Vanadium compounds for treating cancer

Details Vanadium compounds for treating cancer Vanadium compounds for treating cancer

1999-08-20

2002-08-13

Huang, Evelyn Mei (Department: 1625)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

C514S184000, C514S186000, C514S187000, C514S188000, C514S492000, C546S002000, C546S006000, C546S010000, C546S088000, C549S206000, C549S210000, C549S212000

Reexamination Certificate

active

06432941

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to Vanadium (IV) compounds effective for treating tumor cells and particularly effective to induce apoptosis in leukemia cells, breast cancer cells, prostate cancer cells, and brain cancer cells.
BACKGROUND OF THE INVENTION
Cancer is a major disease that continues as one of the leading causes of death at any age. In the United States alone, it is anticipated that more than half a million Americans will die of cancer in 1999. Currently, radiotherapy and chemotherapy are two important methods used in the treatment of cancer.
Considerable efforts are underway to develop new chemotherapeutic agents for more potent and specific anti-cancer therapy, presenting effective and efficient cytotoxicity against tumor cells, with minimal interference with normal cell function. Accordingly, there is an urgent need for the development and analysis of novel, effective anti-cancer agents.
A single vanadocene (IV) compound (e.g., VCp
2
Cl
2
) is reported as having biological activity.
Sakurai, et. al, BBRC, Vol. 206, p. 133 (1995) discloses an oxovanadium compound (e.g., [VO(Phen)(H
2
O)
2
](SO
4
)) that is active against pharyngonasal cancer as determined by a single assay.
Holmes, Ph.D. Thesis, LSU (1961) discloses oxovanadium compounds (e.g., [VO(SO
4
)(Phen)
2
] and [VO(ClO
4
)(Bpy)
2
]) but does not disclose biological data for the compounds.
Selbin, Chem. Rev., Vol. 65, p. 155 (1965) discloses oxovanadium compounds (e.g., [VO(SO
4
)(Phen)
2
] and [VO(ClO
4
)(Bpy)
2
]) but does not disclose biological data for the compounds.
SUMMARY OF THE INVENTION
The invention provides a method for treating cancer in a mammal comprising administering to the mammal in need of such treatment an effective amount of a vanadium (IV) compound; or a pharmaceutically acceptable salt thereof; with the proviso that the vanadium (IV) compound is not VCp
2
Cl
2
or [VO(Phen)(H
2
O)
2
](SO
4
).
The invention also provides a method for treating a mammal inflicted with cancer comprising administering to the mammal in need of such treatment an effective amount of an oxovanadium compound; or a pharmaceutically acceptable salt thereof; with the proviso that the cancer is not pharyngonasal cancer.
The invention also provides a method for treating a mammal inflicted with cancer comprising administering to the mammal in need of such treatment an effective amount of a vanadocene compound; or a pharmaceutically acceptable salt thereof; with the proviso that the vanadocene compound is not VCp
2
Cl
2
.
The invention also provides a compound of formula II:
wherein R and R
1
are each independently H, (C1-C3)alkyl, halogen, (C1-C3)alkoxy, halo(C1-C3)alkyl, cyano, (C
2
-C
6
)alkanoyloxy or nitro; X and X
1
are each independently a monodentate or bidentate ligand, or no ligand is present on X
1
; and Y is a monodentate ligand; or a pharmaceutically acceptable salt thereof; with the proviso that the compound is not [VO(SO
4
)(Bpy)
2
].
The invention also provides a compound of formula III:
wherein R
2
and R
3
are each independently H, (C1-C3)alkyl, halogen, (C1-C3)alkoxy, halo(C1-C3)alkyl, cyano, (C
2
-C
6
)alkanoyloxy or nitro; X
2
and X
3
are each independently a monodentate or bidentate ligand, or no ligand is present on X
3
; and Z is O, CH
2
, CH
2
—CH
2
or CH═CH; or a pharmaceutically acceptable salt thereof; with the proviso that the compound is not [VO(Phen)(H
2
O)
2
](SO
4
) or [VO(SO
4
)(Phen)
2
].
The invention also provides a compound of formula IV:
wherein R
4
, R
5
and R
6
are each independently H, (C1-C3)alkyl, halogen, (C1-C3)alkoxy, halo(C1-C3)alkyl, cyano, (C
2
-C
6
)alkanoyloxy or nitro; X
4
and X
5
are each independently a monodentate or bidentate ligand, or no ligand is present on X
5
; Y is a monodentate ligand, or no ligand is present on X
5
; and Y is a monodentate ligand; or a pharmaceutically acceptable salt thereof; with the proviso that the compound is not [VO(Phen)(H
2
O)
2
](SO
4
) or [VO(SO
4
)(Phen)
2
].
The invention also provides a compound of formula V:
wherein R
7
and R
9
are each independently H, (C1-C3)alkyl, (C1-C3)alkoxy, or halo(C1-C3)alkyl; R
8
is H, (C1-C3)alkyl, halo, (C1-C3)alkoxy, or halo(C1-C3)alkyl; Y and Y
1
are each independently a monodentate or bidentate ligand; and n is 0 or 1; or a pharmaceutically acceptable salt thereof.
The invention also provides a compound of formula VII:
wherein R
1
and R
2
are each independently a cyclopentadienyl ring, wherein any cyclopentadienyl ring may optionally be substituted with one or more (C
1
-C
3
)alkyl; and R
10
-R
13
are each independently H, halo, or (C1-C6)alkyl; or a pharmaceutically acceptable salt thereof.
The invention also provides a pharmaceutical composition comprising a compound of formula II:
wherein R and R
1
are each independently H, (C
1
-C
3
)alkyl, halogen, (C
1
-C
3
)alkoxy, halo(C1-C3)alkyl, cyano, (C
2
-C
6
)alkanoyloxy or nitro; X and are each independently a monodentate or bidentate ligand; or no ligand is present on X
1
; and Y is a monodentate ligand, or no ligand is present on X
1
; and Y is a monodentate ligand or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
The invention also provides a pharmaceutical composition comprising a compound of formula III:
wherein R
2
and R
3
are each independently H, (C1-C3)alkyl, halogen, (C1-C3)alkoxy, halo(C1-C3)alkyl, cyano, (C
2
-C
6
)alkanoyloxy or nitro; X
2
and X
3
are each independently a monodentate or bidentate ligand, or no ligand is present on X
3
; and Z is O, CH
2
, CH
2
—CH
2
or CH═CH; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier; with the proviso that the compound is not [VO(Phen)(H
2
O)
2
](SO
4
).
The invention also provides a pharmaceutical composition comprising a compound of formula IV:
wherein R
4
, R
5
and R
6
are each independently H, (C1-C3)alkyl, halogen, (C1-C3)alkoxy, halo(C1-C3)alkyl, cyano, (C
2
-C
6
)alkanoyloxy or nitro; X
4
and X
5
are each independently a monodentate or bidentate ligand, or no ligand is present on X
5
; Y is a monodentate ligand; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier; with the proviso that the compound is not [VO(Phen)(H
2
O)
2
](SO
4
).


