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    Tetrazoleacetic acid derivatives having aldose reductase inhibitory activity
    1.
    再颁专利
    Tetrazoleacetic acid derivatives having aldose reductase inhibitory activity 失效
    具有醛糖还原酶抑制活性的四唑乙酸衍生物

    公开(公告)号：USRE35321E

    公开(公告)日：1996-08-27

    申请号：US951720

    申请日：1992-09-25

    申请人： Sinji Inukai ,  Mitsuzi Agata ,  Manami Umezawa ,  Yoshihiro Horio ,  Yasuhiro Ootake ,  Shohei Sawaki ,  Masayoshi Goto

    发明人： Sinji Inukai ,  Mitsuzi Agata ,  Manami Umezawa ,  Yoshihiro Horio ,  Yasuhiro Ootake ,  Shohei Sawaki ,  Masayoshi Goto

    IPC分类号： A61K31/41 ,  A61P3/08 ,  A61P3/10 ,  A61P13/02 ,  A61P15/00 ,  A61P25/02 ,  A61P27/02 ,  A61P27/12 ,  C07D257/04 ,  C07D405/04 ,  C07D409/04

    CPC分类号： C07D405/04 ,  C07D409/04

    摘要： A tetrazoleacetic acid derivative represented by the following general formula (I): ##STR1## .[.[in Formula (I),.]. .Iadd.wherein .Iaddend.R.sub.1 represents a hydrogen atom or an alkyl group; R.sub.2 represents a hydrogen atom, an alkyl group, an aralkyl group, a halogen atom, a haloalkyl group, a hydroxyl group, an alkoxy group, an alkoxyalkyl group, an amino group, an aryl group, an alkyl or aryl thio group, an alkyl or aryl carbonylamino group, an alkyl or aryl sulfonylamino group, an alkyl or aryl aminosulfonyl group, an alkyl or aryl sulfonyl group or an alkyl or aryl sulfinyl group; and X represents --O-- or --S--.[.].]. except for [5-(2-thienyl)tetrazol-1-yl] acetic acid, [5-(2-furyl)tetrazol-1-yl) acetic acid.Iadd., (5-(5-bromo-2-furyl)tetrazol-1-yl)acetic acid, (5-(5-phenylthio-2-furyl)tetrazol-1-yl)acetic acid, (5-(5-phenylsulfonyl-2-furyl)tetrazol-1-yl)acetic acid .Iaddend.and ethyl esters thereof, or a salt thereof shows excellent aldose reductase inhibitory activity, has low toxicity to organisms and is quite effective as an essential component of a preventative medicine and/or remedy for diabetic complications.

    摘要翻译： 由下列通式（I）表示的四唑乙酸衍生物：其中R1表示氢原子或烷基;（I） R 2表示氢原子，烷基，芳烷基，卤素原子，卤代烷基，羟基，烷氧基，烷氧基烷基，氨基，芳基，烷基或芳基硫基， 烷基或芳基羰基氨基，烷基或芳基磺酰基氨基，烷基或芳基氨基磺酰基，烷基或芳基磺酰基或烷基或芳基亚磺酰基; 和[5-（2-噻吩基）四唑-1-基]乙酸，[5-（2-呋喃基）四唑-1-基）乙酸]（其中X表示-O-或-S- [ （5-（5-溴-2-呋喃基）四唑-1-基）乙酸，（5-（5-苯基硫代-2-呋喃基）四唑-1-基）乙酸（5-（5-苯基磺酰基-2 - 呋喃基）四唑-1-基）乙酸及其乙酯或其盐显示出优异的醛糖还原酶抑制活性，对生物体具有低毒性，并且作为预防药物和/或糖尿病治疗的必需成分是非常有效的 并发症。

    Tetrazole derivatives and aldose reductase inhibition therewith
    3.
    再颁专利
    Tetrazole derivatives and aldose reductase inhibition therewith 失效
    四氮唑衍生物和醛糖还原酶抑制

    公开(公告)号：USRE35281E

    公开(公告)日：1996-06-18

    申请号：US178666

    申请日：1994-01-07

    申请人： Sinji Inukai ,  Mitsuzi Agata ,  Kiyoshi Akiba ,  Takeo Ohmura ,  Yoshihiro Horio ,  Yasuhiro Ootake ,  Shohei Sawaki ,  Masayoshi Goto

