公开(公告)号：EP1057830A1

公开(公告)日：2000-12-06

申请号：EP99906524.6

申请日：1999-02-26

申请人： Eisai Co., Ltd. ,  Yamada, Sumiyo ,  Yamada, Ryoko

发明人： YAMADA, Koji ,  MIYAMOTO, Mitsuaki ,  YOSHIUCHI, Tatsuya ,  SATO, Keizo ,  SOEJIMA, Motohiro ,  SATO, Takashi ,  KIKUCHI, Koichi, Gardenhills Hisamatsu 302 ,  YOSHIMURA, Hiroyuki ,  MORIYA, Katsuhiro ,  SAKUMA, Yoshinori ,  AKASOFU, Shigeru

IPC分类号： C07D513/04 ,  A61K31/54 ,  A61K31/645

CPC分类号： C07D513/04

摘要： The invention provides a novel heterocyclic ring condensed benzothiazine compound which is effective for prevention or remedy of disease, in which histamine, leukotriene and the like participate. The heterocyclic ring condensed benzothiazine compound of the present invention or a pharmacologically acceptable salt thereof is effective for prevention or remedy of disease, in which a chemical mediator, such as histamine, leukotriene and the like, participate, for example, asthma, allergic coryza, atopic dermatitis, hives, hay fever, gastrointestinal allergy, food allergy and the like. Further, the heterocyclic ring condensed benzothiazine compound of the present invention, its pharmacologically acceptable salt or hydrates thereof is represented by the following formula:
In the formula, the ring Het represents an unsaturated heterocyclic ring; R 1 and R 2 are the same as or different from each other, and each represents halogen atom, a lower alkyl group that may be substituted with a halogen atom, a lower alkoxy group that may be substituted with a halogen atom, a lower alkyl lower alkoxy group, cyano group; D represents a lower alkylene group and the like that may have a substituent; Q represents, for example, the formula -NR 20 R 21 (in the formula, R 20 and R 21 are the same as or different from each other, and each represents hydrogen atom, a lower alkyl group that may be substituted with a halogen atom, an aryl group that may have a substituent, an arylalkyl group that may have a substituent, a heteroaryl group that may have a substituent or a heteroarylalkyl group that may have a substituent, or R 20 and R 21 may form a 3- to 8-membered ring along with the nitrogen atom to which they are bound); and x represents an integer of from 1 to 2.

摘要翻译： 本发明提供一种新颖的杂环稠合苯并噻嗪化合物，其对组胺，白细胞三烯等参与的疾病的预防或治疗有效。 本发明的杂环稠合苯并噻嗪化合物或其药理学上可接受的盐对于预防或治疗其中化学介质如组胺，白三烯等参与的疾病是有效的，例如哮喘，过敏性鼻炎， 特应性皮炎，荨麻疹，花粉症，胃肠过敏，食物过敏等。 此外，本发明的杂环稠合苯并噻嗪化合物，其药理学上可接受的盐或其水合物由下式表示：式中，环Het表示不饱和杂环; R 1和R 2彼此相同或不同，各自表示卤素原子，可被卤素原子取代的低级烷基，可被卤素原子取代的低级烷氧基 ，低级烷基低级烷氧基，氰基; D表示可以具有取代基的低级亚烷基等; Q表示例如式-NR 20 R 21（式中，R 20和R 21彼此相同或不同，各自表示氢原子，低级烷基 可以被卤素原子取代的基团，可以具有取代基的芳基，可以具有取代基的芳烷基，可以具有取代基的杂芳基或可以具有取代基的杂芳基烷基，或者R 20 并且R 21可以与它们所结合的氮原子一起形成3至8元环; x表示1〜2的整数。

公开(公告)号：EP0889037A1

公开(公告)日：1999-01-07

申请号：EP97907297.2

申请日：1997-03-13

申请人： Eisai Co., Ltd.

发明人： MIYAMOTO, Mitsuaki ,  YOSHIUCHI, Tatsuya ,  SATO, Keizo ,  KAINO, Makoto ,  TANAKA, Masayuki ,  SOEJIMA, Motoharu ,  MORIYA, Katsuhiro ,  SAKUMA, Yoshinori ,  YAMADA, Koji ,  HARADA, Kokichi ,  NISHIZAWA, Yukio ,  KOBAYASHI, Seiichi ,  OKITA, Makoto ,  KATAYAMA, Koichi

IPC分类号： C07D219/14 ,  C07D243/38 ,  C07D279/24 ,  C07D279/34 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  A61K31/54 ,  A61K31/645

