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1. 发明授权

US4837316A Alkylamide derivatives with H.sub.2 -receptor antagonistic and cytoprotective action 失效
标题翻译：具有H2受体拮抗和细胞保护作用的烷基酰胺衍生物
公开(公告)号：US4837316A
公开(公告)日：1989-06-06
申请号：US900752
申请日：1986-08-27
申请人： Yasuo Sekine , Nobuhiro Hirakawa , Noriaki Kashiwaba , Tetsuaki Yamaura , Hisako Harada , Teruo Kutsuma , Hajime Matsumoto , Akihiro Sekine , Yoshikazu Isowa
发明人： Yasuo Sekine , Nobuhiro Hirakawa , Noriaki Kashiwaba , Tetsuaki Yamaura , Hisako Harada , Teruo Kutsuma , Hajime Matsumoto , Akihiro Sekine , Yoshikazu Isowa
IPC分类号： C07D213/32 , C07D213/38 , C07D213/61 , C07D213/65 , C07D213/70 , C07D213/79 , C07D239/38 , C07D277/64 , C07D277/74 , C07D285/12 , C07D285/135 , C07D295/096 , C07D307/38 , C07D307/52 , C07D307/68 , C07D317/56 , C07D333/18 , C07D333/28 , C07D333/38 , C07D405/12 , C07D409/12 , C07D413/12 , C07D417/12
CPC分类号： C07D213/70 , C07D213/32 , C07D213/38 , C07D213/61 , C07D213/65 , C07D213/79 , C07D239/38 , C07D277/64 , C07D277/74 , C07D285/135 , C07D295/096 , C07D307/38 , C07D307/52 , C07D307/68 , C07D317/56 , C07D333/18 , C07D333/28 , C07D333/38 , C07D405/12 , C07D409/12 , C07D413/12 , C07D417/12
摘要： Alkylamide derivatives having the formula, These compounds have a strong antiulcer action depend on histamine H.sub.2 -receptor antagonistic action and a cytoprotective action upon gastric mucous membrance.
摘要翻译：具有下式的烷基酰胺衍生物这些化合物具有很强的抗溃疡作用，取决于组胺H2受体拮抗作用和对胃粘膜的细胞保护作用。

2. 发明授权

US4912101A 4-aminomethyl-pyridyl-2-oxy derivatives having anti-ulcer activity 失效
标题翻译：具有抗溃疡活性的4-氨基甲基 - 吡啶-2-基氧基衍生物
公开(公告)号：US4912101A
公开(公告)日：1990-03-27
申请号：US166022
申请日：1988-03-09
申请人： Nobuhiko Hirakawa , Noriaki Kashiwaba , Hajime Matsumoto , Akihiko Hosoda , Yasuo Sekine , Yoshikazu Isowa , Tetsuaki Yamaura , Akihiro Sekine , Masashi Nishikawa
发明人： Nobuhiko Hirakawa , Noriaki Kashiwaba , Hajime Matsumoto , Akihiko Hosoda , Yasuo Sekine , Yoshikazu Isowa , Tetsuaki Yamaura , Akihiro Sekine , Masashi Nishikawa
IPC分类号： C07D213/64 , C07D405/12 , C07D405/14
CPC分类号： C07D213/64 , C07D405/12 , C07D405/14
摘要： A compound represented by the following formula or a salt thereof ##STR1## wherein each of R.sub.1 and R.sub.2 represents a lower alkyl group, or R.sub.1 and R.sub.2, together with the nitrogen atom to which they are bonded, may form a substituted or unsubstituted, saturated or partially unsaturated 4- to 8-membered heterocyclic group which may contain a hetero atom selected from N, O and S, Y represents a group of the formula --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, and n is 0, 1 or 2. This compound is useful as anti-peptic ulcer agent.

