Wakamoto Pharmaceutical Co., Ltd.

Yasuhiro Ootake

Shohei Sawaki

Yoshihiro Horio

Masayoshi Goto

Sinji Inukai

Mitsuzi Agata

Kiyoshi Akiba

Manami Umezawa

Takeo Ohmura

Mitsuji Agata

Terumasa Hashimoto

Tooru Abe

A tetrazoleacetic acid derivative represented by the following general formula I: ##STR1## wherein in the formula I, R represents a hydrogen atom or a lower alkyl group; A is an alkylene group having 2 to 5 carbon atoms; Ar is selected from the group consisting of a phenyl group, a naphthyl group, a furyl group, a thienyl group, a benzofuryl group, and a benzothienyl group; wherein the Ar may be substituted with a lower alkyl group, a lower alkoxy group, a halogen atom, a lower haloalkyl group, an alkylthio group and an alkylsulfonylamino group shows excellent aldose reductase inhibitory activity, and is quite effective as an essential component of a preventive medicine and/or remedy for diabetic complications.

Tetrazoleacetic acid derivatives and method of aldose reductase

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.

Tetrazoleacetic acid derivatives having aldose reductase inhibitory

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.

Tetrazoleacetic acid derivatives and use for aldose reductase inhibitory

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.

Tetrazole derivatives and aldose reductase inhibition therewith

A new compound, 3-(1H-tetrazol-5-yl)oxanilic acid and pharmaceutically acceptable salts thereof are herein disclosed, which can be prepared by reacting 3-(1H-tetrazol-5-yl)aniline with a compound represented by the general formula: A--CO--CO--B (wherein A and B may be identical with or different from one another and represent hydroxyl group, a halogen atom or a lower alkoxy group) and then optionally hydrolyzing the resultant product. The compound presents an excellent histamine and SRS-A release inhibitory effect and is hydrophilic or soluble in water. Therefore, the compound is very suitable to form, in particular, an aqueous pharmaceuticals for treatment or prevention of allergic diseases such as bronchial asthma, rhinitis and conjunctivitis.

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Minami-ashigara, Japan

Yasuhiro Ootake