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    Nitration process
    11.
    发明专利
    Nitration process 失效
    硝化过程

    公开(公告)号：JPS6115847A

    公开(公告)日：1986-01-23

    申请号：JP13655784

    申请日：1984-07-03

    Applicant: Kowa Co

    Inventor： KAWAMURA KIYOSHI ,  SHIBUYA MASAYUKI ,  ISHIHAMA HIROSHI

    IPC: C07D311/64 ,  C07B31/00 ,  C07B43/00 ,  C07C67/00 ,  C07C201/00 ,  C07C201/02 ,  C07C203/02 ,  C07C239/00 ,  C07C301/00 ,  C07C303/28 ,  C07C303/32 ,  C07C305/00 ,  C07D209/12 ,  C07D211/90 ,  C07D213/30 ,  C07D213/80 ,  C07D221/00 ,  C07D317/00 ,  C07D491/056

    Abstract: PURPOSE:To produce a nitric acid ester, in high yield and purity, economically in an industrial scale, easily under mild condition, using a regenerable reagent, by reacting a sulfonic acid ester with an organic quaternary ammonium nitrate. CONSTITUTION:The objective compound of formula III can be produced by reacting (A) the sulfonic acid ester of formula II (R'SO2 is sulfonic acid residue) obtained by the conventional sulfonation process of an alcohol of formula I (R is organic residue) with (B) the organic quaternary ammonium nitrate of formula IV(Q is organic quaternary ammonium residue), e.g. a quaternary alkyl (or substituted alkyl) ammonium nitrate or a nitrate of a strongly basic anion exchange resin having quaternary ammonium as an exchangeable group. The process can be applied to a compound which is difficult to be nitrated by conventional methods. When the process is applied to an optically active compound, a nitrate having inverted absolute configuration is prepared without causing racemization.

    Abstract translation: 目的：通过使磺酸酯与有机季硝酸铵反应，以高产率和纯度生产硝酸酯，在工业规模上经济地容易地在温和条件下使用可再生试剂。 结构式：式Ⅲ的目的化合物可以通过使（A）式Ⅱ的磺酸酯（R'SO 2是磺酸残基）与通式Ⅰ的醇（R是有机残基）的常规磺化方法得到的 与（B）式IV的有机季铵硝酸盐（Q +是有机季铵残基），例如 具有季铵作为可交换基团的强碱性阴离子交换树脂的季烷基（或取代的烷基）硝酸铵或硝酸盐。 该方法可以应用于难以用常规方法硝化的化合物。 当将该方法应用于光学活性化合物时，制备具有反向绝对构型的硝酸盐而不引起外消旋化。

    Therapeutic and/or prophylactic agent for fatty liver disorder
    12.
    发明专利
    Therapeutic and/or prophylactic agent for fatty liver disorder 审中-公开
    用于脂肪肝病的治疗和/或预防剂

    公开(公告)号：JP2013199435A

    公开(公告)日：2013-10-03

    申请号：JP2012066796

    申请日：2012-03-23

    Applicant: Kowa Co ,  興和株式会社

    Inventor： MURAKAMI TAKESHI ,  MURAKAMI KENTARO ,  OGIYA TADAAKI ,  SHIBUYA MASAYUKI

    IPC: A61K31/421 ,  A61K31/505 ,  A61P1/16 ,  A61P43/00

    Abstract: PROBLEM TO BE SOLVED: To provide a therapeutic and/or prophylactic agent for fatty liver disorder.SOLUTION: A therapeutic and/or prophylactic agent for fatty liver disorder includes a compound having cholesterol ester transfer protein inhibiting activity or its salt or their solvate as an active ingredient.

    Abstract translation: 要解决的问题：提供用于脂肪肝疾病的治疗和/或预防剂。解决方案：用于脂肪肝疾病的治疗和/或预防剂包括具有胆固醇酯转运蛋白抑制活性的化合物或其盐或其溶剂合物作为 有效成分。

    Method for producing optically-active 1-[3,5-bis(trifluoromethyl)phenyl]ethane derivative
    13.
    发明专利
    Method for producing optically-active 1-[3,5-bis(trifluoromethyl)phenyl]ethane derivative 审中-公开
    生产光活性1- [3,5-二（三氟甲基）苯基]乙烯衍生物的方法

    公开(公告)号：JP2013136573A

    公开(公告)日：2013-07-11

    申请号：JP2012263934

    申请日：2012-12-03

    Applicant: Kowa Co ,  興和株式会社

    Inventor： YAMAZAKI KOICHI ,  MATSUDA KENNOSUKE ,  KUSAKABE TAICHI ,  OGIYA TADAAKI ,  SHIBUYA MASAYUKI

    IPC: C07D239/47 ,  A61K31/505 ,  A61P3/06 ,  A61P43/00 ,  C07B55/00 ,  C07B57/00

    Abstract: PROBLEM TO BE SOLVED: To provide a method for efficiently producing optically-active 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane in a high yield from otpically-active 1-[3,5-bis(trifluoromethyl)phenyl]ethanol while maintaining high optical purity, and further producing an otpically-active material of [3,5-bis(trifluoromethyl)phenyl]ethane derivative.SOLUTION: The method for producing an optically-active material of 1-[3,5-bis(trifluoromethyl)phenyl]ethane derivative includes the step of obtaining optically-active 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane by brominating optically-active 1-[3,5-bis(trifluoromethyl)phenyl]ethanol by use of, as a brominating agent, (a) a combination of phosphor halide and hydrogen bromide; (b) a combination of 1,2-dibromo-1,1,2,2-tetrachloroethane and an organic phosphor compound represented by general formula (4) P(R)(R)(R) (R, Rand Reach represent 6-10C aryl); or (c) a combination of N-bromosuccinimide and dialkyl sulfide.