3. 发明授权

US4977267A Intermediates for pyridyloxy compounds having utility as anti-peptic ulcer agents 失效
标题翻译：用作抗消化性溃疡剂的吡啶氧基化合物的中间体
公开(公告)号：US4977267A
公开(公告)日：1990-12-11
申请号：US301856
申请日：1989-01-26
申请人： Nobuhiko Hirakawa , Noriaki Kashiwaba , Hajime Matsumoto , Akihiko Hosoda , Yasuo Sekine , Yoshikazu Isowa , Tetsuaki Yamura , Akihiro Sekine , Masashi Nishikawa
发明人： Nobuhiko Hirakawa , Noriaki Kashiwaba , Hajime Matsumoto , Akihiko Hosoda , Yasuo Sekine , Yoshikazu Isowa , Tetsuaki Yamura , Akihiro Sekine , Masashi Nishikawa
IPC分类号： C07D213/64 , C07D405/12 , C07D405/14
CPC分类号： C07D213/64 , C07D405/12 , C07D405/14
摘要： The compounds of the formulas (VI) and (VII) are useful intermediates in producing pyridyloxy derivatives of the formula (I), such as, for instance, N-{4-[4-(piperidinomethyl)pyridyl-2-oxy]-2-butenyl}-2-(furfurylthio)acetamide, which are useful as anti-peptic ulcer agents. The compounds of formula (VI) have the formula ##STR1## wherein A represents a formyl group, a protected formyl group, a hydroxymethyl group or a protected hydroxymethyl group. The compounds of formula (VIII) have the formula ##STR2## wherein G represents a formyl group, a protected formyl group, a hydroxymethyl group, a hydroxymethyl group in which the hydroxyl group is protected, or a halogenomethyl group, Y represents --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, and n is 0, 1 or 2.

4. 发明授权

US4165311A Addition compound of dipeptide derivative and amino acid derivative 失效
标题翻译：二肽衍生物和氨基酸衍生物的加成化合物
公开(公告)号：US4165311A
公开(公告)日：1979-08-21
申请号：US870108
申请日：1978-01-17
申请人： Yoshikazu Isowa , Muneki Ohmori , Kaoru Mori , Tetsuya Ichikawa , Yuji Nonaka , Keiichi Kihara , Kiyotaka Oyama , Heijiro Satoh , Shigeaki Nishimura
发明人： Yoshikazu Isowa , Muneki Ohmori , Kaoru Mori , Tetsuya Ichikawa , Yuji Nonaka , Keiichi Kihara , Kiyotaka Oyama , Heijiro Satoh , Shigeaki Nishimura
IPC分类号： C07K5/072 , C07K5/075 , C07C103/52 , C12B1/00
CPC分类号： C07K5/0613
摘要： Addition compounds having the formula ##STR1## wherein R.sub.1 represents an aliphatic oxycarbonyl group, benzyloxycarbonyl group which can have nuclear substituents, or benzoyl, aromatic sulfonyl or aromatic sulfinyl group; R.sub.2 represents methyl, isopropyl, isobutyl, isoamyl or benzyl group; R.sub.3 represents a lower alkoxyl, benzyloxy or benzhydryloxy group and n represents 1 or 2 together with methods for preparing (I) and for decomposing (I) into the constituent dipeptide esters and amino acid esters.
摘要翻译：具有式（I）的加成化合物，其中R 1表示脂族氧基羰基，可具有核取代基的苄氧基羰基，或苯甲酰基，芳族磺酰基或芳族亚磺酰基; R 2表示甲基，异丙基，异丁基，异戊基或苄基; R3表示低级烷氧基，苄氧基或二苯甲氧基，n表示1或2，以及用于制备（I）和用于将（I）分解成组分二肽酯和氨基酸酯的方法。

