公开(公告)号：EP0719779A1

公开(公告)日：1996-07-03

申请号：EP95921127.7

申请日：1995-06-07

申请人： Eisai Co., Ltd.

发明人： OINUMA, Hitoshi ,  SUDA, Shinji ,  YONEDA, Naoki Tsukubasakuradanchi 906-306 ,  KOTAKE, Makoto ,  MIZUNO, Masanori ,  MATSUSHIMA, Tomohiro ,  FUKUDA, Yoshio ,  SAITO, Mamoru ,  MATSUOKA, Toshiyuki ,  ADACHI, Hideyuki ,  NAMIKI, Masayuki ,  SUDO, Takeshi ,  MIYAKE, Kazutoshi ,  OKITA, Makoto

IPC分类号： C07D513/04 ,  C07D277/06 ,  C07D211/60 ,  A61K31/425

CPC分类号： C07D513/04 ,  A61K38/00 ,  C07K5/06139 ,  Y02P20/55

摘要： The present invention relates to a substituted thiazolo[3,2-a]azepine derivative having inhibitory activity against angiotensin I converting enzyme and neutral endpeptidase.
The above substituted thiazolo[3,2-a]azepine derivative is represented by the following general formula (I):

   (wherein R1 represents a hydrogen atom or a protecting group of a thiol group; R2 represents a hydrogen atom, a lower alkyl group, an aryl group which may have a substituent, a hetroaryl group which may have a substituent, a lower alkoxyl group or a lower alkylthio group; R3, R4 and R5 may be the same or different from one another and represent each a hydrogen atom, a lower alkyl group, a lower alkoxyl group, a lower alkylthio group or the like, with the proviso that the case wherein all of R3, R4 and R5 are hydrogen atoms are excepted;
   R6 and R7 may be the same or different from each other and represent each a hydrogen atom or a lower alkyl group; R8 represents a hydrogen atom or a protecting group of a carboxyl group; and
   m and m are each independently 0 or, 1 or 2).

摘要翻译： 本发明涉及对血管紧张素I转换酶和中性内肽酶具有抑制活性的取代噻唑并[3,2-a]氮杂衍生物。 上述取代的噻唑并[3,2-a]吖庚因衍生物由以下通式（I）表示：（其中R1表示氢原子或硫醇基的保护基; R2表示氢原子，低级烷基， 可以具有取代基的芳基，可以具有取代基的杂芳基，低级烷氧基或低级烷硫基; R3，R4和R5可以相同或不同，表示氢原子， 低级烷基，低级烷氧基，低级烷硫基等，条件是其中R3，R4和R5全部为氢原子的情况除外; R6和R7可以相同或不同， 表示氢原子或低级烷基; R8表示氢原子或羧基的保护基; m和m各自独立地为0或1或2）。

公开(公告)号：EP1394152A1

公开(公告)日：2004-03-03

申请号：EP02720536.8

申请日：2002-04-19

申请人： Eisai Co., Ltd.

发明人： SUZUKI, Shuichi ,  KOTAKE, Makoto ,  MIYAMOTO, Mitsuaki ,  KAWAHARA, Tetsuya ,  KAJIWARA, Akiharu ,  HISHINUMA, Ieharu ,  OKANO, Kazuo ,  MIYAZAWA, Syuhei ,  CLARK, Richard ,  OZAKI, Fumihiro ,  SATO, Nobuaki ,  SHINODA, Masanobu ,  KAMADA, Atsushi ,  TSUKADA, Itaru ,  MATSUURA, Fumiyoshi ,  NAOE, Yoshimitsu ,  TERAUCHI, Taro ,  OOHASHI, Yoshiaki ,  ITO, Osamu ,  TANAKA, Hiroshi ,  MUSYA, Takashi ,  KOGUSHI, Motoji ,  KAWADA, Tsutomu ,  MATSUOKA, Toshiyuki ,  KOBAYASHI, Hiroko ,  CHIBA, Ken-ichi ,  KIMURA, Akifumi ,  ONO, Naoto

