公开(公告)号：US4889858A

公开(公告)日：1989-12-26

申请号：US180104

申请日：1988-02-17

申请人： Hitoshi Uno ,  Mikio Kurokawa ,  Fuminori Sato ,  Shunsuke Naruto ,  Yoshinobu Masuda

发明人： Hitoshi Uno ,  Mikio Kurokawa ,  Fuminori Sato ,  Shunsuke Naruto ,  Yoshinobu Masuda

IPC分类号： C07D313/12 ,  C07D401/12 ,  C07D409/12

CPC分类号： C07D401/12 ,  C07D313/12 ,  C07D409/12

摘要： The present invention relates to compounds represented by the general formula (I): ##STR1## wherein R.sub.1 is H or methoxy, R.sub.2 is H, methoxy, OH or F, R.sub.3 is H or F, R.sub.4 is H or F at 7-, 8- or 9-position, and .circle.Ar is a benzene, thiophene or pyridine ring, provided that (i) at least two of R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are H, (ii) R.sub.2 or R.sub.3 is F when R.sub.4 is F, (iii) R.sub.1, R.sub.3 and R.sub.4 are H when R.sub.2 is methoxy or OH, (iv) R.sub.2 and R.sub.3 are not simultaneously F, and (v) R.sub.2 and R.sub.3 are H or F, and both R.sub.1 and R.sub.4 are H when .circle.Ar is a thiophene or pyridine ring, or a physiologically acceptable acid addition salt thereof. The compounds of the present invention have an excellent protective effect against cerebral anoxia and some of them have also an inhibitory effect on lipid peroxidation of mitochondrial membrane of brain and an anti-convulsant activity and are useful as an agent for prevention or treatment of cerebral diseases caused by hypoxia in mammals including human.

公开(公告)号：US4356186A

公开(公告)日：1982-10-26

申请号：US246114

申请日：1981-03-20

申请人： Hitoshi Uno ,  Mikio Kurokawa ,  Hideo Nakamura

发明人： Hitoshi Uno ,  Mikio Kurokawa ,  Hideo Nakamura

IPC分类号： A61K31/34 ,  A61K31/38 ,  A61P29/00 ,  C07D313/12 ,  C07D337/12 ,  C07D337/14 ,  C07D405/06 ,  C07D409/06 ,  A61K31/335

CPC分类号： C07C323/00 ,  C07D313/12 ,  C07D337/12 ,  Y10S514/825 ,  Y10S514/916

摘要： Novel acetic acid derivatives of the formula: ##STR1## wherein X is oxygen or sulfur; R.sub.1 is hydrogen or a lower alkyl; R.sub.2 is hydroxy, an alkoxy, an alkenyloxy, a cycloalkyloxy, an aryloxy, a substituted aryloxy, an aryl-lower alkoxy, a substituted aryl-lower alkoxy, an aryl-lower alkenyloxy, a substituted aryl-lower alkenyloxy, an .omega.-disubstituted amino-lower alkoxy, a lower alkoxycrbonyl-lower alkoxy, a lower alkoxy-lower alkoxy, a hydroxy-lower alkoxy-lower alkoxy, an acyl-lower alkoxy, or a group ##STR2## wherein R.sub.3 is hydrogen, hydroxy, a lower alkyl, an aryl-lower alkyl, a hydroxy-lower alkyl, or a carboxy-lower alkyl, R.sub.4 is hydrogen, a lower alkyl or a hydroxy-lower alkyl, or the R.sub.3 and R.sub.4 may combine together with the nitrogen atom to which they are joined to form a heterocyclic group; and the group --CH(R.sub.1)COR.sub.2 is joined to the carbon atom at 2- or 3-position, and pharmaceutically acceptable salts thereof, processes for their preparation, and pharmaceutical compositions containing these compounds. They have excellent anti-inflammatory, analgesic and antipyretic activities with weak ulcerogenicity in the gastrointestinal tract and toxicity.