5. 发明授权

US4017512A Process for producing N-alkylhydroxylamines 失效
标题翻译： N-烷基羟胺的制备方法
公开(公告)号：US4017512A
公开(公告)日：1977-04-12
申请号：US592310
申请日：1975-07-01
申请人： Yoshikazu Isowa , Hideaki Kurita
发明人： Yoshikazu Isowa , Hideaki Kurita
IPC分类号： C07D209/34 , C07C83/00 , C07C83/02 , C07C83/08
摘要： A novel process for producing an N-alkylhydroxylamine of the formula (I)rnh-oh (i)wherein R represents an alkyl group which may be substituted with least one substituent, which comprises reacting an N-mesyl-O-(p-alkoxybenzyl)hydroxylamine or an N-mesyl-O-(2,4,6-trialkylbenzyl)hydroxylamine with an alkyl halide of the formula (III)rx (iii)wherein R is as defined above and X represents a halogen atom, under a basic condition to produce the corresponding N-alkyl-N-mesyl-O-(p-alkoxybenzyl)hydroxylamine or N-alkyl-N-mesyl-O-(2,4,6-trialkylbenzyl)hydroxylamine, and treating the resulting compound with a solution of a phenol compound, and novel N-alkyl-N-mesyl-O-(p-alkoxybenzyl)hydroxyl amines and N-alkyl-N-mesyl-O-(2,4,6-trialkylbenzyl)hydroxylamines which are useful as intermediates in the above process.
摘要翻译：一种制备式（I）的N-烷基羟胺的新方法RNH-OH（I）其中R表示可以被至少一个取代基取代的烷基，其包括使N-甲磺酰基-O-（对 - ）羟胺或N-甲磺酰基-O-（2,4,6-三烷基苄基）羟胺与式（III）的卤代烷（其中R如上定义，X表示卤素原子）的式制备相应的N-烷基-N-甲磺酰基-O-（对 - 烷氧基苄基）羟胺或N-烷基-N-甲磺酰基-O-（2,4,6-三烷基苄基）羟胺的条件，并将所得化合物用酚化合物的溶液和新的N-烷基-N-甲磺酰基-O-（对 - 烷氧基苄基）羟胺和N-烷基-N-甲磺酰基-O-（2,4,6-三烷基苄基）羟胺，其可用作中间体在上述过程中。

6. 发明授权

US4119493A Process for producing a peptide 失效
标题翻译：生产肽的方法
公开(公告)号：US4119493A
公开(公告)日：1978-10-10
申请号：US803350
申请日：1977-06-03
申请人： Yoshikazu Isowa , Muneki Ohmori , Hideaki Kurita , Tetsuya Ichikawa , Masanari Sato , Kaoru Mori
发明人： Yoshikazu Isowa , Muneki Ohmori , Hideaki Kurita , Tetsuya Ichikawa , Masanari Sato , Kaoru Mori
IPC分类号： A61K38/00 , C07K1/02 , C07K5/06 , C07K5/072 , C07K5/078 , C07K5/083 , C07K5/093 , C07K5/097 , C07K5/103 , C07K5/107 , C07K5/113 , C12P21/02 , C12D13/06
CPC分类号： C12P21/02 , C07K1/02 , C07K5/06043 , C07K5/06095 , C07K5/06104 , C07K5/06113 , C07K5/06147 , C07K5/0804 , C07K5/0819 , C07K5/1008 , C07K5/1013 , C07K5/1016 , C07K5/1021 , A61K38/00 , Y02P20/55 , Y10S435/832 , Y10S435/837 , Y10S435/839 , Y10S435/842 , Y10S435/873 , Y10S435/886 , Y10S435/896 , Y10S435/897 , Y10S435/918
摘要： A peptide having the formulaX--A--B--Ywherein A and B are the same or different and represent an amino acid residue or a peptide residue; X represents an amino protective group and Y represents a carboxyl protective group, is prepared by reacting an amino acid or peptide having an N-terminal protective group or a salt thereof of the formula:X--A--OHwith an amino acid or peptide having a C-terminal protective group or a salt thereof of the formula:H--B--Yin the presence of metalloproteinase in an aqueous solution having a pH which maintains the enzyme activity of said metalloproteinase.
摘要翻译：具有式X-A-B-Y的肽，其中A和B相同或不同，代表氨基酸残基或肽残基; X表示氨基保护基，Y表示羧基保护基，通过使具有下式的N-末端保护基的氨基酸或肽或其盐反应来制备：