IPC分类号： C07D235/30 ,  A61K31/4184 ,  A61P7/02 ,  A61P9/10 ,  A61P9/12 ,  A61P13/12 ,  A61P19/10 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  A61P9/00 ,  A61P11/00 ,  A61P11/06

CPC分类号： C07D209/44

摘要： A 2-iminoimidazole derivative represented by the formula:
{wherein ring C represents a benzene ring, a pyridine ring, etc.; R 1 represents optionally substituted C 1-6 alkyl, etc.; R 201 represents hydrogen, halogen, acyl, etc. ; R 6 represents hydrogen, C 1-6 alkyl, C 1-6 alkyloxycarbonyl, etc.; Y 1 represents a single bond,-CH 2 -, etc.; Y 2 represents a single bond, -CO-, etc.; and Ar represents hydrogen, a group represented by the formula:
[wherein R 10 -R 14 represent hydrogen, C 1-6 alkyl, hydroxyl, C 1-6 alkoxy, etc., and R 11 and R 12 or R 12 and R 13 may bond together to form a 5- to 8-membered heterocycle], etc.} or a salt thereof.

摘要翻译： 由下式表示的2-亚氨基咪唑衍生物：其中环C表示苯环，吡啶环等; R1代表任选取代的C1-6烷基等; R201代表氢，卤素，酰基等; R6代表氢，C1-6烷基，C1-6烷氧基羰基等; Y1表示单键，-CH2-等; Y2表示单键，-CO-等; 并且Ar代表氢，由下式表示的基团：[其中R10-R14表示氢，C1-6烷基，羟基，C1-6烷氧基等，并且R11和R12或R12和R13可以键合在一起形成5 - 至8-元杂环]等等或其盐。

公开(公告)号：EP0719779B1

公开(公告)日：2003-11-19

申请号：EP95921127.7

申请日：1995-06-07

申请人： Eisai Co., Ltd.

发明人： OINUMA, Hitoshi ,  SUDA, Shinji ,  YONEDA, Naoki Tsukubasakuradanchi 906-306 ,  KOTAKE, Makoto ,  MIZUNO, Masanori ,  MATSUSHIMA, Tomohiro ,  FUKUDA, Yoshio ,  SAITO, Mamoru ,  MATSUOKA, Toshiyuki ,  ADACHI, Hideyuki ,  NAMIKI, Masayuki ,  SUDO, Takeshi ,  MIYAKE, Kazutoshi ,  OKITA, Makoto

IPC分类号： C07D513/04 ,  C07D277/06 ,  C07D211/60 ,  A61K31/425

CPC分类号： C07D513/04 ,  A61K38/00 ,  C07K5/06139 ,  Y02P20/55

摘要： A substituted thiazolo[3,2-α]azepine derivative represented by general formula (I) and having the effect of inhibiting an agiotensin I-converting enzyme and an atrial natriuretic peptide hydrolase, wherein R1 represents hydrogen or a thiol-protective group; R2 represents hydrogen, lower alkyl, optionally substituted aryl, optionally substituted heteroaryl, lower alkoxy or lower alkylthio; R?3, R4 and R5¿ represent each independently hydrogen, lower alkyl, lower alkoxy, lower alkylthio, etc., provided the case where all of R?3, R4 and R5¿ are hydrogen atoms at the same time is excepted; R?6 and R7¿ represent each independently hydrogen or lower alkyl; R8 represents hydrogen or a carboxyl-protective group; and m and n represent each independently 0, 1 or 2.

公开(公告)号：EP0671172A1

公开(公告)日：1995-09-13

申请号：EP94917799.2

申请日：1994-06-10

申请人： Eisai Co., Ltd.

