highly soluble and another solvent in which it is difficultly soluble, cooling the nateglinide solution to form crystals, filtering the mixture and drying the crystals at a specified temperature.
    • 新那格列奈晶体,即那格列奈A型晶体(粉末X射线衍射中的主峰:4.4°,5.2°,15.7°,18.5°(2θ)),M型晶体(粉末X射线衍射中的主峰: 6.0°,14.2°,15.2°,18.8°(2θ))和P型晶体(粉末X射线衍射中的主峰:4.8°,5.3°,14.3°,15.2°(2θ))可以通过 将那格列奈溶解在那格列奈高度溶解的溶剂中,然后加入那格列奈难以溶解的溶剂,或者通过将那格列奈溶解在由那格列奈高度溶解的溶剂和其中所述的其他溶剂组成的混合溶剂中 难以溶解,冷却那格列奈溶液形成晶体,过滤混合物并在特定温度下干燥晶体。