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1. 发明专利

IT1147016B 未知
公开(公告)号：IT1147016B
公开(公告)日：1986-11-19
申请号：IT4936280
申请日：1980-07-28
申请人： NIPPON KAYAKU KK
发明人： TAKEI YUKIO , YOSHIDA MASAO , NISHIZAWA RINZO
IPC分类号： C07D237/32 , C07D307/88 , C07D
摘要： A novel process for producing 7-alkoxycarbonyl-6,8-dimethyl-4-hydroxymethyl-1-phthalazone, and its intermediates. 7-Alkoxycarbonyl-6,8-dimethyl-4-hydroxymethyl-1-phthalazone can be obtained by reacting substituted methylenetriphenylphosphorane with 3,5-dimethyl-4-alkoxycarbonylphthalic anhydride to obtain 6-alkoxycarbonyl-5,7-dimethyl- DELTA 3, alpha -substituted methylenephthalide, reacting the latter with hydrazine to obtain a phthalazone derivative, hydrolyzing the latter, halogenating the hydrolyzate to obtain 7-alkoxycarbonyl-6,8-dimethyl-4-( alpha -halogeno- alpha -substituted methyl)-1-phthalazone and then directly hydrolyzing and decarboxylating the latter or, when said 7-alkoxycarbonyl-6,8-dimethyl-4-( alpha -halogeno- alpha -substituted methyl)-1-phthalazone is 7-alkoxycarbonyl-6,8-dimethyl-1-phthalazone-4- alpha -halogenoacetic acid, reacting it with a carboxylic acid salt such as sodium acetate and simultaneously decarboxylating the acyloxylated compound and then hydrolyzing the decarboxylated product or firstly decarboxylating the 1-phthalazone-4- alpha -halogenoacetic acid derivative, reacting the decarboxylated product with said carboxylic acid salt and then hydrolyzing the reaction product or when said 7-alkoxycarbonyl-6,8-dimethyl-4-( alpha -halogeno- alpha -substituted methyl)-1-phthalazone is 7-alkoxycarbonyl-4-( alpha -carbamoyl- alpha -halogenomethyl)-6,8-dimethyl-1-phthalazone, reacting it with said carboxylic acid salt and then hydrolyzing and decarboxylating the acyloxylated compound simultaneously.

2. 发明专利

IT8225026D0 未知
公开(公告)号：IT8225026D0
公开(公告)日：1982-12-29
申请号：IT2502682
申请日：1982-12-29
申请人： NIPPON KAYAKU KK
发明人： ISHIKAWA MASAYUKI , ITOH SHIGERU , YOSHIZAWA JUNJI , TAKEZAWA HIROSHI , IHARA MASAKI , NISHIZAWA RINZO , SUGIMURA HIDEO , YOSHIDA MASAO
IPC分类号： A61K31/50 , A61K31/502 , A61K31/675 , A61P7/02 , A61P9/12 , C07D237/32 , C07F9/6509

3. 发明专利

DK162288B 未知
公开(公告)号：DK162288B
公开(公告)日：1991-10-07
申请号：DK496379
申请日：1979-11-22
申请人： NIPPON KAYAKU KK
发明人： UMEZAWA HAMAO , AOYAGI TAKAAKI , SHIRAI TADASHI , NISHIZAWA RINZO , SUZUKI MASAO , SAINO TETSUSHI
IPC分类号： A47L13/40 , A61K20060101 , A61K31/16 , A61K31/195 , C07C20060101 , C07C51/347 , C07C233/31 , C07C233/47 , C07C233/76 , C07C233/87 , C07C271/22 , C07C271/34 , C07C271/54 , C07D209/48 , C07K1/06 , C07K5/02 , C07K5/06

4. 发明专利

CH645360A5 VERFAHREN ZUR HERSTELLUNG VON 7-ALKOXYCARBONYL-6,8-DIMETHYL-4-HYDROXYMETHYL-1-PHTHALAZON. 未知
公开(公告)号：CH645360A5
公开(公告)日：1984-09-28
申请号：CH577580
申请日：1980-07-29
申请人： NIPPON KAYAKU KK
发明人： TAKEI YUKIO , YOSHIDA MASAO , NISHIZAWA RINZO
IPC分类号： C07D237/32 , C07D307/88

