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1. 发明专利

JPH1129478A PHARMACEUTICAL COMPOSITION CONTAINING DIHYDROQUINOLINE DERIVATIVE 失效
公开(公告)号：JPH1129478A
公开(公告)日：1999-02-02
申请号：JP18387097
申请日：1997-07-09
申请人： OTSUKA PHARMA FACTORY INC
发明人： SHIBUYA NAOMASA , HASHIMOTO KINJI , INOUE YASUHIDE , SATO KEIGO , MIKI SHINYA
IPC分类号： C07D215/36 , A61K31/47 , A61K31/54 , A61P3/08 , A61P3/10 , C07D409/04 , C07D411/04 , C07F9/40
摘要： PROBLEM TO BE SOLVED: To obtain a pharmaceutical composition capable of treating and preventing diabetes as a hypoglycemic agent by including a dihydroquinoline derivative as an active ingredient. SOLUTION: This composition contains a dihydroquinoline derivative of the formula (R is H or a halogen; R is H, a lower alkyl or phenyl; R is a lower alkyl, a hydroxy lower alkyl or phenyl; R is a di(lower alkyl)phosphoro(lower alkyl), a (lower alkoxycarbonyl) lower alkyl, N-(lower alkyl)carbamoyl(lower alkyl), etc.; R and R form 1,4-thioxane ring by binding with S to each other), which is a new compound. 6-Chloro-1-methyl-3-[methyl(diethylphophoromethyl)sulfonio]-2-oxo-1,2- dihydroquinolin-4-olate is exemplified as the compound of the formula. The daily dose of the pharmaceutical preparation is 0.5-20 mg/kg and administered by dividing to 1-4 times.

2. 发明专利

JPH08143586A PHOSPHONIC ACID DIESTER DERIVATIVE 失效
公开(公告)号：JPH08143586A
公开(公告)日：1996-06-04
申请号：JP3526195
申请日：1995-02-23
申请人： OTSUKA PHARMA FACTORY INC
发明人： KUROKI YASUHISA , MIYATA KAZUYOSHI , TSUDA YOSHIHIKO , INOUE YASUHIDE , KANEYA ATSUSHI , SATO KEIGO
IPC分类号： A61K31/675 , A61P3/06 , A61P3/08 , A61P3/10 , A61P9/12 , C07F9/6512
摘要： PURPOSE: To provide a new compound having excellent hypolipidemic action, hypotonic action and hypoglycenaic action and useful as an agent for the treatment of hyperlipidemia, hypertension, diabetes, etc. CONSTITUTION: This compound is expressed by formula I (R to R and R are each H, a lower alkyl, etc.; R4 is phenyl, a lower alkyl, etc.; R is a lower alkyl; R is a lower alkoxy, hydroxy, etc.; X and X are each O or S; A is O or single bond; Z is a lower alkylene), e.g. diethyl-4-(7-chloro-3-methyl-4(3H)- quinazol inon-2-yl)benzyl phosphonate. The compound can be produced e.g. by monohalogenating a 2-(toluyl)-4(3H)-quinazolinone derivative of formula II (R to R and R are each H, nitro, etc.; R is phenyl, a lower alkenyl, etc.) with a halogenation agent such as bromine in an inert solvent in the presence of a catalyst such as benzoyl peroxide and reacting the resultant benzyl halide derivative with a trialkyl phosphite of formula P(OR )3 .

3. 发明专利

JPH10167964A COUMARIN DERIVATIVE-CONTAINING MEDICINAL COMPOSITION 失效
公开(公告)号：JPH10167964A
公开(公告)日：1998-06-23
申请号：JP32550396
申请日：1996-12-05
申请人： OTSUKA PHARMA FACTORY INC
发明人： SHIBUYA NAOMASA , KAWAMURA KENICHI , HASHIMOTO KINJI , INOUE YASUHIDE , SATO KEIGO , MIKI SHINYA
IPC分类号： C07D311/56 , A61K31/35 , A61K31/352 , A61K31/38 , A61K31/385 , A61K31/40 , A61K31/4433 , A61K31/445 , A61K31/495 , A61K31/54 , A61P3/08 , A61P3/10 , C07D409/04 , C07D411/04 , C07D417/04
摘要： PROBLEM TO BE SOLVED: To obtain the subject composition that contains a novel coumarin derivative as an active ingredient and is useful for treatment or prevention of diabetes as a hypoglycemic. SOLUTION: The objective composition contains, as an active ingredient, about 1-70wt.% of a coumarin derivative of formula I (R is a hydrogen atom, an alkyl, an alkoxy; R is an alkyl, a phenylalkyl, a carboxyalkyl, an alkoxycarbonylalkyl), typically 3-[methyl(diethyl-phosphoromethyl) sulfonio]coumarin-4-olate. The coumarin derivative of formula I is prepared, for example, by allowing a compound of formula II to react with iodobenzene diacetate in the presence of an alkali, for example, sodium carbonate in a solvent (water), then allowing the resultant compound of formula III to react with a thioether derivative of the formula: R -S-R in the presence of an acidic catalyst (acetic acid) in a solvent (methanol).

