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    Modified human G-CSF
    2.
    发明公开
    Modified human G-CSF 失效
    改良人类G-CSF

    公开(公告)号：EP0335423A3

    公开(公告)日：1991-07-03

    申请号：EP89105728.3

    申请日：1989-03-31

    申请人： KYOWA HAKKO KOGYO CO., LTD.

    发明人： Yamasaki, Motoo ,  Yokoo, Yoshiharu ,  Morimoto, Makoto ,  Okabe, Masami

    IPC分类号： C07K1/107 ,  C07K14/535 ,  C07D251/26

    CPC分类号： C07K16/243 ,  A61K38/00 ,  C07K1/113 ,  C07K14/535 ,  C07K17/06

    摘要： A modified polypeptide having human granulocyte colony stimulating factor (hG-CSF) activity comprising a polypeptide having hG-CSF activity with at least one amino group thereof substituted with a group of the formula
    wherein R 1 is an alkyl or alkanoyl group; n is an optionally variable positive integer; X is 0, NH or S; R 2 is
    [where R 3 is OH, Cl, O-(CH 2 CH 2 O) n -R 1 , where R 1 and n are as defined above, Y may not be present or represents Z-(CH 2 )pCO, where Z is 0, S or NH and p is an optionally variable positive interger], or (CO) m -(CH 2 )gCO, where m is 0 or 1; t is an optionally variable positive integer, which can provide an enhanced peripheral leukocyte (granulocyte) increasing effect with improved stability and residence time in the blood and, as such, can be used advantageously in clinical medicines.

    Indolocarbazole derivatives and their use in the treatment of thrombocytopenia
    4.
    发明公开
    Indolocarbazole derivatives and their use in the treatment of thrombocytopenia 失效
    Indolocarbazol-Derivate und ihre Verwendung bei der Behandlung von Thrombozytopenie。

    公开(公告)号：EP0672668A1

    公开(公告)日：1995-09-20

    申请号：EP95103952.8

    申请日：1995-03-17

    申请人： KYOWA HAKKO KOGYO CO., LTD.

    发明人： Murakata, Chikara ,  Watanabe, Junichi ,  Saitoh, Yutaka ,  Shiotsu, Yukimasa ,  Shiraki, Takako ,  Kanai, Fumihiko ,  Tamaoki, Tatsuya ,  Akinaga, Shiro ,  Okabe, Masami

    IPC分类号： C07D498/22 ,  A61K31/55 ,  C07H19/044 ,  C07H9/06

    CPC分类号： C07D498/22 ,  C07H9/06

    摘要： Disclosed is an indolocarbazole derivative represented by the following formula (I), or a pharmaceutically acceptable salt thereof:

    [wherein R¹ represents substituted or unsubstituted lower alkyl, R² represents hydrogen, substituted or unsubstituted lower alkyl, R³ and R⁴ are the same or different, and represent hydrogen, nitro, NR⁵R⁶, OR 9, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, or CH=NNR¹⁰R¹¹, W represents two hydrogen atoms or oxygen, and Me represents methyl, provided that when R¹ is unsubstituted lower alkyl, R³ and R⁴ are not simultaneously hydrogen.

    摘要翻译： 公开了由下式（I）表示的吲哚咔唑衍生物或其药学上可接受的盐：其中R 1表示取代或未取代的低级烷基，R 2表示氢，取代或未取代的低级烷基， R 3和R 4相同或不同，表示氢，硝基，NR 5 R 6，OR 9取代或未取代的低级烷基，取代或未取代的低级链烯基或CH = NNR 1 R 1 R 1，W表示2个氢原子或氧，Me表示甲基，条件是当R 1为未被取代的低级烷基时，R 3和R 4为 不是同时氢。

    Process for producing staurosporine derivatives
    5.
    发明公开
    Process for producing staurosporine derivatives 失效
    Verfahren zur Herstellung von Staurosporin-Derivaten。

    公开(公告)号：EP0575955A1

    公开(公告)日：1993-12-29

    申请号：EP93109935.2

    申请日：1993-06-22

    申请人： KYOWA HAKKO KOGYO CO., LTD.

    发明人： Murakata, Chikara ,  Takiguchi, Toshimitsu ,  Katsumata, Shigeo ,  Mihara, Akira ,  Takahashi, Keiichi ,  Saito, Hiromitsu ,  Akinaga, Shiro ,  Okabe, Masami ,  Saito, Yutaka

    IPC分类号： C07D498/22 ,  A61K31/55 ,  C07H19/04

    CPC分类号： C07D498/22 ,  C07H9/06 ,  C07H19/04

    摘要： Disclosed is a process for producing a staurosporine derivative represented by Formula (I):

    wherein:
      Q   represents hydrogen or

            -X-(CH₂) m -Y-(CH₂) n -Z

    or a pharmaceutically acceptable salt thereof, which comprises oxidizing a compound represented by Formula (II)

    wherein Q has the same meaning as previously defined,with dimethylsulfoxide (DMSO) and an aqueous alkaline solution. Also, disclosed is a novel staurosporine derivative represented by the formula (I) wherein Q is


            -X-(CH₂) m -Y-(CH₂)₄-Z

    The staurosporine derivative (I) possesses selective protein kinase C-inhibitory and cell growth-inhibiting activities, and platelet-increasing activity.

