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。

公开(公告)号：US5068239A

公开(公告)日：1991-11-26

申请号：US588057

申请日：1990-09-24

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), 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 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 preventive medicine and/or remedy for diabetic complications.

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。

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.

公开(公告)号：US5252592A

公开(公告)日：1993-10-12

申请号：US821456

申请日：1992-01-16

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： A61K31/41 ,  A61P43/00 ,  C07D257/04

CPC分类号： C07D257/04

摘要： A tetrazoleacetic acid derivative represented by the following general formula (I): ##STR1## [in Formula (I), R.sub.1 represents a hydrogen atom or a lower alkyl group; R.sub.2, R.sub.3 and R.sub.4 are the same or different from each other and are selected from the group consisting of hydrogen, lower alkyl, halogen, lower haloalkyl, hydroxy and lower alkoxy; and tetrazol group is substituted at 1- or 2-position of naphthyl group] except for [5-(1-naphthyl)tetrazol-1-yl]acetic acid and ethyl ester thereof, or a salt thereof.

公开(公告)号：US5356916A

公开(公告)日：1994-10-18

申请号：US830298

申请日：1992-01-31

申请人： Hatsunori Toyofuku ,  Jun Matsumoto ,  Toshie Takahashi ,  Masakazu Ebie ,  Naomi Sasada ,  Mitsuzi Agata ,  Shohei Sawaki ,  Masayoshi Goto

发明人： Hatsunori Toyofuku ,  Jun Matsumoto ,  Toshie Takahashi ,  Masakazu Ebie ,  Naomi Sasada ,  Mitsuzi Agata ,  Shohei Sawaki ,  Masayoshi Goto

IPC分类号： A61K31/41 ,  A61K31/4245 ,  A61K31/44 ,  A61K31/445 ,  A61K31/495 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5377 ,  A61P25/00 ,  C07D271/06 ,  C07D413/12 ,  C07D521/00 ,  C12N9/99

CPC分类号： C07D271/06 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D413/10

摘要： A 1,2,4-oxadiazole derivative is represented by the following general formula (I): ##STR1## wherein R.sup.1 represents a lower alkyl or cycloalkyl group, a lower alkyl group substituted with a halogen atom, a lower alkylamino group or a phenyl group; R.sup.2 represents a hydrogen atom, a lower dialkylamino group, a cyclic alkylamino group, a cyclic amino group having an oxygen or nitrogen atom in the ring, a phenyl group which may be substituted with a halogen atom, a pyridyl group, an imidazolyl group, an alkylimidazolyl group, a benzimidazolyl group or a 2-oxopyrrolidinyl group; and n is 1, 2 or 3. The derivative has excellent monoamine oxidase-inhibitory activity and is effective as a medicine for treating Parkinson's disease.

摘要翻译： 1,2,4-恶二唑衍生物由以下通式（I）表示：其中R 1表示低级烷基或环烷基，被卤素原子取代的低级烷基，低级烷基氨基 或苯基; R2表示氢原子，低级二烷基氨基，环状烷基氨基，环中具有氧或氮原子的环状氨基，可被卤素原子取代的苯基，吡啶基，咪唑基， 烷基咪唑基，苯并咪唑基或2-氧代吡咯烷基; 并且n为1,2或3.该衍生物具有优异的单胺氧化酶抑制活性，作为治疗帕金森病的药物是有效的。

公开(公告)号：US20050124699A1

公开(公告)日：2005-06-09

申请号：US11025990

申请日：2005-01-03

申请人： Kiyoshi Akiba ,  Futoshi Hoshina ,  Mitsuzi Agata

发明人： Kiyoshi Akiba ,  Futoshi Hoshina ,  Mitsuzi Agata

IPC分类号： A61K9/00 ,  A61K31/196 ,  A61K31/5575 ,  A61K45/06 ,  A61K31/557

CPC分类号： A61K45/06 ,  A61K9/0048 ,  A61K31/196 ,  A61K31/5575 ,  A61K2300/00

摘要： The present invention provides an eye drop for treating or preventing disorders of corneal and/or conjunctival epithelial cells comprising prostaglandin E's as effective components; and an eye drop for treating or preventing disorders of corneal and/or conjunctival epithelial cells comprising prostaglandin E's and an anti-inflammatory agent as effective components. The eye drop shows a high effect of treating and/or preventing disorders of cornea or conjunctiva originated from physical, chemical and/or mechanical damages of the cornea or conjunctiva as well as endogenous disorders of cornea or conjunctiva.

摘要翻译： 本发明提供了用于治疗或预防包含前列腺素E作为有效成分的角膜和/或结膜上皮细胞疾病的滴眼剂; 以及用于治疗或预防包含前列腺素E和抗炎剂作为有效成分的角膜和/或结膜上皮细胞疾病的眼药水。 眼药水显示出治疗和/或预防由于角膜或结膜的物理，化学和/或机械损伤以及角膜或结膜的内源性障碍引起的角膜或结膜疾病的高效果。