CPC分类号： C07D417/06 ,  C07D279/22 ,  C07D279/24 ,  C07D417/12 ,  C09B21/00 ,  C09B57/08

摘要： To provide a novel phenothiazine, acridan, acridone oxime, acridone hydrazone and dibenzodiazepine derivative efficacious against diseases in which histamine, leukotrienes, etc. participate.
A phenothiazine, acridan, acridone oxime, acridone hydrazone and dibenzodiazepine derivative represented by the following formula are efficacious in preventing or treating diseases in which chemical mediators such as histamine and leukotrienes participate, for example, asthma, allergic rhinitis, atopic dermatitis, urticaria, hay fever, gastrointestinal allergy and food allergy.
A nitrogen-containing tricyclic compound represented by the following formula (I), a hydrate thereof or a pharmacologically acceptable salt thereof:
   (wherein D represents alkylene, etc.)
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are the same or different from each other and each represents hydrogen, hydroxy, cyano, nitro, optionally substituted carbamoyl, halogeno, optionally halogenated lower alkyl, etc.; Z represents -S-, -SO-, -SO 2 -, =NO-substituent, -NC(O)- or =NN-substituent; and Q represents, for example, -NR 20 R 21 (wherein R 20 and R 21 are the same or different from each other and each represents hydrogen, optionally halogenated lower alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl, or R 20 and R 21 may form together with the nitrogen atom to which they are bonded a 3- to 8-membered ring).

摘要翻译： 提供对组胺，白三烯等参与的疾病有效的新型吩噻嗪，吖啶酮，吖啶酮肟，吖啶酮腙和二苯并二氮杂衍生物。 由下式表示的吩噻嗪，吖啶酮，吖啶酮肟，吖啶酮腙和二苯并二氮杂衍生物可有效预防或治疗化学介质如组胺和白三烯参与的疾病，例如哮喘，过敏性鼻炎，特应性皮炎，荨麻疹，干草 发烧，胃肠道过敏和食物过敏。 由下式（I）表示的含氮三环化合物，其水合物或其药理学上可接受的盐：（其中D表示亚烷基等，其中R 1，R 2， R 3，R 4，R 5，R 6，R 7和R 8彼此相同或不同，各自表示氢，羟基，氰基，硝基，任选取代的氨基甲酰基， 卤代，任选卤代的低级烷基等; Z表示-S-，-SO-，-SO 2 - ，= NO-取代基，-NC（O） - 或= N - 取代基; Q表示例如-NR R 20和R 21彼此相同或不同，各自表示氢，任选卤代的低级烷基，任选取代的芳基，任选取代的芳烷基，任选取代的杂芳基或任选取代的 杂芳基烷基或R 20和R 21可以与它们所键合的氮原子一起形成3-至8-元环）。

公开(公告)号：EP1382603A1

公开(公告)日：2004-01-21

申请号：EP02722791.7

申请日：2002-04-25

申请人： Eisai Co., Ltd.

发明人： YOSHIDA, Ichiro ,  YONEDA, Naoki ,  OHASHI, Yoshiaki ,  SUZUKI, Shuichi ,  MIYAMOTO, Mitsuaki ,  MIYAZAKI, Futoshi ,  SESHIMO, Hidenori ,  KAMATA, Junichi ,  TAKASE, Yasutaka ,  SHIRATO, Manabu ,  SHIMOKUBO, Daiya ,  SAKUMA, Yoshinori ,  YOKOHAMA, Hiromitsu

IPC分类号： C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D409/14 ,  C07D413/04 ,  C07D471/04 ,  C07F5/02 ,  A61K31/4155 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/5415 ,  A61K31/551 ,  A61P1/04 ,  A61P3/04 ,  A61P11/00

CPC分类号： C07D401/04 ,  A61K31/4155 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/5415 ,  A61K31/551 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/04 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D493/04 ,  C07F5/025 ,  Y02P20/55

摘要： The present invention provides a compound having an excellent inhibitory action on activation of STAT6 and a pharmaceutical composition thereof. Inparticular, it provides a compound represented by the following formula (I), a salt thereof or a hydrate of them.
In the formula, X represents a nitrogen-containing condensed aromatic heterocyclic group such as imidazo[1,2-a]pyridine, benzimidazole, quinazoline, quinoline, or 2,1-benzisoxazole and has (R 4 ) n as substituent groups; Y represents a C 3-8 cycloalkyl group, C 4-8 cycloalkenyl group, 5- to 14-membered non-aromatic heterocyclic group, C 6-14 aromatic hydrocarbon cyclic group or 5- to 14-membered aromatic heterocyclic group; n in (R 4 ) n is 0, 1, 2 or 3, and Z groups independently represent (1) hydrogen atom, (2) amino group, (3) halogen atom, (4) hydroxyl group, (5) nitro group, (6) cyano group, (7) azido group, (8) formyl group, (9) hydroxyamino group, (10) sulfamoyl group, (11) guanodino group, (12) oxo group, (13) C 2-6 alkenyl group, (14) C 1-6 alkoxy group, (15) C 1-6 alkylhydroxyamino group, (16) halogenated C 1-6 alkyl group, (17) halogenated C 2-6 alkenyl group, (18) (i) C 3-7 cycloalkyl group, (ii) C 3-7 cycloalkenyl group, (iii) 5- to 14-membered non-aromatic heterocyclic group, each of which may have one or more substituent groups Q, or (19) formula -M 1 -M 2 -M 3 , R 1 represents (1) hydrogen atom, (2) halogen atom, (3) hydroxyl group, (4) nitro group, (5) cyano group, (6) halogenated C 1-6 alkyl group, (7) C 2-6 alkyl group substituted with a hydroxyl or cyano group, (8) C 2-6 alkenyl group, or (9) formula -L 1 -L 2 -L 3 , and R 2 represents a hydrogen atom or a protecting group; and R 3 represents a hydrogen atom, halogen atom, cyano group, amino group, C 1-4 alkyl group or halogenated C 1-4 alkyl group.

