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Title:
医薬活性なオルニチン誘導体、それのアンモニウム塩およびそれの製造方法
Document Type and Number:
Japanese Patent JP2006523689
Kind Code:
A
Abstract:
In one embodiment, the present invention relates to a new class of ammonium salts of Ndelta-acyl derivatives of Nalpha-(4-amino-4-deoxypteroyl)-L-ornithine compounds having a structure according to formula II-IV. Formula II has the structure of: wherein: R2 represents up to four groups independently selected at each occurrence of R2 from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C1-6 alkoxy, chloro, fluoro, hydroxy, and -COOH; R3, R4, and R5 are each independently selected from hydrogen and C1-6 alkyl; or NR3R4 taken combination can form a 5 to 7 member heterocycle having at least one nitrogen ring atom; and x is a real number greater than 0 and less than about 4. The ammonium salts provided by the invention exhibit high inhibitory activity against the growth o methotrexate-resistant cells, and also exhibit superior chemical stability than corresponding acidic Ndelta-acyl derivatives of Ndelta-acyl derivatives of Nalpha(4-amino-4-deoxypteroyl)-L-ornithine compounds.

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Inventors:
Rossousky, Andre
Henry Badder
Bloombergs, Peter
Lynn, Min-Ta
Application Number:
JP2006508804A
Publication Date:
October 19, 2006
Filing Date:
February 23, 2004
Export Citation:
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Assignee:
Dana Faber Cancer Institute
Ash Stevens, Incorporated
International Classes:
C07D475/08; A61K31/519; A61P35/00; A61P43/00; C07D471/04
Domestic Patent References:
JPH02502095A1990-07-12
JPH0725876A1995-01-27
JPH10310526A1998-11-24
JP2002212183A2002-07-31
Other References:
JPN5006005758, ＡＮＤＲＥ　ＲＯＳＯＷＳＫＹ, ＰＨＡＲＭＡＣＯＬＯＧＹ　ＡＮＤ　ＴＨＥＲＡＰＥＵＴＩＣＳ, 2000, Ｖ８５, Ｐ１９１−２０５, GB, ＥＬＳＥＶＩＥＲ
JPN6010027450, Ｒｏｓｏｗｓｋｙ，Ａ．，ｅｔ　ａｌ, Ｊｏｕｒｎａｌ　ｏｆ　Ｍｅｄｉｃｉｎａｌ　Ｃｈｅｍｉｓｔｒｙ, 1997, Ｖｏｌ．４０, ｐｐ　２８６−２９９
JPN6009014198, Ｊｏｕｒｎａｌ　ｏｆ　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｓｃｉｅｎｃｅｓ, 1977, Ｖｏｌ．６６，　Ｎｏ．１, ｐａｇｅｓ　１−１９
Attorney, Agent or Firm:
Yusuke Hiraki
Ishii Teiji
Satoshi Fujita



 
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