公开(公告)号：US4550076A

公开(公告)日：1985-10-29

申请号：US424182

申请日：1982-09-27

申请人： Nobumoto Chikazawa ,  Toshiharu Muraoka ,  Setsuro Fujii

发明人： Nobumoto Chikazawa ,  Toshiharu Muraoka ,  Setsuro Fujii

IPC分类号： C12Q1/26 ,  C12Q1/28 ,  C12Q1/34

CPC分类号： C12Q1/28 ,  C12Q1/34 ,  G01N2333/978

摘要： The guanase activity in body fluids such as blood serum can be rapidly and accurately assayed by (I) decomposing guanine with the guanase in the specimen to xanthine and ammonia at pH 7-9, preferably at pH 8, (II) decomposing the xanthine formed by former step I with xanthine oxidase to uric acid and hydrogen peroxide, (III) reacting the reactant solution of the former step II with 3-methyl-2-benzothiazolinonehydrazone, an aniline derivative such as N,N-di-lower-alkylaniline and peroxidase, and finally measuring the optical absorption of the reactant solution of the step III at 570-600 nm. The all steps can be completed within 15 minutes. Therefore, this assay is adoptable for automatic assay of guanase on usual clinically available automatic analyzers.

摘要翻译： 通过（I）将样品中的鸟嘌呤分解为黄嘌呤和氨，pH7-9，优选pH8，（II）分解形成的黄嘌呤的鸟嘌呤，可快速准确地测定体液如血清中的鸟苷酸活性 通过前一步骤I将黄嘌呤氧化酶与尿酸和过氧化氢反应，（III）使前一步骤II的反应物溶液与3-甲基-2-苯并噻唑酮腙，苯胺衍生物如N，N-二低级烷基苯胺和 过氧化物酶，最后在570-600nm测量步骤III的反应物溶液的光吸收。 所有步骤可在15分钟内完成。 因此，该测定法可用于通常临床可用的自动分析仪上的鸟苷酸的自动测定。

公开(公告)号：US4503045A

公开(公告)日：1985-03-05

申请号：US234569

申请日：1981-02-13

申请人： Setsuro Fujii ,  Bompei Yasui ,  Tomohisa Miyamoto ,  Masatoshi Shiga ,  Kazuko Ando ,  Iwao Hashimoto ,  Masahiro Kawasaki ,  Yoichiro Kawai ,  Yuji Mino

发明人： Setsuro Fujii ,  Bompei Yasui ,  Tomohisa Miyamoto ,  Masatoshi Shiga ,  Kazuko Ando ,  Iwao Hashimoto ,  Masahiro Kawasaki ,  Yoichiro Kawai ,  Yuji Mino

IPC分类号： C07H19/073 ,  A61K31/70 ,  A61K31/7042 ,  A61K31/7052 ,  A61K31/7064 ,  A61K31/7072 ,  A61P35/00 ,  C07H19/00 ,  C07H19/06 ,  C07H19/08

CPC分类号： C07H19/06

摘要： 2'-Deoxy-3',5'-di-O-alkylcarbonyl-5-fluorouridine derivatives possessing strong anti-tumor activity with weak toxicity and represented by the general formula: ##STR1## wherein R stands for an alkyl group, an alkoxy group or a halogen atom, m for zero or an integer of 1-3, and n for an integer of 1-14, with the proviso that when m is 2 or 3, R's may be the same or different and that when m is 2 and the adjacent two R's are alkoxy groups, the two alkyl moieties of the alkoxy groups may be combined to form together with the two adjacent oxa bridging members an alkylenedioxy group as a whole. These derivatives are prepared by acylating a 2'-deoxy-3',5'-di-O-alkylcarbonyl-5-fluorouridine with corresponding benzoyl halides and are useful as active ingredients for anti-tumor agents, especially for oral administration.

摘要翻译： 2'-脱氧-3'，5'-二-O-烷基羰基-5-氟尿苷衍生物具有强的抗肿瘤活性，毒性弱，由以下通式表示：其中R代表烷基，烷氧基 基团或卤素原子，m为0或1-3的整数，n为1-14的整数，条件是当m为2或3时，R可以相同或不同，当m为 2并且相邻的两个R是烷氧基，烷氧基的两个烷基部分可以与两个相邻的氧杂桥连成员一起与亚烷基二氧基整体形成。 这些衍生物通过用相应的苯甲酰卤酰化2'-脱氧-3'，5'-二-O-烷基羰基-5-氟尿苷来制备，并且可用作抗肿瘤剂的活性成分，特别是用于口服给药。