7. 发明授权

US5349050A Peptides, and antidementia agents containing the same 失效
标题翻译：肽，和含有它们的抗增生剂
公开(公告)号：US5349050A
公开(公告)日：1994-09-20
申请号：US838140
申请日：1992-02-18
申请人： Mitsuo Masaki , Masaki Uehara , Kenji Hirate , Yoshikazu Isowa , Yoshiaki Sato , Yoshiharu Nakashima
发明人： Mitsuo Masaki , Masaki Uehara , Kenji Hirate , Yoshikazu Isowa , Yoshiaki Sato , Yoshiharu Nakashima
IPC分类号： A61K38/00 , C07K5/02 , C07K5/103 , C07K5/117 , C07K7/16 , A61K31/34 , A61K31/02 , C07K5/10 , C07K7/06
CPC分类号： C07K5/0202 , C07K5/1013 , C07K5/1024 , C07K7/16 , A61K38/00
摘要： Disclosed is a novel peptide having one of the formulae: ##STR1## (A and B are the amino acids: wherein if A is D- or L-Pro, B is Hat or Cit;if A is D-Pro, B is D-Arg, andif B is D- or L-Arg, A is Sat, Pip, Aze or Arg)Asn-A-L- (D-)Pro-Arg- (Gly)n (A is Set, Thr or Ala, n is 1 or 0)A-Ser-Pip-Arg (A is Pro-Asn-, Asn- or Pro-) ##STR2## (A is cyclopentylcarbonyl, Pro or pGlu; B is Gly or .beta.-Ala, W is a hydrogen atom or a group having the formula:or a peptide having the formula: ##STR3## wherein A and B have the same meanings as mentioned above, respectively pGlu-Asn-Ser-A-B-(Gly)n (A is Aze, D- or L-Pro, Pip or Sat, B is D- or L-Arg, Cit, Hat, Lys or Orn, n is 1 or 0) andPro- (Ash)m-Set-L- (D-)Pro-Arg- (Gly) n (m and n are independently 0 or 1)their functional derivatives, and pharmaceutically acceptable salts thereof.
摘要翻译：公开了具有下式之一的新肽：（A和B是氨基酸：其中如果A是D-或L-Pro，B是Hat或Cit;如果A是D-Pro，B是D -Arg，如果B为D-或L-Arg，A为Sat，Pip，Aze或Arg）Asn-AL-（D-）Pro-Arg-（Gly）n（A为Set，Thr或Ala，n （A为Pro-Asn-，Asn-或Pro-）A（A为环戊基羰基，Pro或pGlu; B为Gly或β-Ala，W为氢原子或具有下式的基团：或具有下式的肽：其中A和B分别具有与上述相同的含义，分别为pGlu-Asn-Ser-AB-（Gly）n（A为Aze，D- 或L-Pro，Pip或Sat，B为D-或L-Arg，Cit，Hat，Lys或Orn，n为1或0）和Pro-（Ash）m-Set-L-（D- Arg-（Gly）n（m和n独立地为0或1）它们的官能衍生物及其药学上可接受的盐。

8. 发明授权

US5112947A Peptides, and antidementia agents containing the same 失效
标题翻译：肽，以及含有它的抗生素代谢物
公开(公告)号：US5112947A
公开(公告)日：1992-05-12
申请号：US509950
申请日：1990-04-16
申请人： Mitsuo Masaki , Masaki Uehara , Kenji Hirate , Yoshikazu Isowa , Yoshiaki Sato , Yoshiharu Nakashima
发明人： Mitsuo Masaki , Masaki Uehara , Kenji Hirate , Yoshikazu Isowa , Yoshiaki Sato , Yoshiharu Nakashima
IPC分类号： A61K38/00 , C07K5/02 , C07K5/103 , C07K5/117 , C07K7/16
CPC分类号： C07K5/0202 , C07K5/1013 , C07K5/1024 , C07K7/16 , A61K38/00
摘要： Disclosed is a novel peptide having one of the formulae: ##STR1## (A and B are the amino acids: wherein if A is D- or L-Pro, B is Har or Cit;if A is D-Pro, B is D-Arg, andif B is D- or L-Arg, A is Sar, Pip, Aze or Arg)Asn-A-L-(D-)Pro-Arg-(Gly).sub.n(A is Ser, Thr or Ala, n is 1 or 0)A-Ser-Pip-Arg(A is Pro-Asn-, Asn- or Pro-) ##STR2## (A is cyclopentylcarbonyl, Pro or pGlu; B is Gly or .beta.-Ala, W is a hydrogen atom or a group having the formula: or a peptide having the formula: ##STR3## wherein A and B have the same meanings as mentioned above, respectivelypGlu-Asn-Ser-A-B-(Gly).sub.n(A is Aze, D- or L-Pro, Pip or Sar, B is D- or L-Arg, Cit, Har, Lys or Orn, n is 1 or 0) andPro-(Asn).sub.m -Ser-L-(D-)Pro-Arg-(Gly).sub.n(m and n are independently 0 or 1)their functional derivatives, and pharmaceutically acceptable salts thereof.