5. 发明专利

GB2112389A Esters of 4-hydroxymethyl-1- phthalazones 未知
公开(公告)号：GB2112389A
公开(公告)日：1983-07-20
申请号：GB8236624
申请日：1982-12-23
申请人： NIPPON KAYAKU KK , BANYU PHARMA CO LTD
发明人： ISHIKAWA MASAYUKI , ITO SHIGERU , YOSHIZAWA JUNJI , TAKEZAWA HIROSHI , IHARA MASAKI , NISHIZAWA RINZO , SUGIMURA HIDEO , YOSHIDA MASAO
IPC分类号： A61K31/50 , A61K31/502 , A61K31/675 , A61P7/02 , A61P9/12 , C07D237/32 , C07F9/6509 , A61K31/495 , C07D403/12 , C07F9/65
摘要： Esters of 4-hydroxymethyl-1- phthalazones useful for treating cerebral apoplexy, cerebral thrombosis and atherosclerosis are compounds having the general formula wherein R1 is a C1-C6 alkyl group and R2 is -SO3H, wherein R3 is hydrogen, alkyl, aryl or aralkyl, or wherein W is a group formed by removal of a hydrogen atom from a ring of a cyclic imine of 4 or 5 carbon atoms which may be substituted by hydroxyl or a residual group represented by the formula wherein X is a residual group which may be substituted formed by removal of 3 hydrogen atoms from an alkane, alkene, cycloalkane or aromatic hydrocarbon of 6 to 12 carbon atoms; one of Y and Z is hydrogen or carboxyl, amine or substituted amine and the other is carboxyl, amine or substituted amine; or are physiologically acceptable salts thereof.

6. 发明专利

FR2462429A1 未知
公开(公告)号：FR2462429A1
公开(公告)日：1981-02-13
申请号：FR8016862
申请日：1980-07-30
申请人： NIPPON KAYAKU KK
发明人： TAKEI YUKIO , YOSHIDA MASAO , NISHIZAWA RINZO
IPC分类号： C07D237/32 , C07D307/88 , A61K31/495
摘要： A novel process for producing 7-alkoxycarbonyl-6,8-dimethyl-4-hydroxymethyl-1-phthalazone, and its intermediates. 7-Alkoxycarbonyl-6,8-dimethyl-4-hydroxymethyl-1-phthalazone can be obtained by reacting substituted methylenetriphenylphosphorane with 3,5-dimethyl-4-alkoxycarbonylphthalic anhydride to obtain 6-alkoxycarbonyl-5,7-dimethyl- DELTA 3, alpha -substituted methylenephthalide, reacting the latter with hydrazine to obtain a phthalazone derivative, hydrolyzing the latter, halogenating the hydrolyzate to obtain 7-alkoxycarbonyl-6,8-dimethyl-4-( alpha -halogeno- alpha -substituted methyl)-1-phthalazone and then directly hydrolyzing and decarboxylating the latter or, when said 7-alkoxycarbonyl-6,8-dimethyl-4-( alpha -halogeno- alpha -substituted methyl)-1-phthalazone is 7-alkoxycarbonyl-6,8-dimethyl-1-phthalazone-4- alpha -halogenoacetic acid, reacting it with a carboxylic acid salt such as sodium acetate and simultaneously decarboxylating the acyloxylated compound and then hydrolyzing the decarboxylated product or firstly decarboxylating the 1-phthalazone-4- alpha -halogenoacetic acid derivative, reacting the decarboxylated product with said carboxylic acid salt and then hydrolyzing the reaction product or when said 7-alkoxycarbonyl-6,8-dimethyl-4-( alpha -halogeno- alpha -substituted methyl)-1-phthalazone is 7-alkoxycarbonyl-4-( alpha -carbamoyl- alpha -halogenomethyl)-6,8-dimethyl-1-phthalazone, reacting it with said carboxylic acid salt and then hydrolyzing and decarboxylating the acyloxylated compound simultaneously.

7. 发明专利

DE2812041A1 未知
公开(公告)号：DE2812041A1
公开(公告)日：1978-09-28
申请号：DE2812041
申请日：1978-03-20
申请人： NIPPON KAYAKU KK
发明人： TASHIRO YASUHISA , NAGASHIMA TAKASHI , AOKI SHIGERU , NISHIZAWA RINZO
IPC分类号： C07B57/00 , C07B31/00 , C07C59/50 , C07C67/00 , C07C227/00 , C07C227/18 , C07C227/34 , C07C229/08 , C07C313/00 , C07C323/58 , C07C101/04 , C07C149/247 , C07C65/135
摘要： Two optically active amino acid-mandelic acid complexes are obtained by interacting in a solvent under pH conditions of 1.0-4.0 an amino acid expressed by a general formula (in which R represents a methyl group, an ethyl group or a methylthioethyl group) and mandelic acid, one of the acids being an optically active substance and the other being a racemic modification, and optically resolving the resulting complexes into two diastereoisomers by using solubility difference therebetween. The optically active complexes are each decomposed by means of an acid, a strongly acidic ion-exchange resin, or a weakly basis ion-exchange resin to obtain optically active amino acids or optically active mandelic acid.