公开(公告)号：US4496584A

公开(公告)日：1985-01-29

申请号：US370647

申请日：1982-04-21

申请人： Setsuro Fujii ,  Takashi Yaegashi ,  Toyoo Nakayama ,  Shigeki Nunomura ,  Yojiro Sakurai ,  Toshiyuki Okutome

发明人： Setsuro Fujii ,  Takashi Yaegashi ,  Toyoo Nakayama ,  Shigeki Nunomura ,  Yojiro Sakurai ,  Toshiyuki Okutome

IPC分类号： A61K31/215 ,  A61K31/155 ,  A61K31/22 ,  A61K31/23 ,  A61K31/27 ,  A61P1/00 ,  A61P7/00 ,  A61P13/02 ,  A61P15/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07C67/00 ,  C07C69/035 ,  C07C239/00 ,  C07C257/18 ,  C07C279/14 ,  C11C3/04

CPC分类号： C07C257/18

摘要： Amidino compounds represented by the formula ##STR1## and pharmaceutically acceptable acid addition salts thereof are novel compounds and are useful as powerful antitrypsin, antiplasmin, antikallikrein and antithrombin agents. Having strong anti-Cl activity and anti-complement activity, they are also useful as anti-complement agents. These amidino compounds are prepared by reacting carboxylic compounds represented by the formulaR.sub.1 --COOHor their reactive intermediates with amidinonaphthol represented by the formula ##STR2## and, if necessary, can be transformed into pharmaceutically acceptable acid addition salts thereof.

摘要翻译： 由式＆lt; IMAGE＆gt;表示的脒基化合物及其药学上可接受的酸加成盐是新的化合物，可用作强抗胰蛋白酶，抗血浆素，抗激肽释放酶和抗凝血酶剂。 具有强的抗C1活性和抗补体活性，它们也可用作抗补体剂。 这些脒基化合物通过使由式R 1 -COOH表示的羧酸化合物或其反应性中间体与由式“IMAGE”表示的脒基萘酚反应并且如果需要可以转化成其药学上可接受的酸加成盐来制备。

公开(公告)号：US4490388A

公开(公告)日：1984-12-25

申请号：US350964

申请日：1982-02-22

申请人： Setsuro Fujii ,  Takuo Aoyama ,  Yojiro Sakurai ,  Toyoo Nakayama ,  Shigeki Nunomura ,  Takashi Yaegashi ,  Toshiyuki Okutome

发明人： Setsuro Fujii ,  Takuo Aoyama ,  Yojiro Sakurai ,  Toyoo Nakayama ,  Shigeki Nunomura ,  Takashi Yaegashi ,  Toshiyuki Okutome

IPC分类号： C07C271/22 ,  C07C279/18 ,  C07D317/60 ,  C07D317/68 ,  C07C101/00 ,  A61K31/215

CPC分类号： C07D317/68 ,  C07C271/22 ,  C07C279/18 ,  C07D317/60

摘要： Amidino compounds represented by the formula (I) ##STR1## and pharmaceutically acceptable acid addition salts thereof are novel compounds and are useful as powerful antitrypsine, antiplasmin, antikallikrein and anti-thrombin agents. Having strong anti-Cl (Clr, Cls) activities and an anticomplement activity, they are also useful as anticomplement agents. These amidino compounds are prepared by usual esterification of carboxylic acid compounds represented by the formula (II)R.sub.1 --COOH (II)with 4-(.beta.-amidinoethenyl)phenol represented by the formula (III) ##STR2## and, if necessary, can be transformed into pharmaceutically acceptable acid addition salts thereof.

摘要翻译： 由式（I）表示的脒基化合物及其药学上可接受的酸加成盐是新的化合物，可用作强效的抗胰蛋白酶，抗血纤维蛋白酶，抗激肽释放酶和抗凝血酶剂。 具有强大的抗Cl（Cl＆upbar＆r，Cl＆upbar＆s）活性和抗补体活性，它们也可用作抗补体剂。 这些脒基化合物通过由式（II）R1-COOH（II）表示的羧酸化合物与由式（III）表示的4-（β-脒基乙烯基）苯酚（III）进行常规酯化而制备，如果 必需的，可以转化成其药学上可接受的酸加成盐。

公开(公告)号：US4454338A

公开(公告)日：1984-06-12

申请号：US300534

申请日：1981-09-09

申请人： Setsuro Fujii ,  Toshiyuki Okutome ,  Toyoo Nakayama ,  Takashi Yaegashi ,  Masateru Kurumi

发明人： Setsuro Fujii ,  Toshiyuki Okutome ,  Toyoo Nakayama ,  Takashi Yaegashi ,  Masateru Kurumi

