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    HYDROPHILIC POLYMER DERIVATIVE HAVING CYCLIC BENZYLIDENE ACETAL LINKER
    4.
    发明公开
    HYDROPHILIC POLYMER DERIVATIVE HAVING CYCLIC BENZYLIDENE ACETAL LINKER 审中-公开
    盐酸聚合物麻醉剂环磷酰胆碱乙酰胆碱酯酶

    公开(公告)号：EP3130587A1

    公开(公告)日：2017-02-15

    申请号：EP15772451.9

    申请日：2015-03-30

    申请人： NOF Corporation

    发明人： TSUBUSAKI, Takuma ,  YAMAMOTO, Yuji

    IPC分类号： C07D317/18 ,  C07D405/06 ,  C08G65/329

    CPC分类号： C08G65/33396 ,  C07D317/20 ,  C07D317/22 ,  C07D317/24 ,  C07D317/28 ,  C07D405/06 ,  C08G65/329 ,  C08G65/3317 ,  C08G65/333 ,  C08G65/33324 ,  C08G65/33337 ,  C08G65/33341 ,  C08G65/3346 ,  C08G65/337

    摘要： To provide a hydrophilic polymer derivative having an acetal linker whose hydrolysis rate at pH of a weakly acidic environment in the living body can be accurately controlled, and which does not liberate a low molecular weight substance other than the hydrophilic polymer chain and the drug or the like connected, more specifically, a low molecular weight aldehyde, at the time of hydrolysis. The present invention relates to a hydrophilic polymer derivative having a cyclic benzylidene acetal linker represented by the following formula (1):

    wherein R 1 and R 6 are each independently a hydrogen atom or a hydrocarbon group; R 2 , R 3 , R 4 and R 5 are each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom; X 1 is a chemically reactive functional group; P is a hydrophilic polymer; s is 1 or 2, t is 0 or 1, and s + t is 1 or 2; w is an integer of 1 to 8; and Z 1 and Z 2 are each independently a selected divalent spacer.

    摘要翻译： 为了提供具有缩醛接头的亲水性聚合物衍生物，其能够精确地控制生物体中弱酸性环境的pH的水解速率，并且不释放除了亲水性聚合物链和药物之外的低分子量物质 更具体地说是低分子量的醛。 本发明涉及具有由下式（1）表示的环状亚苄基缩醛连接体的亲水性聚合物衍生物：其中R 1和R 6各自独立地为氢原子或烃基; R 2，R 3，R 4和R 5各自独立地是吸电子或给电子取代基或氢原子; X 1是化学反应性官能团; P是亲水性聚合物; s为1或2，t为0或1，s + t为1或2; w为1〜8的整数， Z 1和Z 2各自独立地为选定的二价间隔基。

    METHOD FOR PRODUCING POLYOXYETHYLENE DERIVATIVE HAVING HYDROXY GROUPS AT TERMINAL
    7.
    发明公开
    METHOD FOR PRODUCING POLYOXYETHYLENE DERIVATIVE HAVING HYDROXY GROUPS AT TERMINAL 审中-公开

    公开(公告)号：EP3604383A1

    公开(公告)日：2020-02-05

    申请号：EP18774311.7

    申请日：2018-03-22

    申请人： NOF Corporation

    发明人： YOSHIOKA, Hiroki ,  YAMAMOTO, Yuji

    IPC分类号： C08G65/32 ,  A61K47/60 ,  C08G65/28

    摘要： Provided is a method for industrially producing a polyoxyethylene derivative (1) having a plurality of hydroxy groups at a terminal. The method, which is for producing a polyoxyethylene derivative represented by formula (1), comprises steps (A), (B), (C), and (D): step (A) in which a polyhydric alcohol having five or seven hydroxy groups is subjected to a hydroxy-protecting reaction to protect four or six of the hydroxy groups by forming a cyclic benzylidene acetal, thereby obtaining a compound that has a hydroxy group at the 1-position and has a protective group having a cyclic benzylidene acetal structure; step (B) in which ethylene oxide is polymerized with the compound obtained in step (A), in an amount of 11 to 3,650 mol to obtain a polyoxyethylene derivative; step (C) in which the terminal hydroxy group of the polyoxyethylene derivative obtained in step (B) is converted to a functional group reactive with a physiologically active substance; and step (D) in which the protective group of the polyoxyethylene derivative is removed. (In formula (1), L 1 is a divalent linker; X is a functional group reactive with a physiologically active substance; a is 1 or 2; and n is 11-3,650.)