公开(公告)号：EP1445249B1

公开(公告)日：2012-11-07

申请号：EP02781763.4

申请日：2002-11-13

Applicant: TOYAMA CHEMICAL CO., LTD.

Inventor： CHAKI, Hisaaki ,  KOTSUBO, Hironori ,  TANAKA, Tadashi ,  AIKAWA, Yukihiko ,  HIRONO, Shuichi ,  SHIOZAWA, Shunichi

IPC: C07C59/90 ,  C07C69/734 ,  C07C69/76 ,  C07C205/34 ,  C07C219/32 ,  C07C255/54 ,  C07C255/37 ,  C07C271/64 ,  C07C235/42 ,  C07C311/29 ,  C07C311/51 ,  C07D333/56 ,  C07D333/38 ,  C07D409/12 ,  C07D239/96 ,  C07D261/20 ,  A61K31/192 ,  A61P29/00

CPC classification number: C07C235/42 ,  A61K31/192 ,  C07C59/90 ,  C07C65/34 ,  C07C65/40 ,  C07C69/738 ,  C07C69/76 ,  C07C69/88 ,  C07C69/94 ,  C07C205/34 ,  C07C217/76 ,  C07C255/54 ,  C07C259/10 ,  C07C271/64 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/10 ,  C07C2601/14 ,  C07C2601/18

公开(公告)号：EP1076056A1

公开(公告)日：2001-02-14

申请号：EP99918266.0

申请日：1999-04-28

Applicant: TOYAMA CHEMICAL CO., LTD.

Inventor： CHAKI, Hisaaki ,  AIKAWA, Yukihiko ,  MIYAJIMA, Mikako ,  TAKAKURA, Tadakazu ,  NISHIO, Morihiro ,  KURODA, Hiroshi ,  TANAKA, Keiichi ,  KAJITA, Tetsuya ,  HIRONO, Shuichi ,  SHIOZAWA, Shunichi

IPC: C07D277/60 ,  C07D417/04 ,  C07D417/06 ,  C07D513/10 ,  C07K5/04 ,  A61K31/425 ,  A61K31/44 ,  A61K31/445 ,  A61K38/04

CPC classification number: C07D277/60 ,  A61K38/00 ,  C07D417/04 ,  C07D417/06 ,  C07D417/08 ,  C07D417/12 ,  C07D513/10 ,  C07K5/06139

Abstract: The spiro compounds of the present invention represented by the following general formula:
wherein A, R 2 , R 3 , R 4 , R 5 , R 6 and n are as defined in the specification, exhibit an AP-1 activity inhibitory action and, based on the AP-1 inhibitory action, suppresses the expression of a wide variety of genes and are useful as an agent for treating and preventing autoimmune diseases with lessened side reactions.

Abstract translation: 如在定义 worin A，R <2> [R <3>，R <4> - [R <5> - [R <6>和n：由下述通式表示的本发明的螺环化合物 AP-1活性抑制作用的说明书中，表现出和，基于AP-1抑制作用，抑制了各种基因的表达，并且作为用于治疗和减轻与副反应预防自身免疫性疾病的药剂是有用的。

公开(公告)号：EP1445249A1

公开(公告)日：2004-08-11

申请号：EP02781763.4

申请日：2002-11-13

Applicant: TOYAMA CHEMICAL CO., LTD. ,  Hirono, Shuichi ,  Shiozawa, Shunichi

Inventor： CHAKI, Hisaaki ,  KOTSUBO, Hironori ,  TANAKA, Tadashi ,  AIKAWA, Yukihiko ,  HIRONO, Shuichi ,  SHIOZAWA, Shunichi

IPC: C07C59/90 ,  C07C69/734 ,  C07C69/76 ,  C07C205/34 ,  C07C219/32 ,  C07C255/54 ,  C07C255/37 ,  C07C271/64 ,  C07C235/42 ,  C07C311/29 ,  C07C311/51 ,  C07C311/53 ,  C07C317/22 ,  C07C323/19 ,  A61K31/192

CPC classification number: C07C235/42 ,  A61K31/192 ,  C07C59/90 ,  C07C65/34 ,  C07C65/40 ,  C07C69/738 ,  C07C69/76 ,  C07C69/88 ,  C07C69/94 ,  C07C205/34 ,  C07C217/76 ,  C07C255/54 ,  C07C259/10 ,  C07C271/64 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/10 ,  C07C2601/14 ,  C07C2601/18