4. 发明专利

JPH09124615A QUINAZOLINONE DERIVATIVE 失效
公开(公告)号：JPH09124615A
公开(公告)日：1997-05-13
申请号：JP28522795
申请日：1995-11-01
申请人： OTSUKA PHARMA FACTORY INC
发明人： KUROKI YASUHISA , KAWAMURA KENICHI , SAKAI YASUHIRO , HASHIMOTO KINJI , MIYATA KAZUYOSHI , SHIBUYA NAOMASA , INOUE YASUHIDE , SATO KEIGO , MIKI SHINYA
IPC分类号： C07D239/91 , A61K31/505 , A61K31/517 , A61P3/08 , A61P3/10 , C07D401/10 , C07D403/10 , C07D409/10 , C07D413/12 , C07D417/12
摘要： PROBLEM TO BE SOLVED: To obtain a new equinazolinone derivative as a therapeutic agent for diabetic, having hypoglycemic action. SOLUTION: A compound is shown by formula I [R is H or a halogen; R is a lower alkyl; (m) is 0 or 1; R is a bis(lower alkoxycarbonyl)methyl, etc., when m=0 and R is a group of the formula S-(O)1 -R (R is a lower alkyl, etc.; (1) is 0, 1 or 2)] such as 7-chloro-2-(4-ethylthiomethylphenyl)-3-methyl-4(3H)- quinazolinone. The compound of formula II is halogenated and reacted with a compound of the formula R -H (R is SR ) to obtain a compound of formula I, in which, for example, (m) is 1 and (1) is 0.

5. 发明专利

JPH09286792A PHOSPHONIC DIESTER DERIVATIVE 失效
公开(公告)号：JPH09286792A
公开(公告)日：1997-11-04
申请号：JP3361697
申请日：1997-02-18
申请人： OTSUKA PHARMA FACTORY INC
发明人： SAKAI YASUHIRO , KUROKI YASUHISA , MIYATA KAZUYOSHI , TSUDA YOSHIHIKO , SHIBUYA NAOMASA , KAWAMURA KENICHI , INOUE YASUHIDE , SATO KEIGO , MIKI SHINYA
IPC分类号： A61K31/66 , A61P3/08 , A61P3/10 , C07F9/6512 , C07F9/6558
摘要： PROBLEM TO BE SOLVED: To obtain the subject new compound derivative, which is a specific phosphonic diester derivative having the quinazolinone skeleton, having hypoglycemic actions and capable of manifesting excellent efficacies with a low dose and useful as an active ingredient, etc., of a medicine such as a therapeutic agent for diabetes. SOLUTION: This new phosphonic diester derivative is represented by formula I (R to R are each H, a halogen, a lower alkyl, a lower alkoxy, amino, nitro, etc.; R is a lower alkyl, a lower alkenyl, phenyl, etc.; R and R are each a lower alkyl; A is a thiophene ring, a pyrazine ring, a lower alkylene or a single bond) and is capable of manifesting hypoglycemic actions and excellent efficacies with a low dose and useful as a therapeutic agent, etc., for diabetes. This compound is obtained by reacting 2-amino-N-substituted benzamides represented by formula II with a dialkoxyphosphorylcarboxylic acid halide represented by formula III (X is a halogen) in the presence of a deacidifying agent in a solvent and then carrying out the cyclizing reaction of the reactional product.