摘要翻译： 本发明提供具有上STAT6活化优异的抑制作用和它们的药物组合物的化合物。 Inparticular，它提供了由下式（I）表示的化合物，其盐或它们的水合物。 在该式中，X darstellt含氮稠环芳香杂环基团：如imidazoÄ1,2-aÜpyridine，苯并咪唑，喹唑啉，喹啉，或2,1-苯并异恶唑和具有（R <4>）n的取代基; Y表示C 3-8环烷基，C 4-8环烯基，5至14元非芳香族杂环基，C 6-14的芳香族烃环基团或5-至14-元芳族杂环基团; n的（R <4>）n为0，1，2或3，和Z基团独立地代表（1）氢原子，（2）氨基，（3）卤素原子，（4）羟基，（5） 硝基，（6）氰基，（7）叠氮基，（8）甲酰基，（9）羟基，（10）氨磺酰基，（11）鸟粪恐龙基，（12）氧代基团，（13）C 2 -C 6烯基，（14）C1-6烷氧基，（15）C 1-6烷基羟氨基基团，（16）卤代C 1-6烷基，（17）卤代C2-6链烯基，（18）（ⅰ）C3 3-7环基，（ⅱ）C3-7cycloalkenyl基，（ⅲ）5-至14-元非芳族杂环基团，其中的每一个可以具有一个或多个取代基Q，或（19）式-M <1> -M <2> -M <3>，R <1>表示（1）氢原子，（2）卤素原子，（3）羟基，（4）硝基，（5）氰基，（6）卤代的C1 6烷基，（7）C2-6烷基substituiertem用羟基或氰基，（8）C2-6链烯基，或（9）式-L <1> -L <2> -L <3>， 且R <2> darstellt一个氢原子或一个保护基团; 且R <3> darstellt一个氢原子，卤素原子，氰基，氨基，C 1-4烷基或卤代C 1-4烷基。

公开(公告)号：EP0857721A1

公开(公告)日：1998-08-12

申请号：EP96932811.1

申请日：1996-10-03

申请人： Eisai Co., Ltd.

发明人： MIYAMOTO, Mitsuaki ,  YOSHIUCHI, Tatsuya ,  SATO, Keizo ,  KAINO, Makoto ,  TAKASHIMA, Yoshihiro ,  MORIYA, Katsuhiro ,  SAKUMA, Yoshinori ,  YAMADA, Koji ,  HARADA, kOkichi ,  NISHIZAWA, Yukio ,  KOBAYASHI, Seiichi ,  OKITA, Makoto ,  KATAYAMA, Koichi

IPC分类号： C07D219/14 ,  C07D219/06 ,  C07D401/12 ,  C07D405/06 ,  C07D405/12 ,  A61K31/645 ,  A61K31/44 ,  A61K31/47

CPC分类号： C07D219/14

摘要： Novel acridone compounds represented by the general formula (I) or pharmaceutically acceptable salts thereof efficacious in the prevention and treatment of diseases in which chemical transmitters such as histamine and leukotriene participate, typified by asthma, allergic rhinitis, atopic dermatitis, urticaria, hay fever, digestive tract allergy and food allergy:
wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are the same or different and each represents hydrogen, hydroxy, halogeno, lower alkyl, cycloalkyl, lower alkoxy, etc.; Y represents -(CH 2 ) t -(B) m -(CH 2 ) n -Z {wherein m is 0 or 1; t and n represent each an integer of 0 to 6; B represents lower alkylene, optionally substituted arylene, etc.; and Z represents cyano, optionally protected carboxy, acyl, -NR 7 R 8 [wherein R 7 and R 8 are the same or different and each represents hydrogen, lower alkyl, lower alkoxy, hydroxyalkyl, etc.]}; and D represents oxygen or sulfur.

摘要翻译： 由通式（I）表示的新型吖啶酮化合物或其药学上可接受的盐在预防和治疗其中化学传递物质例如组胺和白三烯参与的疾病中有效，所述疾病以哮喘，变应性鼻炎，特应性皮炎，荨麻疹，花粉热， 消化道过敏和食物过敏：其中R1，R2，R3，R4，R5和R6相同或不同，并且各自代表氢，羟基，卤代，低级烷基，环烷基，低级烷氧基等; Y表示 - （CH 2）t - （B）m - （CH 2）n -Z {其中m是0或1; t和n分别表示0〜6的整数。 B代表低级亚烷基，任选取代的亚芳基等; 和Z代表氰基，任选保护的羧基，酰基，-NR7R8 [其中R7和R8相同或不同并且各自代表氢，低级烷基，低级烷氧基，羟基烷基等]}; D代表氧或硫。