Title:
METAL COMPLEXES HAVING DUAL HISTONE DEACETYLASE INHIBITORY AND DNA-BINDING ACTIVITY
Document Type and Number:
WIPO Patent Application WO/2011/006908
Kind Code:
A3
Abstract:
Compounds comprising a metal complex having the structure [X-Y-Z-Mn+]p+. B are disclosed in which X is a histone deacetylase inhibitor, Mn+ is a DNA -binding heavy metal ion, Y is an aliphatic or aromatic spacer or is absent, and Z is a mono- or bi-dentate or chelating donor linker, or a bridging linker, P+ designates the charge on the complex ion, which may be positive, negative or absent and B is a counterion or is absent. The linker Z is labile and its metal complex X-Y-Z-Mn+ is capable of being hydrolysed in-vivo. The compounds find application in the treatment of cancer.
Inventors:
MARMION CELINE JOSEPHINE (IE)
GRIFFITH DARREN (IE)
GRIFFITH DARREN (IE)
Application Number:
PCT/EP2010/060089
Publication Date:
March 03, 2011
Filing Date:
July 13, 2010
Export Citation:
Assignee:
ROYAL COLLEGE SURGEONS IRELAND (IE)
MARMION CELINE JOSEPHINE (IE)
GRIFFITH DARREN (IE)
MARMION CELINE JOSEPHINE (IE)
GRIFFITH DARREN (IE)
International Classes:
C07F15/00; A61K31/28; C07C259/06; C07C311/21; C07F19/00
Domestic Patent References:
| WO2007056243A2 | 2007-05-18 | |||
| WO2000074681A1 | 2000-12-14 |
Foreign References:
| US20050119305A1 | 2005-06-02 |
Other References:
STOERMER, D. ET AL.: "Symthesis and biological evaluation of hydroxamate-based inhibito of glutamate carboxypeptidase II", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, pages 2097 - 2100, XP002612571
UTTAMCHANDANI, M. ET AL: "Inhibitor fingerprinting of matrix metalloproteases using a combinatorial peptide hydroxamate library", THE JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, pages 7848 - 7858, XP002612572
SALMI-SMAIL, C. ET AL.: "Modified cap group suberoylanilide hydroxamic acid histone deacetylase inhibitor derivatives reveal improved selective antileukemic activity", JOURNAL OF MEDICINAL CHEMISTRY, 10 March 2010 (2010-03-10), pages 3038 - 3047, XP002612573
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 1989, XIE, J. ET AL.: "Inhibitors of the enkephalin degrading enzymes. Modulation of activity of hydroxamate containing compounds by modifications of the C-terminal residue", XP002612574, retrieved from STN Database accession no. 112:154184
GRIFFITH, D. ET AL.: "A novel anti-cancer bifunctional platinum drug candidate with dual DNA binding and histone deacetylase inhibitory activity", CHEMICAL COMMUNICATIONS, 12 October 2010 (2010-10-12), pages 6735 - 6737, XP002612575
UTTAMCHANDANI, M. ET AL: "Inhibitor fingerprinting of matrix metalloproteases using a combinatorial peptide hydroxamate library", THE JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, pages 7848 - 7858, XP002612572
SALMI-SMAIL, C. ET AL.: "Modified cap group suberoylanilide hydroxamic acid histone deacetylase inhibitor derivatives reveal improved selective antileukemic activity", JOURNAL OF MEDICINAL CHEMISTRY, 10 March 2010 (2010-03-10), pages 3038 - 3047, XP002612573
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 1989, XIE, J. ET AL.: "Inhibitors of the enkephalin degrading enzymes. Modulation of activity of hydroxamate containing compounds by modifications of the C-terminal residue", XP002612574, retrieved from STN Database accession no. 112:154184
GRIFFITH, D. ET AL.: "A novel anti-cancer bifunctional platinum drug candidate with dual DNA binding and histone deacetylase inhibitory activity", CHEMICAL COMMUNICATIONS, 12 October 2010 (2010-10-12), pages 6735 - 6737, XP002612575
Attorney, Agent or Firm:
PURDY, Hugh Barry (138-139 The Capel BuildingMary's Abbey, Dublin D7, IE)
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