发明公开
EP1173413A1 USE OF 2,4-DIAMINO-3-HYDROXYCARBOXYLIC ACID DERIVATIVES AS PROTEASOME INHIBITORS
有权
2,4-二氨基-3-HYDROXYCARBOXYLSÄUREDERIVATEALS蛋白酶体抑制剂
- 专利标题: USE OF 2,4-DIAMINO-3-HYDROXYCARBOXYLIC ACID DERIVATIVES AS PROTEASOME INHIBITORS
- 专利标题(中): 2,4-二氨基-3-HYDROXYCARBOXYLSÄUREDERIVATEALS蛋白酶体抑制剂
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申请号: EP00927038.0申请日: 2000-04-25
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公开(公告)号: EP1173413A1公开(公告)日: 2002-01-23
- 发明人: FRANCE, Dennis , FÜRST, Peter , ZIMMERMANN, Johann , GARCIA-ECHEVERRIA, Carlos , SCHOLZ, Dieter , FURET, Pascal , IMBACH, Patricia
- 申请人: Novartis AG , Novartis-Erfindungen Verwaltungsgesellschaft m.b.H.
- 申请人地址: Lichtstrasse 35 4056 Basel CH
- 专利权人: Novartis AG,Novartis-Erfindungen Verwaltungsgesellschaft m.b.H.
- 当前专利权人: Novartis AG,Novartis-Erfindungen Verwaltungsgesellschaft m.b.H.
- 当前专利权人地址: Lichtstrasse 35 4056 Basel CH
- 代理机构: Becker, Konrad
- 优先权: US300779 19990427; US388700 19990902
- 国际公布: WO0064863 20001102
- 主分类号: C07C271/22
- IPC分类号: C07C271/22 ; A61P43/00 ; A61K31/325
摘要:
The present invention relates to the new use of 2,4-diamino-3-hydroxycarboxylic acids of formula (I), in which A and B independently represent a bond or an unsubstituted or substituted amino acyl moiety; R1 represents hydrogen; an amino protecting group; or a group of formula R5Y- wherein R5 represents hydrogen or an unsubstituted or substituted alkyl, alkenyl, alkinyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl group; and Y represents -CO-; -NH-CO-; -NH-CS-; -SO2-; -O-CO-; or -O-CS-; R2 represents the side chain of a natural amino acid; an alkyl, arylalkyl, heteroarylalkyl or cycloalkylalkyl group; or trimethylsilylmethyl, 2-thienylmethyl or styrylmethyl; R3 represents halogen, alkyl, alkoxy or hydroxyalkoxy; and R4 represents 2(R)-hydroxyindan-1(S)-yl; (S)-2-hydroxy-1-phenylethyl; or 2-hydroxy-benzyl unsubstituted or substituted in 4-position by methoxy; in the manufacture of a pharmaceutical composition for the treatment of a proliferative disease, e.g. of a solid tumor; to a method of treatment of warm-blooded animals; and to 2,4-diamino-3-hydroxycarboxylic acids of formula (I*), wherein A and B independently represent an unsubstituted or substituted amino acyl moiety; R2 represents arylalkyl; R3 represents halogen, alkyl, alkoxy or hydroxyalkoxy; R4 represents 2-hydroxy-benzyl unsubstituted or substituted in 4 position by methoxy; and R5 represents arylalkyl and Y represents -CO-; or R5 represents alkyl substituted by cycloalkyl, naphthyl, pyridyl or phenyl in which phenyl is substituted by alkyl or amino; and Y represents -O-CO; pharmaceutically acceptable salts thereof; and the use of such compounds of formula (I*) for the therapeutic treatment of the human or animal body, especially the treatment of proliferative diseases.
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