公开(公告)号：EP0603399A1

公开(公告)日：1994-06-29

申请号：EP93900411.5

申请日：1992-12-28

申请人： KYOWA HAKKO KOGYO KABUSHIKI KAISHA

发明人： TANAKA, Takeo ,  MORISHITA, Yoshikazu ,  NOZAWA, Mika ,  CHIBA, Shigeru ,  KAWAMOTO, Isao ,  TSUKUDA, Eiji ,  YOSHIDA, Mayumi ,  SHIMAZAKI, Chieko ,  YAMAGUCHI, Kazuo ,  MATSUDA, Yuzuru ,  KITAMURA, Shigeto ,  IKEMURA, Toshihide ,  OGAWA, Tatsuhiro ,  YANO, Keiichi ,  SUZAWA, Toshiyuki ,  SHIBATA, Kenji ,  YAMASAKI, Motoo

IPC分类号： C12P21/00

CPC分类号： C07K7/06 ,  A61K38/00 ,  C07K5/1021 ,  C07K5/1024 ,  C07K7/08 ,  C07K14/36 ,  C07K14/57536

摘要： A novel peptide represented by the following general formula and a process for producing the same: X-A-Trp-B-Gly-Thr-E-G-Y wherein, A represents Asn or Asp; B represents His or Lys; E represents Ala or Ser; G represents Ala or Pro; X represents X¹-Gly or X³-Cys-X²; and Y represents hydroxy, lower alkoxy, amino, Y¹-Asp-Z or Y²-Cys-Z. The peptide is isolated from the product of culture of a streptomyces and has an endothelin antagonism and an activity of suppressing the rise of an intracellular calcium or cyclic guanosine-3,5-phosphate concentration caused by endothelin.

摘要翻译： 由以下通式表示的新肽及其制备方法：X-A-Trp-B-Gly-Thr-E-G-Y其中A表示Asn或Asp; B代表His或Lys; E表示Ala或Ser; G代表Ala或Pro; X表示X 1 -Gly或X 3 -Cys-X 2; Y表示羟基，低级烷氧基，氨基，Y 1 -Asp-Z或Y 2 -Cys-Z。 该肽从链霉菌培养物的产物中分离，具有内皮素拮抗作用和抑制由内皮素引起的细胞内钙或环鸟苷-3磷酸盐浓度升高的活性。

公开(公告)号：EP0603399B1

公开(公告)日：2002-09-11

申请号：EP93900411.5

申请日：1992-12-28

申请人： KYOWA HAKKO KOGYO KABUSHIKI KAISHA

发明人： TANAKA, Takeo ,  MORISHITA, Yoshikazu ,  NOZAWA, Mika ,  CHIBA, Shigeru ,  KAWAMOTO, Isao ,  TSUKUDA, Eiji ,  YOSHIDA, Mayumi ,  SHIMAZAKI, Chieko ,  YAMAGUCHI, Kazuo ,  MATSUDA, Yuzuru ,  KITAMURA, Shigeto ,  IKEMURA, Toshihide ,  OGAWA, Tatsuhiro ,  YANO, Keiichi ,  SUZAWA, Toshiyuki ,  SHIBATA, Kenji ,  YAMASAKI, Motoo

IPC分类号： C12P21/00 ,  C07K7/00

CPC分类号： C07K7/06 ,  A61K38/00 ,  C07K5/1021 ,  C07K5/1024 ,  C07K7/08 ,  C07K14/36 ,  C07K14/57536

公开(公告)号：EP0882717A1

公开(公告)日：1998-12-09

申请号：EP97943133.5

申请日：1997-10-01

申请人： KYOWA HAKKO KOGYO KABUSHIKI KAISHA

发明人： MATSUNO, Kenji ,  ICHIMURA, Michio ,  NOMOTO, Yuji ,  FUJIWARA, Shigeki ,  IDE, Shinichi ,  TSUKUDA, Eiji ,  IRIE, Junko ,  ODA, Shoji

IPC分类号： C07D215/46 ,  C07D217/22 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D487/04 ,  A61K31/495 ,  A61K31/50 ,  A61K31/535

CPC分类号： C07D401/12 ,  A61K31/496 ,  A61K31/502 ,  A61K31/517 ,  C07D215/46 ,  C07D217/22 ,  C07D237/34 ,  C07D239/94 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D487/04

摘要： The present invention provides nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salts thereof which inhibit phosphorylation of PDGF receptor to hinder abnormal cell growth and cell wandering and thus are useful for the prevention or treatment of cell-proliferative diseases such as arteriosclerosis, vascular reobstruction, cancer and glomerulosclerosis. The compounds are represented by general formula (I):


wherein V represents an oxygen atom or a sulfur atom;
W represents 1,4-piperazinediyl or 1,4-homopiperazinediyl in which carbons on the ring may be substituted by unsubstituted alkyl groups;
X represents a nitrogen atom or C-R 9 ;
Y represents a nitrogen atom or C-R 8 ;
Z represents a nitrogen atom or C-R 7 (provided that at least one of X, Y and Z represents a nitrogen atom);
R 1 represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, etc.;
R 2 represents a substituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, etc.;
R 3 , R 4 , R 5 and R 6 , which may be the same or different, each represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a nitro group, a cyano group, - OR 12 , -NR 15 R 16 , etc.;
R 7 represents a halogen atom, etc.;
R 8 has the same significance as R 7 , and
R 9 represents a hydrogen atom or -COR 41 .

摘要翻译： 本发明提供了抑制PDGF受体磷酸化的含氮杂环化合物及其药学上可接受的盐，以阻止异常的细胞生长和细胞游动，因此可用于预防或治疗细胞增殖性疾病如动脉硬化，血管重构，癌症 和肾小球硬化症。 化合物由通式（I）表示：其中V表示氧原子或硫原子; W代表1,4-哌嗪二基或1,4-高哌嗪二基，其中环上的碳可以被未取代的烷基取代; X表示氮原子或C-R 9; Y表示氮原子或C-R 8; Z表示氮原子或C-R 7（条件是X，Y和Z中的至少一个表示氮原子）; R 1表示氢原子，取代或未取代的烷基，取代或未取代的脂环族烷基等; R 2表示取代的烷基，取代或未取代的脂环族烷基等; R 3，R 4，R 5和R 6可以相同或不同，分别表示氢原子，卤素原子，取代或未取代的烷基，硝基， 氰基，-OR 12，-NR 15 R 16等; R 7表示卤素原子等; R 8与R 7具有相同的含义，R 9表示氢原子或-COR 41。