摘要翻译： 下式的新型乙酸衍生物：其中X是氧或硫; R1是氢或低级烷基; R2是羟基，烷氧基，烯氧基，环烷氧基，芳氧基，取代的芳氧基，芳基 - 低级烷氧基，取代的芳基 - 低级烷氧基，芳基 - 低级烯氧基，取代的芳基 - 低级烯氧基，ω-二取代 氨基 - 低级烷氧基，低级烷氧基羰基 - 低级烷氧基，低级烷氧基 - 低级烷氧基，羟基 - 低级烷氧基 - 低级烷氧基，酰基 - 低级烷氧基或基团，其中R3是氢，羟基，低级烷基 ，芳基 - 低级烷基，羟基 - 低级烷基或羧基 - 低级烷基，R 4是氢，低级烷基或羟基 - 低级烷基，或者R 3和R 4可以与它们所在的氮原子结合在一起 连接形成杂环基; 并且基团-CH（R 1）COR 2与2-或3-位的碳原子及其药学上可接受的盐连接，其制备方法和含有这些化合物的药物组合物。 它们具有优良的抗炎，止痛和解热活性，肠胃道溃疡性弱，毒性低。

公开(公告)号：US3948928A

公开(公告)日：1976-04-06

申请号：US340195

申请日：1973-03-12

申请人： Haruki Nishimura ,  Masanao Shimizu ,  Hitoshi Uno ,  Tetsuo Hirooka ,  Yoshinobu Masuda ,  Mikio Kurokawa

发明人： Haruki Nishimura ,  Masanao Shimizu ,  Hitoshi Uno ,  Tetsuo Hirooka ,  Yoshinobu Masuda ,  Mikio Kurokawa

IPC分类号： A61K31/42 ,  C07D261/20

CPC分类号： A61K31/42 ,  C07D261/20

摘要： 3-Substituted-1,2-benzisoxazole derivative of the following formula: ##SPC1##Wherein R.sub.1 is hydrogen, hydroxy, nitro, alkyl, alkoxy, halogen or amino; R.sub.2 is hydroxyamino, amino, hydrazino, mono- or di- alkyl substituted amino, aralkylamino, acyloxyamino, morpholino, piperazine which is unsubstituted or substituted with alkyl, aralkyl or aryl at 4 position, or pyrrolidino, or R.sub.2 may combine with imino group and form together with the adjacent carbon atom a heterocyclic ring such as imidazoline or tetrahydropyrimidine; and n is an integer of 0 to 3, and its pharmaceutically acceptable acid addition salt, and preparation thereof. The present compounds show valuable pharmacological properties, such as anti-reserpine activity, central nervous depressing activity, anti-hypertensive activity and l-dopa potentiating activity.

摘要翻译： 3-取代的1,2-苯并异恶唑衍生物：

公开(公告)号：US5128354A

公开(公告)日：1992-07-07

申请号：US499444

申请日：1990-06-25

申请人： Yoshinobu Masuda ,  Toshiaki Kadokawa ,  Mikio Kurokawa ,  Kayoko Zushi ,  Yoshiaki Ochi

发明人： Yoshinobu Masuda ,  Toshiaki Kadokawa ,  Mikio Kurokawa ,  Kayoko Zushi ,  Yoshiaki Ochi

IPC分类号： A61K31/42 ,  C07D261/20

CPC分类号： A61K31/42 ,  C07D261/20

摘要： The present invention provides an agent for treating ischemic brain damage comprising 3-sulfamoylmethyl-1,2-benzisoxazole or its alkali metal salt as an active ingredient. This agent can be used for the prevention and/or treatment of cerebral ischemia-induced intracranial diseases or various symptoms associated therewith in mammals including human beings.

公开(公告)号：US4749703A

公开(公告)日：1988-06-07

申请号：US855849

申请日：1986-04-10

申请人： Hitoshi Uno ,  Mikio Kurokawa ,  Fuminori Sato ,  Naonobu Hatano

发明人： Hitoshi Uno ,  Mikio Kurokawa ,  Fuminori Sato ,  Naonobu Hatano

IPC分类号： C07D311/88 ,  A61K31/00 ,  A61K31/435 ,  A61K31/495 ,  A61K31/55 ,  A61P3/00 ,  A61P9/00 ,  A61P9/10 ,  A61P9/12 ,  C07D213/74 ,  C07D215/38 ,  C07D219/10 ,  C07D239/42 ,  C07D243/00 ,  C07D277/38 ,  C07D295/14 ,  C07D295/15 ,  C07D313/12 ,  C07D335/18 ,  C07D337/00 ,  C07D337/12 ,  C07D401/04 ,  C07D409/12 ,  A61K31/38 ,  C07D241/02

