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    Sulfonylamino acid derivatives as metalloproteinase inhibitors
    7.
    发明公开
    Sulfonylamino acid derivatives as metalloproteinase inhibitors 失效
    磺酰氨基酸衍生物作为金属蛋白酶抑制剂

    公开(公告)号：EP0757037A3

    公开(公告)日：1999-12-22

    申请号：EP96305554.6

    申请日：1996-07-29

    申请人： ONO PHARMACEUTICAL CO., LTD.

    发明人： Sakaki, Katsuhito, Ono Pharmaceutical Co., Ltd. ,  Kanazawa, Hidekazu, Ono Pharmaceutical Co., Ltd. ,  Sugiura, Tsuneyuki, Ono Pharmaceutical Co., Ltd. ,  Miyazaki, Tohru, Ono Pharmaceutical Co., Ltd. ,  Ohno, Hyroyuki, Ono Pharmaceutical Co., Ltd.

    IPC分类号： C07C311/42 ,  A61K31/63 ,  C07D209/20 ,  C07D213/59 ,  C07D233/64 ,  C07D333/24 ,  C07D213/82 ,  C07D307/68

    CPC分类号： C07D213/81 ,  C07C311/19 ,  C07C311/29 ,  C07C311/46 ,  C07C311/47 ,  C07D209/20 ,  C07D213/55 ,  C07D233/64 ,  C07D307/71 ,  C07D333/38

    摘要： The present invention relates to:
    (i) matrix metalloproteinase (MMP) inhibitors containing sulfonylamino acid derivatives of the formula (Ia):
    wherein R 1 is hydrogen, C1-4 alkyl; R 2 is hydrogen, C1-8 alkyl etc.; E is -CONR 3 -, in which R 3 is hydrogen, C1-4 alkyl etc., -NR 3 CO-, -CO-O-, -O-CO- etc.; A is hydrogen, C1-8 alkyl, C3-7 cycloalkyl, or Ar; J is bond, C2-4 alkylene etc.; G is -(CH 2 ) m -, in which m is 2, 3 or 4, or
    in which R 6 and R 7 is hydrogen, C1-8 alkyl etc.; and non-toxic salts thereof, (ii) novel sulfonylamino acid derivatives of the formula (Ib):
    wherein all the symbols are as defined for formula (Ia), with the exclusion of certain compounds; and non-toxic salts thereof, and (iii) processes for the preparation of the compounds of formula (Ib). The compounds of formulae (Ia) and (Ib) are useful for prevention and/or treatment of diseases induced by overexpression or excess activity of MMP, such as rheumatoid diseases, arthrosteitis, unusual bone resorption, osteoporosis, periodontitis, interstitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, metastasis, invasion or growth of tumor cells, autoimmune diseases (Crohn's disease, Sjogren's syndrome etc.), diseases caused by vascular emigration or infiltration of leukocytes, or arterialization.

    摘要翻译： 本发明涉及：（i）含有式（Ia）的磺酰氨基酸衍生物的基质金属蛋白酶（MMP）抑制剂：其中R 1为氢，C 1-4烷基; R2是氢，C1-8烷基等; E是-CONR3-，其中R3是氢，C1-4烷基等，-NR3CO-，-CO-O - ， - O-CO-等; A是氢，C 1-8烷基，C 3-7环烷基或Ar; J是键，C2-4亚烷基等; G是 - （CH2）m-，其中m是2,3或4，或其中R6和R7是氢，C1-8烷基等。 （ii）式（Ib）的新型磺酰氨基酸衍生物：其中所有符号如式（Ia）中所定义，但排除某些化合物; 和其无毒盐，和（iii）制备式（Ib）化合物的方法。 式（Ia）和（Ib）的化合物可用于预防和/或治疗由MMP的过表达或过量活性诱导的疾病，例如类风湿性疾病，关节炎，异常骨吸收，骨质疏松症，牙周炎，间质性肾炎，动脉硬化， 肺气肿，肝硬化，角膜损伤，转移，肿瘤细胞侵袭或生长，自身免疫性疾病（克罗恩氏病，舍格伦氏综合征等），由血管移植或白细胞浸润引起的疾病或动脉化。