公开(公告)号：EP0541798B1

公开(公告)日：1995-11-29

申请号：EP90910895.3

申请日：1990-07-30

申请人： KOWA COMPANY LTD.

发明人： SATO, Seiichi ,  KAWAMURA, Kiyoshi ,  TAKAHASHI, Yoshio ,  WATANABE, Koichiro ,  SHIMIZU, Sadahiro ,  OHTA, Tomio

IPC分类号： C07C211/27 ,  C07C271/28 ,  C07C309/65 ,  C07C327/36 ,  C07D243/08 ,  A61K31/495 ,  A61K31/25 ,  A61K31/27

CPC分类号： C07D295/13 ,  C07C211/27 ,  C07C211/49 ,  C07C237/04 ,  C07C271/28 ,  C07C275/34 ,  C07C311/29 ,  C07C327/30

摘要： Diamine compounds represented by general formula (I) and acid addition salts thereof, and a brain protecting agent containing the same, wherein R1 to R6 may be the same or different from one another and each represents hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy, lower acyloxy, lower alkoxycarbonyloxy, lower alkylsulfonyloxy or amino, among which the lower alkyl and lower alkoxy may be each substituted by halogen or phenyl; R7 and R8 may be the same or different from each other and each represents lower alkyl, or they may be combined together to form alkylene having 1 to 4 carbon atoms; A and A' may be the same or different from each other and each represents a single bond, -O-, -NH-, -NHCO←, -CONH←, -NHCOO←, -NHCONH-, -SONH2← or -COS←, wherein symbol '←' represents a bond to Y or Y'; and Y and Y' may be the same or different from each other and each represents lower alkylene or lower alkenylene. They have an excellent activity of protecting the brain, are highly safe, and can exhibit potent activities by oral administration. Medicines containing them are effecting in treating or preventing the progress of cerebral dysfunctions accompanying cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, transient cerebral ischemic attack, or cerebrovascular diseases.

摘要翻译： 本发明提供式（I）的二胺化合物或其酸加成盐：其中R1，R2，R3，R4，R5和R6彼此相同或不同，并分别表示氢原子，卤素 低级烷氧基，低级烷氧基羰氧基，低级烷基磺酰氧基或氨基，其中低级烷基和低级烷氧基可被卤素原子或苯基取代 ; R 7和R 8彼此相同或不同，分别表示低级烷基或两个彼此结合以表示具有1至4个碳原子的亚烷基; A和A'彼此相同或不同，并分别表示单键，-O - ， - NH - ， - NHCO - ， - CONH - ， - NHCOO - ，NHCONH-，-SO 2 NH-或 -COS->（这里，符号“ - ”表示与Y或Y'的键），Y和Y'彼此相同或不同，表示低级亚烷基或低级亚烯基; 和含有这种化合物的脑保护药。 二胺化合物（I）或其酸加成盐具有优异的脑保护作用，非常安全，甚至在口服给药时也表现出强烈的作用，因此含有这些化合物的药物对于治疗由脑出血引起的疾病有效 梗死，蛛网膜下腔出血，短暂性脑缺血发作，脑血管障碍等，或预防这些疾病的进展。

公开(公告)号：EP0541798A1

公开(公告)日：1993-05-19

申请号：EP90910895.3

申请日：1990-07-30

申请人： KOWA COMPANY LTD.

发明人： SATO, Seiichi ,  KAWAMURA, Kiyoshi ,  TAKAHASHI, Yoshio ,  WATANABE, Koichiro ,  SHIMIZU, Sadahiro ,  OHTA, Tomio

IPC分类号： C07C211/27 ,  C07C271/28 ,  C07C309/65 ,  C07C327/36 ,  C07D243/08 ,  A61K31/495 ,  A61K31/25 ,  A61K31/27

CPC分类号： C07D295/13 ,  C07C211/27 ,  C07C211/49 ,  C07C237/04 ,  C07C271/28 ,  C07C275/34 ,  C07C311/29 ,  C07C327/30

摘要： The present invention provides a diamine compound of formula (I) or an acid addition salt thereof:

wherein R1, R2, R3, R4, R5 and R6 are the same or different from each other and represent individually a hydrogen atom, halogen atom, hydroxyl group, lower alkyl group, lower alkoxy group, lower acyloxy group, lower alkoxycarbonyloxy group, lower alkylsulfonyloxy group or am amino group, among which the lower alkyl group and lower alkoxy group may be substituted by a halogen atom or a phenyl group; R7 and R8 are the same or different from each other and represent individually a lower alkyl group or the two bind to each other to represent an alkylene group having 1 to 4 carbon atoms; A and A' are the same or different from each other and represent individually a single bond, -O-, -NH-, -NHCO→, -CONH→, -NHCOO→, NHCONH-, -SO₂NH→ or -COS→ (here, the symbol '→' denotes a bond to Y or Y'), Y and Y' are the same or different from each other and represent a lower alkylene group or lower alkenylene group; and cerebral protective drugs containing such compound.
The diamine compounds (I) or its acid addition salts have an excellent cerebral protective action, are very safe, and exhibit a strong action when even orally administered, and therefore, medicines containing such compounds are effective for treating disorders caused by cerebral hemorrhage, cerebral infarction, subarachnoid hemorrhage, transient ischemic attack, cerebrovascular disorders and the like, or preventing progress of such disorders.

公开(公告)号：EP0406438B1

公开(公告)日：1994-03-16

申请号：EP90900359.2

申请日：1989-12-25

申请人： KOWA COMPANY LTD.

发明人： KAWAMURA, Kiyoshi ,  OTA, Tomio

IPC分类号： C07D301/28

CPC分类号： C07D303/22 ,  C07D407/12

摘要： This invention relates to a method for producing a glycidyl ether of general formula (I), wherein A is an optionally substituted aryl or heteroaryl group and the asterisked carbon atom represents an asymmetric carbon atom, comprising reacting an aryl alcohol of the general formula A-OH, wherein A is as defined above, with an epihalohydrin in the presence of a quaternary ammonium salt and, if necessary, treating the reaction product with a base. This method can afford the glycidyl ether of formula (I), which is useful as an intermediate of drugs, especially a β-blocker, in a simplified manner with a high optical purity.

公开(公告)号：EP0406438A1

公开(公告)日：1991-01-09

申请号：EP90900359.2

申请日：1989-12-25

申请人： Kowa Company. Ltd.

发明人： KAWAMURA, Kiyoshi ,  OTA, Tomio

IPC分类号： C07D301/28

CPC分类号： C07D303/22 ,  C07D407/12

摘要： This invention relates to a method for producing a glycidyl ether of general formula (I), wherein A is an optionally substituted aryl or heteroaryl group and the asterisked carbon atom represents an asymmetric carbon atom, comprising reacting an aryl alcohol of the general formula A-OH, wherein A is as defined above, with an epihalohydrin in the presence of a quaternary ammonium salt and, if necessary, treating the reaction product with a base. This method can afford the glycidyl ether of formula (I), which is useful as an intermediate of drugs, especially a β-blocker, in a simplified manner with a high optical purity.

摘要翻译： 本发明涉及一种制备通式（I）的缩水甘油醚的方法，其中A是任选取代的芳基或杂芳基，而星号碳原子代表不对称碳原子，包括使通式为A- OH，其中A如上定义，在季铵盐存在下与表卤代醇反应，如果需要，用碱处理反应产物。 该方法可以以简单的方式提供具有高光学纯度的式（I）的缩水甘油醚，其可用作药物的中间体，特别是β-阻滞剂。