Top > Search of International Patents > Bis(arylmethylidene)acetone compound, anti-cancer agent, carcinogenesis-preventive agent, inhibitor of expression of Ki-Ras, ErbB2, c-Myc and Cycline D1, β-catenin-degrading agent, and p53 expression enhancer

Bis(arylmethylidene)acetone compound, anti-cancer agent, carcinogenesis-preventive agent, inhibitor of expression of Ki-Ras, ErbB2, c-Myc and Cycline D1, β-catenin-degrading agent, and p53 expression enhancer

Foreign code F130007253
Posted date Apr 2, 2013
Country United States of America
Application number 99384006
Gazette No. 20100152493
Gazette No. 8178727
Date of filing Jun 27, 2006
Gazette Date Jun 17, 2010
Gazette Date May 15, 2012
International application number JP2006312806
International publication number WO2007000998
Date of international filing Jun 27, 2006
Date of international publication Jan 4, 2007
Priority data
  • P2005-187394 (Jun 27, 2005) JP
  • 2006WO-JP312806 (Jun 27, 2006) WO
Title Bis(arylmethylidene)acetone compound, anti-cancer agent, carcinogenesis-preventive agent, inhibitor of expression of Ki-Ras, ErbB2, c-Myc and Cycline D1, β-catenin-degrading agent, and p53 expression enhancer
Abstract (US8178727)
It has been demanded to improve the poor solubility of curcumin to develop an anti-tumor compound capable of inhibiting the growth of various cancer cells at a low concentration.
Thus, disclosed is a novel synthetic compound, a bis(arylmethylidene)acetone, which has both of an excellent anti-tumor activity and a chemo-preventive activity.
A bis(arylmethylidene)acetone (i.e., a derivative having a curcumin skeleton) which is an anti-tumor compound and has a chemo-preventive activity is synthesized and screened.
A derivative having enhanced anti-tumor activity and chemo-preventive activity can be synthesized.
Scope of claims [claim1]
1. An inhibitor of Ki-Ras, ErbB2, c-Myc, or Cyclin D1 expression; a beta -catenin-degrading agent; a p53 expression enhancer; an anti-cancer agent; or a carcinogenesis chemopreventive agent, which comprises an effective amount of a bis(arylmethylidene)-acetone compound having the Formula:

(wherein R44 is a hydrogen atom or OR34, R33 and R38, which may be identical or different, are independently a member selected from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, an alkoxy group, a hydroxy-alkoxy group, an alkoxyalkoxy group, an alkoxyalkoxyalkoxy group, an alkynyloxy group, and an azido-alkoxy group, or R33 may be taken together with the adjacent substituent OR32 or OR34 to form an alkylene-dioxy bridge, and/or R38 may be taken together with the adjacent substituent OR37 or OR39 to form an alkylene-dioxy bridge, and
R32, R34, R37 or R39, which may be identical or different, are independently a member selected from the group consisting of a hydrogen atom, an alkyl group, an alkynyl group, an alkoxyalkyl group, an alkoxyalkoxyalkyl group and an azido-alkyl group, or may be taken together with the adjacent substituent R33 or R38 to form the aforementioned bridge, provided that
(1) when R44 is a hydrogen atom, R32=R39=an alkyl group, and R33=R38=an hydroxyl atom or an alkoxy group, and
(2) a compound wherein: (a) R44 is OR34, R32=R39=an alkyl group, and R33=R38=a member selected from a hydrogen atom and an alkoxy group, and (b) R44 is OCH3, R32=R37=R39=CH3, and R33=R38.dbd.OH is excluded.
[claim2]
2. The inhibitor according to claim 1, wherein the bis(arylmethylidene)-acetone compound is selected from the group consisting of (1E,4E)-1,5-bis-[3,5-bis(methoxymethoxy)phenyl]penta-1,4-dien-3-one (GO-Y030, BBMMPP),
(1E,4E)-1,5-bis-(3,5-dimethoxy-4-methoxymethoxyphenyl)penta-1,4-dien-3-one (GO-Y031, BDMMMPP),
(1E,4E)-1,5-bis-(3,5-dimethoxy-4-methoxyethoxymethoxy-phenyl)penta-1,4-dien-3-one (GO-Y039),
(1E,4E)-1,5-bis-[4-(2-hydroxyethoxy)-3,5-dimethoxy-phenyl]penta-1,4-dien-3-one (GO-Y044),
(1E,4E)-1-(3,4-dimethoxyphenyl)-5-(3,4,5-trimethoxy-phenyl)penta-1,4-dien-3-one (GO-Y046),
(1E,4E)-1,5-bis-(3,5-dimethoxy-4-prop-2-ynyloxy-phenyl)pentadien-3-one (GO-Y048),
(1E,4E)-1-(3,5-dimethoxy-4-prop-2-ynyloxyphenyl)-5-(3,4,5-trimethoxyphenyl)penta-1,4-dien-3-one (GO-Y060),
(1E,4E)-1-(3,5-bis-methoxymethoxyphenyl)-5-(3,5-dimethoxy-4-prop-2-ynyloxyphenyl)penta-1,4-dien-3-one (GO-Y062),
(1E,4E)-1-(3,5-dimethoxy-4-methoxymethoxyphenyl)-5-(3,5-dimethoxy-4-prop-2-ynyloxyphenyl)penta-1,4-dien-3-one (GO-Y063),
(1E,4E)-1,5-bis-[4-(2-azidoethoxy)-3,5-dimethoxyphenyl]-penta-1,4-dien-3-one (GO-Y065),
or a salt thereof.
[claim3]
3. A bis(arylmethylidene) acetone compound having the Formula:

(wherein R44 is hydrogen or OR34, R33 and R38, which may be identical or different, are independently a member selected from the group consisting of a hydrogen atom, a halogen atom, an hydroxyl group, a nitro group, an alkoxy group, a hydroxy-alkoxy group, an alkoxyalkoxy group, an alkoxyalkoxyalkoxy group, an alkynyloxy group, and an azido-alkoxy group, or R33 may be taken together with the adjacent substituent OR32 or OR34 to form an alkylene-dioxy bridge, and/or R38 may be taken together with the adjacent substituent OR37 or OR39 to form an alkylene-dioxy bridge, and
R32, R34, R37 or R39, which may be identical or different, are independently a member selected from the group consisting of a hydrogen atom, an alkyl group, an alkynyl group, an alkoxyalkyl group, an alkoxyalkoxyalkyl group and an azido-alkyl group, or may be taken together with the adjacent substituent R33 or R38 to form the aforementioned bridge, provided that
(1) when R44 is a hydrogen atom, R32=R39=an alkyl group, and R33=R38=a hydroxyl group or an alkoxy group, and
(2) a compound wherein: (a) R44 is OR34, R32=R39=an alkyl group, and R33=R38=a member selected from a hydrogen group and an alkoxy group, and (b) R44 is OCH3, R32=R37=R39=CH3, and R33=R38 .dbd.OH is excluded.
[claim4]
4. The bis(arylmethylidene)-acetone compound according to claim 3 selected from the group consisting of (1E,4E)-1,5-bis-[3,5-bis(methoxymethoxy)phenyl]penta-1,4-dien-3-one (GO-Y030, BBMMPP),
(1E,4E)-1,5-bis-(3,5-dimethoxy-4-methoxymethoxyphenyl)penta-1,4-dien-3-one (GO-Y031, BDMMMPP),
(1E,4E)-1,5-bis-(3,5-dimethoxy-4-methoxyethoxymethoxy-phenyl)penta-1,4-dien-3-one (GO-Y039),
(1E,4E)-1,5-bis-[4-(2-hydroxyethoxy)-3,5-dimethoxy-phenyl]penta-1,4-dien-3-one (GO-Y044),
(1E,4E)-1-(3,4-dimethoxyphenyl)-5-(3,4,5-trimethoxy-phenyl)penta-1,4-dien-3-one (GO-Y046),
(1E,4E)-1,5-bis-(3,5-dimethoxy-4-prop-2-ynyloxy-phenyl)pentadien-3-one (GO-Y048),
(1E,4E)-1-(3,5-dimethoxy-4-prop-2-ynyloxyphenyl)-5-(3,4,5-trimethoxyphenyl)penta-1,4-dien-3-one (GO-Y060),
(1E,4E)-1-(3,5-bis-methoxymethoxyphenyl)-5-(3,5-dimethoxy-4-prop-2-ynyloxyphenyl)penta-1,4-dien-3-one (GO-Y062),
(1E,4E)-1-(3,5-dimethoxy-4-methoxymethoxyphenyl)-5-(3,5-dimethoxy-4-prop-2-ynyloxyphenyl)penta-1,4-dien-3-one (GO-Y063),
(1E,4E)-1,5-bis-[4-(2-azidoethoxy)-3,5-dimethoxyphenyl]-penta-1,4-dien-3-one (GO-Y065), or a salt thereof.
  • Inventor, and Inventor/Applicant
  • SHIBATA HIROYUKI
  • IWABUCHI YOSHIHARU
  • OHORI HISATSUGU
  • YAMAKOSHI HIROYUKI
  • KAKUDO YUICHI
  • TOHOKU NATIONAL UNIVERSITY
IPC(International Patent Classification)
U.S. Cl./(Sub)
  • C07C049/223
  • C07C049/248
  • C07C049/255
  • C07C205/45
  • C07C247/04
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