9. 发明授权

US3972773A Process for producing peptide 失效
标题翻译：生产肽的方法
公开(公告)号：US3972773A
公开(公告)日：1976-08-03
申请号：US572630
申请日：1975-04-29
申请人： Yoshikazu Isowa , Takeshi Nagasawa , Katsumasa Kuroiwa , Koichi Narita
发明人： Yoshikazu Isowa , Takeshi Nagasawa , Katsumasa Kuroiwa , Koichi Narita
IPC分类号： A61K38/00 , C07K1/02 , C07K5/06 , C07K5/072 , C07K5/078 , C07K5/083 , C07K5/093 , C07K5/097 , C07K5/103 , C07K5/107 , C07K5/113 , C07K7/06 , C12P21/02 , C12D13/06
CPC分类号： C07K7/06 , C07K1/02 , C07K5/06043 , C07K5/06095 , C07K5/06104 , C07K5/06113 , C07K5/06147 , C07K5/0804 , C07K5/0819 , C07K5/1008 , C07K5/1013 , C07K5/1016 , C07K5/1021 , C12P21/02 , A61K38/00 , Y02P20/55
摘要： A peptide having the formula:X-A-B-C-YwhereinA represents Ala., Gln., Asn., .omega.-BOC-Lys., Leu., Gly., Glu., ##EQU1## OR A represents A.sub.1 -- A.sub.2 wherein A.sub.1 represents a hydrophilic amino acid residue and A.sub.2 represents Val., Met., Leu. or Gln.;B represents Phe., Tyr., Leu., Met., Glu., Asp., Gln., Asn or Trp.;C represents Phe., Leu., Ileu., Try., Cys-SBzl., Ser-OBzl., Trp. or Met.;X represents an .alpha.-amino acid protective group; an amino acid residue having an N-terminal protective group or a peptide residue having an N-terminal protective group; Y represents a carboxyl protective group, an amino acid residue having a C-terminal protective group or a peptide residue having a C-terminal group, is produced in a process which comprises reacting a peptide having the formulaX-A-B-OHwith an amino acid or a peptide having the formulaH-C-Yin the presence of enzyme pepsin.
摘要翻译：具有下式的肽：

10. 发明授权

US4436925A Addition compound of dipeptide derivative and amino acid derivative 失效
标题翻译：二肽衍生物和氨基酸衍生物的加成化合物
公开(公告)号：US4436925A
公开(公告)日：1984-03-13
申请号：US270025
申请日：1982-06-03
申请人： Yoshikazu Isowa , Muneki Ohmori , Kaoru Mori , Tetsuya Ichikawa , Yuji Nonaka , Keiichi Kihara , Kiyotaka Oyama , Heijiro Satoh , Shigeaki Nishimura
发明人： Yoshikazu Isowa , Muneki Ohmori , Kaoru Mori , Tetsuya Ichikawa , Yuji Nonaka , Keiichi Kihara , Kiyotaka Oyama , Heijiro Satoh , Shigeaki Nishimura
IPC分类号： C07K5/072 , C07K5/075 , C07C101/00
CPC分类号： C07K5/0613
摘要： Addition compounds have the formula ##STR1## wherein R.sub.1 represents an aliphatic oxycarbonyl group, benzyloxycarbonyl group which can have nuclear substituents or benzoyl, aromatic sulfonyl or aromatic sulfinyl group; R.sub.2 represents methyl, isopropyl, isobutyl, isoamyl or benzyl group; R.sub.3 represents a lower alkoxyl, benzyloxy or benzhydryloxy group and n represents 1 or 2.The addition compounds are produced by reacting an N-substituted monoaminodicarboxylic acid having the formula ##STR2## with an amino carboxlic acid ester having the formula in an aqueous medium in the presence of a protease and reacting the resulting dipeptide ester with the amino carboxylic acid ester and separating the addition compound.The addition compounds can be decomposed into the constituent dipeptide esters and amino acid esters by the action of an acid.
摘要翻译：加成化合物具有式（I）其中R 1表示脂族氧羰基，可具有核取代基的苄氧基羰基或苯甲酰基，芳族磺酰基或芳族亚磺酰基; R 2表示甲基，异丙基，异丁基，异戊基或苄基; R3表示低级烷氧基，苄氧基或二苯甲氧基，n表示1或2.加成化合物通过使具有式（IV）的式（I）所示的N-取代的单氨基二羧酸与式（V）在水性介质中，在蛋白酶存在下，使得到的二肽酯与氨基羧酸酯反应并分离加成化合物。加成化合物可以通过酸的作用分解成组分二肽酯和氨基酸酯。

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