CPC分类号： C07D215/38 ,  C07D213/74 ,  C07D239/42 ,  C07D277/38 ,  C07D295/15 ,  C07D337/12 ,  C07D409/12

摘要： Compounds of the formula: ##STR1## wherein A means an alkylene; Y--Z means ##STR2## --CH.dbd.CH--, --CH.sub.2 CH.sub.2 --, or ##STR3## R.sub.1 and R.sub.2 are each a substituent; R.sub.3 is hydrogen atom, alkyl, or alkoxy; R.sub.4 is phenyl, phenylalkyl, phenylalkenyl, diphenylmethyl, naphthyl, thiazolyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, quinolyl, benzoylalkyl, benzoyl, furoyl, thenoyl, phenyloxycarbonyl, phenyloxysulfonyl, or phenylsulfonyl; a is 2 or 3, b and c are each 1 or 2, and d is an integer of 0 to 2, provided that the phenyl, phenyl moiety and naphthyl may optionally be substituted, and a pharmaceutically acceptable salt thereof, process for the preparation thereof, and pharmaceutical composition containing the same. The compounds and salt thereof show potent calcium antagonistic activity and are useful for prophylaxis and treatment of hypertension and/or ischemic heart disease.

摘要翻译： PCT No.PCT / JP85 / 00445 Sec。 一九八六年四月十日 102（e）日期1986年4月10日PCT提交1985年8月9日PCT公布。 公开号WO86 / 01203 日期：1986年2月27日。下式的化合物：其中A表示亚烷基; Y-Z表示 -CH = CH-，-CH2CH2-或R1，R2和R2各自为取代基; R3是氢原子，烷基或烷氧基; R4是苯基，苯基烷基，苯基链烯基，二苯甲基，萘基，噻唑基，任选取代的吡啶基，任选取代的嘧啶基，喹啉基，苯甲酰基烷基，苯甲酰基，糠酰基，噻吩甲酰基，苯氧基羰基，苯氧基磺酰基或苯基磺酰基; a为2或3，b和c各自为1或2，d为0至2的整数，条件是苯基，苯基部分和萘基可任选被取代，及其药学上可接受的盐，其制备方法 及含有该组合物的药物组合物。 化合物及其盐显示出有效的钙拮抗活性，可用于预防和治疗高血压和/或缺血性心脏病。

公开(公告)号：US4172896A

公开(公告)日：1979-10-30

申请号：US912857

申请日：1978-06-05

申请人： Hitoshi Uno ,  Mikio Kurokawa ,  Yoshinobu Masuda

发明人： Hitoshi Uno ,  Mikio Kurokawa ,  Yoshinobu Masuda

IPC分类号： C07D261/20 ,  C07D263/56 ,  A61K31/42

CPC分类号： C07D263/56 ,  C07D261/20

摘要： Methane-sulfonamide derivatives of the formula: ##STR1## wherein R.sub.1 is hydrogen or a halogen atom, R.sub.2 and R.sub.3 are the same or different and are each hydrogen or a straight or branched alkyl having 1 to 3 carbon atoms, and one of X and Y is a carbon atom and another is a nitrogen atom, provided that the group: --CH.sub.2 SO.sub.2 NR.sub.2 R.sub.3 is bonded to the carbon atom of either of X and Y,and an alkali metal salt thereof, and a process for the preparation of said methane-sulfonamide derivatives. Said compounds have an excellent anticonvulsant activity and are useful as anticonvulsants for controlling convulsions and seizures in patients with epilepsy.

摘要翻译： 下式的甲磺酰胺衍生物：其中R 1是氢或卤素原子，R 2和R 3相同或不同，各自为氢或具有1至3个碳原子的直链或支链烷基， 的X和Y是碳原子，另一个是氮原子，条件是：-CH 2 SO 2 NR 2 R 3基团与X和Y中的任一个的碳原子键合，及其碱金属盐，以及制备所述 甲磺酰胺衍生物。 所述化合物具有优异的抗惊厥活性，可用作控制癫痫患者惊厥和癫痫发作的抗惊厥药。