Title:
【発明の名称】プロテアソーム・インヒビターとしての2,4-ジアミノ-3-ヒドロキシカルボン酸誘導体の使用
Document Type and Number:
Japanese Patent JP2002543058
Kind Code:
A
Abstract:
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.
Inventors:
Denise France
Peter Furst
Johann Zimmermann
Carlos Garcia-Echeveria
Dieter Scholz
Pascal Fure
Patrizia Imbach
Peter Furst
Johann Zimmermann
Carlos Garcia-Echeveria
Dieter Scholz
Pascal Fure
Patrizia Imbach
Application Number:
JP2000613816A
Publication Date:
December 17, 2002
Filing Date:
April 25, 2000
Export Citation:
Assignee:
Novartis Actien Gezel Shaft
International Classes:
A61P17/06; A61P35/00; A61P43/00; C07C237/12; C07C271/22; C07K5/00; A61K38/00; (IPC1-7): A61K38/00; A61P17/06; A61P35/00; C07C237/12; C07C271/22; C07K5/00
Domestic Patent References:
| JPH0789919A | 1995-04-04 | |||
| JPH07501786A | 1995-02-23 | |||
| JPS5344634A | 1978-04-21 |
Other References:
JPN6010053994, ＡＩＤＳ, 1998, Ｖｏｌ．１２ Ｎｏ．７, ｐｐ．Ｆ４５−Ｆ４９
JPN6010053995, Ｊ． Ｍｅｄ． Ｃｈｅｍ．, 1975, Ｖｏｌ．１８ Ｎｏ．４, ｐｐ．３５４−３５８
JPN6010053996, Ｂｉｏｃｈｅｍ． Ｐｈａｒｍａｃｏｌ．, 1977, Ｖｏｌ．２６ Ｎｏ．１５, ｐｐ．１４０５−１４１０
JPN6010053995, Ｊ． Ｍｅｄ． Ｃｈｅｍ．, 1975, Ｖｏｌ．１８ Ｎｏ．４, ｐｐ．３５４−３５８
JPN6010053996, Ｂｉｏｃｈｅｍ． Ｐｈａｒｍａｃｏｌ．, 1977, Ｖｏｌ．２６ Ｎｏ．１５, ｐｐ．１４０５−１４１０
Attorney, Agent or Firm:
Aoyama Ryo (2 outside people)