发明人： OINUMA, Hitoshi ,  SUDA, Shinji ,  YONEDA, Naoki Tsukubasakuradanchi 906-306 ,  KOTAKE, Makoto ,  HAYASHI, Kenji ,  MIYAKE, Kazutoshi ,  MORI, Nobuyuki ,  SAITO, Mamoru ,  MATSUOKA, Toshiyuki ,  NAMIKI, Masayuki ,  SUDO, Takeshi ,  SOUDA, Shigeru

IPC分类号： A61K31/47 ,  A61K31/55 ,  A61K38/00

CPC分类号： C07D209/48 ,  A61K31/40 ,  A61K31/42 ,  A61K31/44 ,  A61K31/55 ,  C07D223/16 ,  C07D243/12 ,  C07D267/14 ,  C07D281/10 ,  C07D401/06 ,  C07D409/06 ,  C07D471/04 ,  C07D487/04 ,  C07D495/14 ,  C07D513/04 ,  C07K5/06139

摘要： An amino acid derivative having an angiotensin I-converting enzyme inhibitor activity, a vasopressin antagonism and an atrial natriuretic peptide hydrolase inhibitor activity, and represented by general formula (I) wherein R¹ represents hydrogen or acyl; R² represents hydrogen, lower alkyl, cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl; m and n represent each independently an integer of 0.1 or 2; and J represents a cyclic group having an angiotensin I-converting enzyme inhibitor activity.

摘要翻译： 一种具有血管紧张素I转换酶抑制剂活性，加压素拮抗作用和心房钠尿肽水解酶抑制剂活性的氨基酸衍生物，其通式（I）表示，其中R 1代表氢或酰基; R 2代表氢，低级烷基，环烷基，任选取代的芳基，任选取代的杂芳基，任选取代的芳基烷基或任选取代的杂芳基烷基; m和n各自独立地表示0.1或2的整数; J表示具有血管紧张素I转换酶抑制剂活性的环状基团。

公开(公告)号：EP1507773A1

公开(公告)日：2005-02-23

申请号：EP03721353.5

申请日：2003-03-07

申请人： Eisai Co., Ltd

发明人： BOIVIN, Roch ,  CHIBA, Kenichi ,  MURAMOTO, Kenzo ,  SHIROTA, Hiroshi ,  DU, Hong ,  EGUCHI, Yoshihito ,  FUJITA, Masanori ,  GUSOVSKY, Fabian ,  GOTO, Masaki ,  HARMANGE, Jean-Christophe ,  INOUE, Atsushi ,  JIANG, Yimin ,  KAWADA, Megumi ,  KAWAI, Takatoshi ,  KAWAKAMI, Yoshiyuki ,  KIMURA, Akifumi ,  KOTAKE, Makoto ,  KUBOI, Yoshikazu ,  LEMELIN, Charles-André ,  LI, Xiang-Yi ,  MATSUSHIMA, Tomohiro ,  MIZUI, Yoshiharu ,  SAKURAI, Hideki ,  CHOW, Jesse ,  SHEN, Yong-Chun ,  SPYVEE, Mark ,  TANAKA, Isao ,  WANG, John (Yuan) ,  YAMAMOTO, Satoshi ,  YONEDA, Naoki ,  KOBAYASHI, Seiichi

IPC分类号： C07D313/00 ,  A61K31/335 ,  A61P29/00 ,  C07D225/06 ,  C07D407/12 ,  C07D491/04 ,  C07D267/00 ,  C07D493/04 ,  A61K31/36 ,  A61K31/395 ,  A61P11/06 ,  A61P17/06 ,  A61P17/16 ,  A61P19/04 ,  A61P35/00 ,  A61P37/06

CPC分类号： C07D405/12 ,  A61K31/335 ,  A61K31/36 ,  A61K31/395 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D313/00 ,  C07D401/12 ,  C07D491/04 ,  C07D491/044 ,  C07D493/04 ,  Y02A50/411

摘要： The present invention provides compounds having formula (I), and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of various disorders including inflammatory or autoimmune disorders, and disorders involving malignancy or increased angiogenesis, wherein R 1 -R 11 , t, X, Y, Z and n are as defined herein.

公开(公告)号：EP1391451A1

公开(公告)日：2004-02-25

申请号：EP02724628.9

申请日：2002-04-19

申请人： Eisai Co., Ltd.