    发明人： Sinji Inukai ,  Mitsuzi Agata ,  Kiyoshi Akiba ,  Takeo Ohmura ,  Yoshihiro Horio ,  Yasuhiro Ootake ,  Shohei Sawaki ,  Masayoshi Goto

    IPC分类号： C07D257/04 ,  A61K31/41

    CPC分类号： C07D257/04

    摘要： The present invention relates to an aldose reductase inhibitor having the following formula: ##STR1## R.sub.1 is a hydrogen atom or --A--COOR.sub.5 (A is an alkylene group having 1 to 4 carbon atoms and R.sub.5 is a hydrogen atom or a lower alkyl group), and R.sub.2, R.sub.3 and R.sub.4 are the same as or different from each other and selected from the group consisting of a hydrogen atom, a hydroxy group, a halogen atom, a carboxyl group, an alkyl group, an amide group, an amino group, an alkoxy group, an aryl group, an aryloxy group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group, a nitro group, --NHCOCOOR.sub.6 (R.sub.6 is a hydrogen atom or a lower alkyl group), a mono- or dialkylaminosulfonyl group, and a residual group having the following formula: ##STR2## (A and R.sub.5 are the same as in the above). The compounds defined in the above are excellent in aldose reductase inhibitory activity and low in toxicity. Therefore, those compounds are useful as a preventive agent and/or a remedy for diabetic complications such as neuropathy, retinopathy, nephropathy, cataracts and keratopathy.

    摘要翻译： 本发明涉及具有下式的醛糖还原酶抑制剂：其中R 1为氢原子或-A-COOR 5（A为碳原子数为1〜4的亚烷基，R 5为氢原子或低级烷基 ），R2，R3和R4彼此相同或不同，并且选自氢原子，羟基，卤素原子，羧基，烷基，酰胺基，氨基 基团，烷氧基，芳基，芳氧基，烷硫基，烷基亚磺酰基，烷基磺酰基，硝基，-NHCOCOOR6（R6是氢原子或低级烷基），单或二烷基氨基磺酰基 基团和具有下式的残基：（A和R5与上述相同）。 上述定义的化合物具有优异的醛糖还原酶抑制活性和低毒性。 因此，这些化合物可用作糖尿病并发症如神经病，视网膜病，肾病，白内障和角膜病的预防剂和/或补救剂。

    Tetrazole derivatives and aldose reductase inhibition therewith
    4.
    发明授权
    Tetrazole derivatives and aldose reductase inhibition therewith 失效
    四唑衍生物和降糖抑制剂

    公开(公告)号：US5055481A

    公开(公告)日：1991-10-08

    申请号：US497500

    申请日：1990-03-22

    申请人： Sinji Inukai ,  Mitsuzi Agata ,  Kiyoshi Akiba ,  Takeo Ohmura ,  Yoshihiro Horio ,  Yasuhiro Ootake ,  Shohei Sawaki ,  Masayoshi Goto

    发明人： Sinji Inukai ,  Mitsuzi Agata ,  Kiyoshi Akiba ,  Takeo Ohmura ,  Yoshihiro Horio ,  Yasuhiro Ootake ,  Shohei Sawaki ,  Masayoshi Goto

    IPC分类号： C07D257/04

    CPC分类号： C07D257/04

    摘要： The present invention relates to an aldose reductase inhibitor having the following formula: ##STR1## R.sub.1 is a hydrogen atom or --A--COOR.sub.5 (A is an alkylene group having 1 to 4 carbon atoms and R.sub.5 is a hydrogen atom or a lower alkyl group), and R.sub.2, R.sub.3 and R.sub.4 are the same as or different from each other and selected from the group consisting of a hydrogen atom, a hydroxy group, a halogen atom, a carboxyl group, an alkyl group, an amide group, an amino group, an alkoxy group, an aryl group, an aryloxy group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group, a nitro group, --NHCOCOOR.sub.6 (R.sub.6 is a hydrogen atom or a lower alkyl group), a mono- or dialkylaminosulfonyl group, and a residual group having the following formula: ##STR2## (A and R.sub.5 are the same as in the above). The compounds defined in the above are excellent in aldose reductase inhibitory activity and low in toxicity. Therefore, those compounds are useful as a preventive agent and/or a remedy for diabetic complications such as neuropathy, retinopathy, nephropathy, cataracts and keratopathy.