Abstract: A benzophenone derivative represented by the following formula:
wherein

R 1 represents, for example, an optionally substituted heterocyclic group, or a substituted phenyl group; Z represents, for example, an alkylene group; R 2 represents, for example, a carboxyl group optionally protected with alkyl;
R 3 represents, for example, an optionally protected hydroxyl group; R 4 represents, for example, an optionally substituted cycloalkyloxy group; and R 5 represents, for example, a hydrogen atom,
   or a salt thereof has anti-arthritic activity, inhibits bone destruction caused by arthritis, and provides high safety and excellent pharmacokinetics and thus is useful as therapeutic agent for arthritis. These compounds have inhibitory effect on AP-1 activity and are useful as preventive or therapeutic agent for diseases in which excessive expression of AP-1 is involved.

公开(公告)号：EP1127869A1

公开(公告)日：2001-08-29

申请号：EP99954398.6

申请日：1999-11-05

Applicant: TOYAMA CHEMICAL CO., LTD.

Inventor： CHAKI, Hisaaki ,  TAKAKURA, Tadakazu ,  TSUCHIDA, Keiichi ,  YOKOTANI, Junichi ,  KOTSUBO, Hironori ,  AIKAWA, Yukihiko ,  HIRONO, Shuichi ,  SHIOZAWA, Shunichi

IPC: C07C69/73 ,  C07C69/767 ,  C07C205/49

CPC classification number: C07D207/333 ,  A61K38/00 ,  C07C59/64 ,  C07C59/84 ,  C07C65/24 ,  C07C65/34 ,  C07C65/36 ,  C07C65/38 ,  C07C65/40 ,  C07C69/738 ,  C07C69/94 ,  C07C229/34 ,  C07C233/01 ,  C07C233/47 ,  C07C235/20 ,  C07C235/84 ,  C07C251/32 ,  C07C251/48 ,  C07C251/60 ,  C07C255/49 ,  C07C275/24 ,  C07C311/06 ,  C07C311/51 ,  C07D207/08 ,  C07D209/42 ,  C07D235/26 ,  C07D277/60 ,  C07K7/06 ,  C07K7/64 ,  Y02P20/55

Abstract: A compound comprising the atom corresponding to N 3 and the two or more atoms selected from N 1 , N 2 , N 4 and N 5 , said atoms constitute the pharmacophore represented by the following formula:
wherein N 1 represents an atom to which a donative hydrogen atom in a hydrogen-bond donating group is bonded or a hydrogen-bond accepting atom in a hydrogen-bond accepting group; N 3 represents a hydrogen-bond accepting atom in a hydrogen-bond accepting group; and N 2 , N 4 and N 5 independently represents an arbitrary carbon atom constituting a hydrophobic group and defined by the interatomic distances between N 1 , N 2 , N 3 , N 4 and N 5 ; and, in the optimized three-dimensional structure thereof, the distances between the atom corresponding to N 3 and the two or more atoms selected from N 1 , N 2 , N 4 and N 5 , in the optimized steric structure thereof, are the interatomic distances in a pharmacophore; or a salt thereof;
   inhibits the activity of transcription factor AP-1 and is useful as an agent for preventing and treating the diseases into which overexpression of AP-1 participates and as an AP-1 inhibitor.

Abstract translation: 包含对应于N 3的原子和选自N1，N2，N4和N5的两个或更多个原子的化合物，所述原子构成由下式表示的药效团：其中N1表示与 在氢键接受基团中键合氢键供体基团或氢键接受原子; N3表示氢键接受基团中的氢键接受原子; N2，N4和N5独立地表示构成疏水基团的任意碳原子，由N1，N2，N3，N4和N5之间的原子间距离定义; 并且在其优化的三维结构中，在其优化的立体结构中，对应于N 3的原子与选自N1，N2，N4和N5的两个或更多个原子之间的距离是药效团中的原子间距离; 或其盐; 抑制转录因子AP-1的活性，可用作预防和治疗AP-1过表达的疾病和作为AP-1抑制剂的药物。