    Abstract translation: 要解决的问题：提供从高效1-（3,5-双（三氟甲基）苯基]乙烷的高收率产生光学活性的1-溴-1- [3,5-双（三氟甲基）苯基]乙烷的方法， 三氟甲基）苯基]乙醇，同时保持高的光学纯度，并进一步制备[3,5-双（三氟甲基）苯基]乙烷衍生物的活性物质。溶液：1- [3 ，5-双（三氟甲基）苯基]乙烷衍生物包括通过溴化光学活性的1- [3,5-双（三氟甲基）苯基]乙烷的光学活性1- [ （三氟甲基）苯基]乙醇作为溴化剂，（a）卤化磷和溴化氢的组合; （b）1,2-二溴-1,1,2,2-四氯乙烷与由通式（4）表示的有机荧光体化合物的组合（R）（R）（R）（R，兰德·达奇代表6 -10C芳基）; 或（c）N-溴代琥珀酰亚胺和二烷基硫醚的组合。

    Highly pure deuterated derivative and its production method
    14.
    发明专利
    Highly pure deuterated derivative and its production method 审中-公开
    高纯度衍生衍生物及其生产方法

    公开(公告)号：JP2010006767A

    公开(公告)日：2010-01-14

    申请号：JP2008169532

    申请日：2008-06-27

    Applicant: Kowa Co ,  興和株式会社

    Inventor： YAMAZAKI YUKIYOSHI ,  OGAWA SHINICHIRO ,  SHIBUYA MASAYUKI

    IPC: C07D263/58 ,  C07B59/00 ,  C07B61/00 ,  C07C217/20 ,  C07C255/13

    Abstract: PROBLEM TO BE SOLVED: To provide a standard substance for measurement that can be perfectly separated from (R)-2-[3-[N-(benzoxazol-2-yl)-N-[3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid to permit accurate and efficient measurement in the LC/MS/MS method, and to provide its production method. SOLUTION: Deuterated (R)-2-[3-[N-(benzoxazol-d 4 -2-yl)-N-[3-(4-methoxyphenoxy-d 7 )propyl]aminomethyl]phenoxy] butyric acid is useful as a standard substance in mass spectrometric analysis. A manufacturing method of the derivative is also provided. COPYRIGHT: (C)2010,JPO&INPIT

    Abstract translation: 要解决的问题：提供可以从（R）-2- [3- [N-（苯并恶唑-2-基）-N- [3-（4-甲氧基苯氧基） ）丙基]氨基甲基]苯氧基]丁酸，以在LC / MS / MS方法中进行准确和有效的测量，并提供其制备方法。 氘代（R）-2- [3- [N-（苯并恶唑-d 4 SB 2 -2-基）-N- [3-（4-甲氧基苯氧基-d SB） 7]丙基]氨基甲基]苯氧基]丁酸在质谱分析中可用作标准物质。 还提供了衍生物的制造方法。 版权所有（C）2010，JPO＆INPIT

    Novel amide structure-having pyrimidine compound and medicine containing the same
    15.
    发明专利
    Novel amide structure-having pyrimidine compound and medicine containing the same 审中-公开
    具有新型酰胺结构的吡咯胺化合物和含有它的药物

    公开(公告)号：JP2008127393A

    公开(公告)日：2008-06-05

    申请号：JP2007301163

    申请日：2007-11-21

    Applicant: Kowa Co ,  興和株式会社

    Inventor： OGIYA TADAAKI ,  MIURA TORU ,  OKUDA AYUMI ,  ARAI TOSHIHARU ,  YAMAZAKI KOICHI ,  AOKI TARO ,  MIYOSAWA KATSUTOSHI ,  SHIBATA HARUKI ,  SHIBUYA MASAYUKI

    IPC: C07D239/47 ,  A61K31/505 ,  A61K31/506 ,  A61P3/06 ,  A61P9/00 ,  A61P9/10 ,  A61P9/12 ,  C07D401/12

    Abstract: PROBLEM TO BE SOLVED: To provide a compound that shows strong inhibitory action against cholesterol ester transferring protein (CETP), has good oral absorptivity and gives high concentration in blood. SOLUTION: The compound is represented by general formula (I) (wherein X 1 is carbonyl or sulfonyl, X 2 is N atom or C-R 12 , and R 1 , R 2 , R 3 , R 4 and R 5 are each an H atom, a halogen atom, a lower alkyl or the like, R 6 , R 7 , R 8 , and R 12 are each an H atom, a halogen atom, a lower alkyl, or the like, R 9 and R 10 are each an H atom, a lower alkyl, a lower cycloalkyl lower alkyl or the like, and R 11 is an H atom, a halogen atom, a lower alkoxy or the like). COPYRIGHT: (C)2008,JPO&INPIT

    Abstract translation: 待解决的问题：为了提供对胆固醇酯转移蛋白（CETP）具有强抑制作用的化合物，具有良好的口服吸收性并且在血液中具有高浓度。 解决方案：该化合物由通式（I）表示（其中X 1是羰基或磺酰基，X 2 是N原子或CR 12 < / SP>和R 1 ，R 2 ，R 3 ，R 4 和R 5 R 2是H原子，卤素原子，低级烷基等，R 6，R 7， R 12和R 14各自为H原子，卤素原子，低级烷基等，各自独立地为 H原子，低级烷基，低级环烷基低级烷基等，R 11是H原子，卤素原子，低级烷氧基等）。 版权所有（C）2008，JPO＆INPIT

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