6. 发明专利

AU6855894A Phosphonic diester derivative 未知
公开(公告)号：AU6855894A
公开(公告)日：1995-01-17
申请号：AU6855894
申请日：1994-05-31
申请人： OTSUKA PHARMA FACTORY INC
发明人： KUROGI YASUHISA , MIYATA KAZUYOSHI , NAKAMURA SHIZUO , KONDO MITSUYOSHI , IWAMOTO TAKESHI , NABA CHIEKO , TSUDA YOSHIHIKO , INOUE YASUHIDE , KANAYA JUN , SATO KEIGO
IPC分类号： C07F9/6512 , C07F9/6558 , A61K31/675
摘要： A phosphonic diester derivative represented by general formula (1) and useful as remedies for hyperlipidemia, hypertension, diabetes, and so forth. In said formula, A represents oxygen or sulfur; R , R , R and R represent each independently hydrogen, lower alkoxy, nitro, lower alkyl, halogenated lower alkyl or halogen; R represents phenyl, -B-R (wherein B represents oxygen or sulfur; and R represents hydrogen, lower alkyl, cycloalkyl, phenyl, phenylated lower alkyl wherein the phenyl may be halogenated, phenoxylated lower alkyl, lower-alkoxy carbonyl-subsituted lower alkyl, carboxylated lower alkyl or lower alkenyl) or -NR R (wherein R and R represent each independently hydrogen, lower alkyl, amino or cycloakyl, or R and R are combined together to form lower alkylene); and R and R represent each independently hydrogen or lower alkyl.

7. 发明专利

AU1173497A Phosphonic acid diester derivatives 未知
公开(公告)号：AU1173497A
公开(公告)日：1997-07-28
申请号：AU1173497
申请日：1996-12-24
申请人： OTSUKA PHARMA FACTORY INC
发明人： MIYATA KAZUYOSHI , SAKAI YASUHIRO , SHOJI YASUO , TSUDA YOSHIHIKO , INOUE YASUHIDE , SATO KEIGO , MIKI SHINYA
IPC分类号： C07F9/6509 , C07F9/6539 , C07F9/6553 , C07F9/6558 , C07F9/6561 , A61K31/67 , A61K31/675
摘要： Phosphonic acid diester derivatives represented by general formula (1) which are useful as a remedy for hyperlipidemia and diabetes, an antitumour agent and a preventive or remedy for cataract, wherein R represents cycloalkyl, etc.; R represents hydrogen, phenyl or lower alkyl; R and R represent each lower alkyl; and A represents a heterocycle selected from among pyrazine, thiophene and phenyl-substituted thiazole rings.

8. 发明专利

AU1824495A Phosphonic diester derivative 未知
公开(公告)号：AU1824495A
公开(公告)日：1995-09-25
申请号：AU1824495
申请日：1995-02-27
申请人： OTSUKA PHARMA FACTORY INC
发明人： KUROKI YASUHISA , MIYATA KAZUYOSHI , TSUDA YOSHIHIKO , INOUE YASUHIDE , KANAYA JUN , SATO KEIGO
IPC分类号： C07F9/6512 , C07D239/86 , C07D239/91 , A61K31/505
摘要： The invention provides a phosphonic diester derivative of the formula: wherein R , R , R and R are the same or different and each represents a hydrogen atom, a lower alkyl group, a halogen atom, a nitro group, a lower alkoxy group, a cyano group, a phenylsulfonylamino group, a benzoylamino group, an amino group or a halogen-substituted lower alkyl group, R represents a phenyl group, a lower alkyl group, a phenyl(lower)alkyl group optionally substituted by halogen on the phenyl ring, a lower alkenyl group, a carboxy(lower)alkyl group, a (lower)alkoxy-carbonyl(lower)alkyl group, a (lower)alkoxy(lower)alkyl group, a lower alkynyl group, a benzoyl(lower)alkyl group, an amino group, a di(lower)alkanoylamino group, a benzylideneamino group optionally having lower alkoxy on the phenyl ring or a pyridylmethylideneamino group, R represents a lower alkyl group, R represents a lower alkoxy group, a hydroxyl group, a phenyl group, a phenyl(lower)alkoxy group optionally having halogen on the phenyl ring or a phenyl(lower)alkylamino group, X and X independently represent an oxygen atom or a sulfur atom, A represents an oxygen atom or a single bond, and Z represents a lower alkylene group. The derivatives according to the invention are useful as therapeutic or preventive compositions for hyperlipidemia, hypertension, and diabetes.

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