    摘要翻译： 公开了一种制备由式（I）表示的星形孢菌素衍生物的方法：其中：Q表示氢或-X-（CH2）mY-（CH2）nZ或其药学上可接受的盐，其包括将代表的化合物 通过式（II）其中Q具有与上述定义相同的含义，与二甲基亚砜（DMSO）和碱性水溶液混合。 此外，公开了由式（I）表示的新颖的星形孢菌素衍生物，其中Q是-X-（CH2）mY-（CH2）4-Z星形孢菌素衍生物（I）具有选择性蛋白激酶C抑制和细胞生长抑制 活动和血小板增加活动。

    Modified human G-CSF
    7.
    发明公开
    Modified human G-CSF 失效
    Modifizierter人类G-CSF。

    公开(公告)号：EP0335423A2

    公开(公告)日：1989-10-04

    申请号：EP89105728.3

    申请日：1989-03-31

    申请人： KYOWA HAKKO KOGYO CO., LTD.

    发明人： Yamasaki, Motoo ,  Yokoo, Yoshiharu ,  Morimoto, Makoto ,  Okabe, Masami

    IPC分类号： C07K1/107 ,  C07K14/535 ,  C07D251/26

    CPC分类号： C07K16/243 ,  A61K38/00 ,  C07K1/113 ,  C07K14/535 ,  C07K17/06

    摘要： A modified polypeptide having human granulocyte colony stimulating factor (hG-CSF) activity comprising a polypeptide having hG-CSF activity with at least one amino group thereof substituted with a group of the formula
    wherein R 1 is an alkyl or alkanoyl group; n is an optionally variable positive integer; X is 0, NH or S; R 2 is
    [where R 3 is OH, Cl, O-(CH 2 CH 2 O) n -R 1 , where R 1 and n are as defined above, Y may not be present or represents Z-(CH 2 )pCO, where Z is 0, S or NH and p is an optionally variable positive interger], or (CO) m -(CH 2 )gCO, where m is 0 or 1; t is an optionally variable positive integer, which can provide an enhanced peripheral leukocyte (granulocyte) increasing effect with improved stability and residence time in the blood and, as such, can be used advantageously in clinical medicines.

    摘要翻译： 一种具有人粒细胞集落刺激因子（hG-CSF）活性的经修饰的多肽，其包含具有hG-CSF活性的多肽，其至少一个氨基被式R1〜OCH2CH2 @ nX-R2-（Ⅰ）所示基团取代，其中R1 是烷基或烷酰基; n是可选的可变正整数; X是O，NH或S; R 2是 [其中R 3是OH，Cl，O-（CH 2 CH 2 O）n -R 1，其中R 1和n如上所定义，Y可以不存在或表示Z-（CH 2）p CO，其中Z是O， S或NH，p是任选可变的正整数]或（CO）m-（CH 2）l CO，其中m是0或1; l是任选可变的正整数，其可以提供增强的外周白细胞（粒细胞）增加效果，并且在血液中具有改善的稳定性和停留时间，因此可以有利地用于临床药物。

    Novel polypeptide
    8.
    发明公开
    Novel polypeptide 失效
    Neues Polypeptid。

    公开(公告)号：EP0272703A1

    公开(公告)日：1988-06-29

    申请号：EP87119157.3

    申请日：1987-12-23

    申请人： KYOWA HAKKO KOGYO CO., LTD.

    发明人： Kuga, Tetsuro ,  Komatsu, Yoshinori ,  Miyaji, Horomasa ,  Sato, Moriyuki ,  Okabe, Masami ,  Morimoto, Makoto ,  Itoh, Seiga ,  Yamasaki, Motoo ,  Yokoo, Yoshiharu ,  Yamaguchi, Kazuo

    IPC分类号： C12N15/70 ,  C07K15/00 ,  C12P21/00

    CPC分类号： C07K16/243 ,  A61K38/00 ,  C07K14/535 ,  C12N15/70

    摘要： Novel hG-CSF polypeptide derivatives having an amino acid sequence derived from the amino acid sequence of the human granulocyte colony stimulating factor polypeptide by substitution of at least one amino acid by a different aminoacid and/or deletion of at least one amino acid, recombinant plasmids containing a DNA fragment insert coding for any of these hG-CSF polypeptide derivatives, microorganisms carrying one of such plasmids, and methods of producing the hG-CSF polypeptide derivatives using the microorganisms are described.

    摘要翻译： 具有衍生自人粒细胞集落刺激因子多肽的氨基酸序列的氨基酸序列的新型hG-CSF多肽衍生物通过用至少一个氨基酸的不同氨基酸和/或缺失取代至少一个氨基酸的重组质粒 含有编码这些hG-CSF多肽衍生物中的任何一个的DNA片段插入片段，携带这种质粒之一的微生物，以及使用微生物产生hG-CSF多肽衍生物的方法。