发明人： SUZUKI, Shuichi ,  KOTAKE, Makoto ,  MIYAMOTO, Mitsuaki ,  KAWAHARA, Tetsuya ,  KAJIWARA, Akiharu ,  HISHINUMA, Ieharu ,  OKANO, Kazuo ,  MIYAZAWA, Syuhei ,  CLARK, Richard ,  OZAKI, Fumihiro ,  SATO, Nobuaki ,  SHINODA, Masanobu ,  KAMADA, Atsushi ,  TSUKADA, Itaru ,  MATSUURA, Fumiyoshi ,  NAOE, Yoshimitsu ,  TERAUCHI, Taro ,  OOHASHI, Yoshiaki ,  ITO, Osamu ,  TANAKA, Hiroshi ,  MUSHA, Takashii ,  KOGUSHI, Motoji ,  KAWADA, Tsutomu ,  MATSUOKA, Toshiuyki ,  KOBAYASHI, Hiroko ,  CHIBA, Keni-ichi ,  KIMURA, Akifumi ,  ONO, Naoto

IPC分类号： C07D209/44

CPC分类号： C07D209/44

摘要： A 2-iminopyrrolidine derivative represented by the formula:
{wherein ring B represents a benzene ring, pyridine ring, etc.; R 101 - R 103 represent hydrogen, halogen, C 1-6 alkyl, etc.; R 5 represents hydrogen, C 1-6 alkyl, C 1-6 alkoxy-C 1-6 alkyl, etc.; R 6 represents hydrogen, C 1-6 alkyl, C 1-6 alkyloxycarbonyl, etc.; Y 1 represents a single bond, -CH 2 -, etc.; Y 2 represents a single bond, -CO-, etc.; and Ar represents hydrogen, a group represented by the formula:
[wherein R 10 -R 14 represent hydrogen, C 1-6 alkyl, hydroxyl, C 1-6 alkoxy, etc.; and R 11 and R 12 or R 12 and R 13 may bond together to form a 5- to 8-membered heterocyclic ring], etc.},
or a salt thereof.

摘要翻译： 由下式表示的2-亚氨基吡咯烷衍生物：环C表示苯环，吡啶环等; R 101 - R 103代表氢，卤素，C 1-6烷基等; R 5表示氢，C 1-6烷基，C 1-6烷氧基-C 1-6烷基等; R 6表示氢，C 1-6烷基，C 1-6烷氧基羰基等; Y 1表示单键，-CH 2 - 等; Y 2表示单键，-CO-等; 和Ar表示氢，由下式表示的基团：其中R 10 -R 14表示氢，C 1-6烷基，羟基，C 1-6烷氧基等; 并且R 11和R 12或R 12和R 13可以键合在一起形成5-至8-元杂环基等，或其盐。

公开(公告)号：EP1391456A1

公开(公告)日：2004-02-25

申请号：EP02718622.0

申请日：2002-04-19

申请人： Eisai Co., Ltd.

发明人： SUZUKI, Shuichi ,  KOTAKE, Makoto ,  MIYAMOTO, Mitsuaki ,  KAWAHARA, Tetsuya ,  KAJIWARA, Akiharu ,  HISHINUMA, Ieharu ,  OKANO, Kazuo ,  MIYAZAWA, Syuhei ,  CLARK, Richard ,  OZAKI, Fumihiro ,  SATO, Nobuaki ,  SHINODA, Masanobu ,  KAMADA, Atsushi ,  TSUKADA, Itaru ,  MATSUURA, Fumiyoshi ,  NAOE, Yoshimitsu ,  TERAUCHI, Taro ,  OOHASHI, Yoshiaki ,  ITO, Osamu ,  TANAKA, Hiroshi ,  MUSYA, Takashi ,  KOGUSHI, Motoji ,  KAWADA, Tsutomu ,  MATSUOKA, Toshiyuki ,  KOBAYASHI, Hiroko ,  CHIBA, Ken-ichi ,  KIMURA, Akifumi ,  ONO, Naoto

IPC分类号： C07D233/88 ,  C07D401/06 ,  A61K31/4168 ,  A61K31/4439 ,  A61K31/4196 ,  A61K31/454

CPC分类号： C07D209/44

摘要： A 2-iminoimidazole derivative represented by the formula:
{wherein R 1 , R 2 and R 3 represent hydrogen, optionally substituted C 1-6 alkyl, etc.; R 6 represents hydrogen, C 1-6 alkyl, C 1-6 alkyloxycarbonyl, etc.; Y 1 represents a single bond, -CH 2 -, etc.; Y 2 represents a single bond, -CO-, etc.; and Ar represents hydrogen, a group represented by the formula:
[wherein R 10 -R 14 represent hydrogen, C 1-6 alkyl, hydroxyl, C 1-6 alkoxy, etc., and R 11 and R 12 or R 12 and R 13 may bond together to form a 5- to 8-membered heterocycle], etc.} or a salt thereof.