IPC分类号： C07C249/02 ,  A61K31/155 ,  C07C257/18 ,  C07C279/18 ,  C07D317/68 ,  C07C101/00 ,  C07C101/48

CPC分类号： C07D317/68 ,  C07C279/18

摘要： Amidino compounds represented by the formula ##STR1## and pharmaceutically acceptable acid addition salts thereof are novel compounds and are useful as powerful antitrypsine, antiplasmin, antikallikrein and antithrombin agents. Having strong anti-C1 (C1r, C1s) activities and an anticomplement activity, they are also useful as anticomplement agents. These amidino compounds are prepared by usual esterification of carboxylic acid compounds represented by the formula ##STR2## with 6-amidino-2-naphthol and, if necessary, can be transformed into pharmaceuticlly acceptable acid addition salts thereof.

摘要翻译： 由式＆lt; IMAGE＆gt;表示的脒基化合物及其药学上可接受的酸加成盐是新的化合物，可用作强效的抗胰蛋白胨，抗血浆素，抗激肽释放酶和抗凝血酶剂。 具有强大的抗C1（C1＆upbar＆r，C1＆upbar＆s）活性和抗补体活性，它们也可用作抗补体剂。 这些脒基化合物通过将式（ⅩⅧ）代表的羧酸化合物与6-脒基-2-萘酚进行常规的酯化反应来制备，如果需要，可以将其转化成其药学上可接受的酸加成盐。

公开(公告)号：US4425335A

公开(公告)日：1984-01-10

申请号：US291809

申请日：1981-08-10

申请人： Setsuro Fujii ,  Bompei Yasui ,  Mitsuo Nakamura ,  Mitsuru Hirohashi ,  Tomohisa Miyamoto ,  Kazuko Ando ,  Iwao Hashimoto ,  Naoki Umeda ,  Masahiro Kawasaki

发明人： Setsuro Fujii ,  Bompei Yasui ,  Mitsuo Nakamura ,  Mitsuru Hirohashi ,  Tomohisa Miyamoto ,  Kazuko Ando ,  Iwao Hashimoto ,  Naoki Umeda ,  Masahiro Kawasaki

IPC分类号： C07H19/073 ,  A61K31/70 ,  A61K31/7042 ,  A61K31/7052 ,  A61K31/7064 ,  A61K31/7072 ,  A61P35/00 ,  C07H19/06 ,  C07H19/08

CPC分类号： C07H19/06

摘要： New ester derivatives of alkoxybenzoyldeoxyfluorouridine of the general formula ##STR1## wherein R stands for an alkoxy group having 1 to 4 carbon atoms, m for 1 or 2, and n for 3 or 4 with the proviso that when m is 2, the adjacent two R's may be combined to form an alkylenedioxy group as a whole. These derivatives are prepared by acylating a 2'-deoxy-3',5'-di-O-alkylcarbonyl-5-fluorouridine with corresponding benzoyl halides and are useful as active ingredients for anti-tumor agents, especially for oral administration.

摘要翻译： 通式为“IMAGE”的烷氧基苯甲酰基脱氧氟尿酸的新酯衍生物，其中R代表具有1至4个碳原子的烷氧基，m为1或2，n为3或4，条件是当m为2时， R可以组合形成亚烷基二氧基整体。 这些衍生物通过用相应的苯甲酰卤酰化2'-脱氧-3'，5'-二-O-烷基羰基-5-氟尿苷来制备，并且可用作抗肿瘤剂的活性成分，特别是用于口服给药。

公开(公告)号：US4283418A

公开(公告)日：1981-08-11

申请号：US123609

申请日：1980-02-22

申请人： Setsuro Fujii ,  Tsuyoshi Watanabe ,  Masashi Shiota ,  Itsuo Okumoto ,  Naohiro Kayama

发明人： Setsuro Fujii ,  Tsuyoshi Watanabe ,  Masashi Shiota ,  Itsuo Okumoto ,  Naohiro Kayama

IPC分类号： A61K31/155 ,  A61K31/165 ,  A61K31/18 ,  A61K31/24 ,  A61K31/245 ,  C07C101/56

CPC分类号： A61K31/155 ,  A61K31/165 ,  A61K31/18 ,  A61K31/24 ,  A61K31/245

摘要： Guanidinobenzoic acid derivatives represented by the general formula [I] ##STR1## wherein R.sup.1, R.sup.2 and Z are as defined hereinafter, having antiplasmin and anti-trypsin activities and process for their preparation as well as a pharmaceutical composition and a method of inhibiting the activity of plasmin and trypsin is disclosed.