8. 发明专利

IT1211147B 未知
公开(公告)号：IT1211147B
公开(公告)日：1989-09-29
申请号：IT2561481
申请日：1981-12-15
申请人： NIPPON KAYAKU KK
发明人： UMEZAWA HAMAO , AOYAGI TAKAAKI , SHIRAI TADASHI , NISHIZAWA RINZO , SUZUKI MASAO , SAINO TETSUSHI
IPC分类号： A47L13/40 , A61K20060101 , A61K31/16 , A61K31/195 , C07C20060101 , C07C51/347 , C07C233/31 , C07C233/47 , C07C233/76 , C07C233/87 , C07C271/22 , C07C271/34 , C07C271/54 , C07D209/48 , C07K1/06 , C07K5/02 , C07K5/06 , A61K

9. 发明专利

IT1194593B 未知
公开(公告)号：IT1194593B
公开(公告)日：1988-09-22
申请号：IT2748779
申请日：1979-11-22
申请人： NIPPON KAYAKU KK
发明人： UMEZAWA HAMAO , AOYAGI TAKAAKI , SHIRAI TADASHI , NISHIZAWA RINZO , SUZUKI MASAO , SAINO TETSUSHI
IPC分类号： A47L13/40 , A61K20060101 , A61K31/16 , A61K31/195 , C07C20060101 , C07C51/347 , C07C233/31 , C07C233/47 , C07C233/76 , C07C233/87 , C07C271/22 , C07C271/34 , C07C271/54 , C07D209/48 , C07K1/06 , C07K5/02 , C07K5/06 , A61K

10. 发明专利

CA1182125A PROCESS FOR PRODUCING THREO-3-AMINO-2- HYDROXYBUTANOYL-AMINOACETIC ACIDS, AS WELL AS NOVEL INTERMEDIATES THEREFOR AND PROCESS FOR PRODUCING THEM 未知
公开(公告)号：CA1182125A
公开(公告)日：1985-02-05
申请号：CA340428
申请日：1979-11-22
申请人： NIPPON KAYAKU KK
发明人： UMEZAWA HAMAO , AOYAGI TAKAAKI , SHIRAI TADASHI , NISHIZAWA RINZO , SUZUKI MASAO , SAINO TETSUSHI
IPC分类号： A47L13/40 , A61K20060101 , A61K31/16 , A61K31/195 , C07C20060101 , C07C51/347 , C07C233/31 , C07C233/47 , C07C233/76 , C07C233/87 , C07C271/22 , C07C271/34 , C07C271/54 , C07D209/48 , C07K1/06 , C07K5/02 , C07K5/06 , C07C101/78 , C07C125/065
摘要： A process for producing threo-3-amino-2-hydroxybutanoyl-aminoacetic acids comprises the steps of allowing to react a starting compound represented by the general formula: (I), wherein R1 represents a naphthyl or a group of the formula: in which R6 and R7 represent individually hydrogen, halogen, amino or a protected amino, hydroxy or a protected hydroxy, a lower alkoxy, a lower alkyl or phenyl and R2 represents a protected amino, with a starting compound represented by the general formula: (II), wherein R3 represents hydrogen or an ester residue, to obtain threo-3-protected amino-2-hydroxy-4-oxobutanoic acid or its ester represented by the general formula: (III), wherein R1, R2 and R3 have the same meanings as above, and then reducing the same into threo-3-protected arnino-2-hydroxybutanoic acid or its ester represented by the general formula: (IV), wherein R1, R2 and R3 have the same meanings as above, and further converting the above compound into threo -3-amino-2-hydroxybutanoic acid represented by the general formula; (V), wherein R? represents amino or a protected amino, thereafter condensing the same, in a conventional manner for forming a peptide bond, with a compound represented by the general formula: (VI), wherein R4 represents all alkyl having 3 - 4 carbon atom or 3-guanidinopropyl, while previously protecting as required those groups not relevant to the reaction, and removing the protecting groups for the functional groups to produce threo-3-amino-2-hydroxybutanoylaminoacetic acids represented by the general formula: (VII), wherein R1 and R4 have the same meanings as above. This invention also provides the compounds represented by the general formula (III) as novel intermediates for the above aimed compounds and a process for producing the intermediates.

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