摘要翻译： 由下式表示的2-亚氨基咪唑衍生物：其中R1，R2和R3代表氢，任选取代的C1-6烷基等; R6代表氢，C1-6烷基，C1-6烷氧基羰基等; Y1表示单键，-CH2-等; Y2表示单键，-CO-等; 并且Ar代表氢，由下式表示的基团：[其中R10-R14表示氢，C1-6烷基，羟基，C1-6烷氧基等，并且R11和R12或R12和R13可以键合在一起形成5 - 至8-元杂环]等等或其盐。

公开(公告)号：EP1386912A1

公开(公告)日：2004-02-04

申请号：EP02720534.3

申请日：2002-04-19

申请人： Eisai Co., Ltd.

发明人： SUZUKI, Shuichi ,  KOTAKE, Makoto ,  MIYAMOTO, Mitsuaki ,  KAWAHARA, Tetsuya ,  KAJIWARA, Akiharu ,  HISHINUMA, Ieharu ,  OKANO, Kazuo ,  MIYAZAWA, Syuhei ,  CLARK, Richard ,  OZAKI, Fumihiro ,  SATO, Nobuaki ,  SHINODA, Masanobu ,  KAMADA, Atsushi ,  TSUKADA, Itaru ,  MATSUURA, Fumiyoshi ,  NAOE, Yoshimitsu ,  TERAUCHI, Taro ,  OOHASHI, Yoshiaki ,  ITO, Osamu ,  TANAKA, Hiroshi ,  MUSYA, Takashi ,  KOGUSHI, Motoji ,  KAWADA, Tsutomu ,  MATSUOKA, Toshiyuki ,  KOBAYASHI, Hiroko ,  CHIBA, Ken-ichi ,  KIMURA, Akifumi ,  ONO, Naoto

IPC分类号： C07D207/273 ,  A61K31/40 ,  A61K31/4015 ,  A61K31/4025 ,  A61K31/407 ,  A61P7/02 ,  A61P9/10 ,  A61P9/12 ,  A61P13/12 ,  A61P19/10 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  A61P9/00 ,  A61P11/06

CPC分类号： C07D209/44

摘要： A cyclic amidine derivative represented by the formula:
[wherein R 1 , R 2 and R 3 represent hydrogen, C 1-6 alkyl, aryl-C 1-6 alkyl, etc.; R 4 , R 5 and R 7 represent hydrogen, C 1-6 alkyl, etc.; Z represents 0 or 1; R 6 represents hydrogen, C 1-6 alkyl, C 1-6 alkyloxycarbonyl, etc.; n represents 1 or 2; Y 1 represents a single bond, -CH 2 -, etc.; Y 2 represents a single bond, -CO-, etc.; Ar represents hydrogen, a group represented by the formula:
[wherein R 10 -R 14 represent hydrogen, C 1-6 alkyl, hydroxyl, C 1-6 alkoxy, etc., and R 11 and R 12 or R 12 and R 13 may bond together to form a 5- to 8-membered heterocycle], etc.] or a salt thereof.

摘要翻译： 由下式表示的环状脒衍生物：其中R 1，R 2和R 3表示氢，C 1-6烷基，芳基-C 1-6烷基等; R 4，R 5和R 7代表氢，C 1-6烷基等; Z表示0或1; R 6表示氢，C 1-6烷基，C 1-6烷氧基羰基等; n表示1或2; Y 1表示单键，-CH 2 - 等; Y 2表示单键，-CO-等; Ar表示氢，由下式表示的基团：其中R 10 -R 14表示氢，C 1-6烷基，羟基，C 1-6烷氧基等，R 11和R 11， 12>或R 12和R 13可以键合在一起形成5-至8-元杂环或其盐。