摘要翻译： 由通式[I]表示的胍基苯甲酸衍生物其中R1，R2和Z如下文所定义，具有抗血浆素和抗胰蛋白酶活性及其制备方法以及药物组合物和方法 公开了抑制纤溶酶和胰蛋白酶的活性。

公开(公告)号：US4124765A

公开(公告)日：1978-11-07

申请号：US727422

申请日：1976-09-28

申请人： Masayasu Kurono ,  Takeshi Chiba ,  Setsuro Fujii

发明人： Masayasu Kurono ,  Takeshi Chiba ,  Setsuro Fujii

IPC分类号： C07D239/54 ,  C07D239/553

CPC分类号： C07D239/553

摘要： 5-Fluorouracil derivatives and a process for their preparation are provided. The 5-fluorouracil derivatives according to the invention have the general formula: ##STR1## R.sub.1 and R.sub.2 are the same or different and are hydrogen or ##STR2## with the proviso that both R.sub.1 and R.sub.2 are not hydrogen at the same time. A.sub.1, A.sub.2 and A.sub.3 are independently selected from hydrogen, and optionally substituted alkoxy and phenyloxy; at least one of A.sub.1, A.sub.2 and A.sub.3 being other than hydrogen. The 5-fluorouracil derivative is prepared by condensing 5-fluorouracil with a halide of the formula: ##STR3## in the presence of a base. The 5-fluorouracils according to the invention show anti-tumor activity.

摘要翻译： 提供5-氟尿嘧啶衍生物及其制备方法。 根据本发明的5-氟尿嘧啶衍生物具有以下通式：其中R 1和R 2相同或不同，为氢或“IMAGE”，条件是R 1和R 2不同时为氢。 A1，A2和A3独立地选自氢和任选取代的烷氧基和苯氧基; A1，A2和A3中的至少一个不是氢。 5-氟尿嘧啶衍生物通过在碱存在下将5-氟尿嘧啶与下式的卤化物缩合制备。 根据本发明的5-氟尿嘧啶显示抗肿瘤活性。

公开(公告)号：US5155113A

公开(公告)日：1992-10-13

申请号：US437315

申请日：1989-11-17

申请人： Setsuro Fujii

发明人： Setsuro Fujii

IPC分类号： A61K31/505 ,  C07D213/69 ,  C07D213/80 ,  C07D213/85 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07F7/18 ,  C07H19/06

CPC分类号： C07D213/69 ,  A61K31/505 ,  C07D213/80 ,  C07D213/85 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07F7/1856 ,  C07H19/06

摘要： A composition for increasing the anti-cancer activity of an anti-cancer compound selected from among 5-fluorouracil and a compound capable of producing 5-fluorouracil in vivo, the composition comprising an effective amount of a pyridine derivative represented by the formula ##STR1## wherein R.sup.1 is hydroxy or acyloxy, R.sup.2 and R.sup.4 are each hydrogen, halogen, amino, carboxyl, carbamoyl, cyano, nitro, lower alkyl, lower alkenyl or lower alkoxycarbonyl, R.sup.3 and R.sup.5 are each hydrogen, hydroxy or acyloxy; when at least one or R.sup.1, R.sup.3 and R.sup.5 is hydroxy, the structure of 1-position on the pyridine ring can be ##STR2## due to the keto-enol tautomerism, said hydrogen attached to nitrogen being optionally substituted with a substituent selected from the group consisting of lower alkyl, tetrahydrofuranyl, tetrahydropyranyl, lower alkoxy-lower alkyl, phthalidyl, carbamoyl, lower alkoxycarbonyl-lower alkylcarbamoyl, phenyl-lower alkoxy-lower alkyl, phenylcarbamoyl which may have a substituent on the phenyl ring, lower alkylcarbamoyl, carboxy-lower alkylcarbamoyl, lower alkylthio-lower alkyl and lower alkenyl, provided that the compound having the following formula is excluded, ##STR3## wherein .alpha. is hydrogen, lower alkyl, tetrahydrofuranyl, tetrahydropyranyl, lower alkoxy-lower alkyl, lower alkylcarbamoyl, lower alkylthio-lower alkyl or lower alkenyl.

摘要翻译： 一种用于增加选自5-氟尿嘧啶和能够在体内产生5-氟尿嘧啶的化合物的抗癌化合物的抗癌活性的组合物，该组合物包含有效量的由式表示的吡啶衍生物， （1）其中R1是羟基或酰氧基，R2和R4各自为氢，卤素，氨基，羧基，氨基甲酰基，氰基，硝基，低级烷基，低级烯基或低级烷氧基羰基，R3和R5分别为氢，羟基或酰氧基; 当至少一个或R 1，R 3和R 5为羟基时，由于酮 - 烯醇互变异构，吡啶环上的1-位的结构可以是“IMAGE”，所述与氮连接的氢任选被选自以下的取代基取代： 低级烷基，四氢呋喃基，四氢吡喃基，低级烷氧基 - 低级烷基，邻苯二甲酰基，氨基甲酰基，低级烷氧基羰基 - 低级烷基氨基甲酰基，苯基 - 低级烷氧基 - 低级烷基，苯基上可具有取代基的苯基氨基甲酰基，低级烷基氨基甲酰基， 低级烷基氨基甲酰基，低级烷基氨基甲酰基，低级烷基氨基甲酰基，低级烷基氨基甲酰基，低级烷基氨基甲酰基，低级烷基氨基甲酰基，低级烷基氨基甲酰基，低级烷基氨基甲酰基，低级烷基氨基甲酰基，低级烷基氨基甲酰基， 低级烷基或低级烯基。

公开(公告)号：US4898876A

公开(公告)日：1990-02-06

申请号：US796525

申请日：1985-11-12

申请人： Setsuro Fujii ,  Eizou Hattori ,  Mitsuteru Hirata ,  Koichiro Watanabe ,  Kazuhiro Onogi ,  Masahiko Nagakura

发明人： Setsuro Fujii ,  Eizou Hattori ,  Mitsuteru Hirata ,  Koichiro Watanabe ,  Kazuhiro Onogi ,  Masahiko Nagakura

IPC分类号： C07D209/48 ,  C07D215/48 ,  C07D215/50 ,  C07D215/54 ,  C07D217/26 ,  C07D237/28 ,  C07D241/44 ,  C07D261/18 ,  C07D295/192 ,  C07D307/79 ,  C07D307/84 ,  C07D307/86 ,  C07D311/12 ,  C07D311/58 ,  C07D311/84 ,  C07D317/68 ,  C07D319/18 ,  C07D333/54 ,  C07D333/60

CPC分类号： C07D209/48 ,  C07D215/48 ,  C07D215/50 ,  C07D215/54 ,  C07D217/26 ,  C07D237/28 ,  C07D241/44 ,  C07D261/18 ,  C07D295/192 ,  C07D307/79 ,  C07D307/84 ,  C07D307/86 ,  C07D311/12 ,  C07D311/58 ,  C07D311/84 ,  C07D317/68 ,  C07D319/18 ,  C07D333/54 ,  C07D333/60

摘要： A benzopylpiperazine ester of the following formula: ##STR1## wherein A represents a single bond or an alkylene group, vinylene group, --O--alkylene group or methine group, R.sub.1 represents a bicyclic carbon ring residue which may be substituted with a lower alkyl group, lower alkoxy group, oxo group or nitro group or a halogen atom, or may be partially saturated; a fluorene residue which may contain an oxo group; a fluorenylidene group; an anthracene residue; a phenanthrene residue which may be substituted with a lower alkyl group, or may be partially saturated; a benzofuran residue or thianaphthene residue which may be substituted with a lower alkyl group or lower alkoxy group; a benzopyran residue or benzoazine residue which may be substituted with an oxo group or phenyl group and partially saturated; a phthalimide residue; a benzodiazine residue; an isozazole residue which may be substituted with a lower alkyl group or phenyl group; or an alkylene dioxybenzene residue or xanthene residue; and R.sub.2 represents an alkyl group, cycloalkyl group, cycloalkylalkyl group or aralkyl group, excepting the case where A is a single bond, R.sub.1 is ##STR2## and R.sub.2 is a methyl group, exhibits excellent chymotrypsin inhibitive activity.

摘要翻译： 下式的苯甲酰基哌嗪酯：其中A表示单键或亚烷基，亚乙烯基，-O-亚烷基或次甲基，R 1表示可被低级烷基取代的双环碳环残基 ，低级烷氧基，氧代基或硝基或卤素原子，或可部分饱和; 可含有氧代基的芴残基; 亚芴基; 蒽残基; 可以被低级烷基取代的菲残基，或可以部分饱和; 可以被低级烷基或低级烷氧基取代的苯并呋喃残基或硫杂残基; 可被氧代基或苯基取代并部分饱和的苯并吡喃残基或苯并嗪残基; 邻苯二甲酰亚胺残基; 苯并二氮残基; 可以被低级烷基或苯基取代的异唑残基; 或亚烷基二氧基苯残基或呫吨残基; 除了A为单键，R 1为甲基，R 2为甲基的情况外，R 2表示烷基，环烷基，环烷基烷基或芳烷基，表现出优异的糜蛋白酶抑制活性。