REFERENCES:
patent: 4297341 (1981-10-01), Waller
patent: 4322399 (1982-03-01), Ahmad et al.
patent: 4368186 (1983-01-01), Vickery et al.
patent: 4432967 (1984-02-01), Szymanski
patent: 4559157 (1985-12-01), Smith et al.
patent: 4588581 (1986-05-01), Schmolka
patent: 4608387 (1986-08-01), Kopf et al.
patent: 4608392 (1986-08-01), Jacquet et al.
patent: 4613497 (1986-09-01), Chavkin
patent: 4707362 (1987-11-01), Nuwayser
patent: 4795425 (1989-01-01), Pugh
patent: 4820508 (1989-04-01), Wortzman
patent: 4917901 (1990-04-01), Bourbon et al.
patent: 4938949 (1990-07-01), Borch et al.
patent: 4992478 (1991-02-01), Geria
patent: 4999342 (1991-03-01), Ahmad et al.
patent: 5013544 (1991-05-01), Chantler et al.
patent: 5021595 (1991-06-01), Datta
patent: 5069906 (1991-12-01), Cohen et al.
patent: 5300496 (1994-04-01), McNeill et al.
patent: 5387611 (1995-02-01), Rubinstein
patent: 5407919 (1995-04-01), Brode et al.
patent: 5512289 (1996-04-01), Tseng et al.
patent: 5595980 (1997-01-01), Brode et al.
patent: 5877210 (1999-03-01), Schieven
patent: 293 495 (1991-09-01), None
patent: 0 407 804 (1990-06-01), None
patent: WO 97/47296 (1997-12-01), None
Sof'ina et al. Nationa Cancer Institute Monograph 55. NIH Publication No. 80-1933. Experimental Evalutation of Antitumor Drugs in the USA and USSR and Clinical Correlations. Dec., 1980.*
Islam M et al. J. Bangladesh Chem. soc. (1992), 5(2), 121-6.*
Demsar A et al. J. Fluorine Chem. (1984), 24(3), 369-75.*
Filgueiras C et al. Transition Met. Chem. 9Weinheim, Ger.) (1981), 6(5), 258-60.*
Aistars, A. et al., 1997,Organometallics, vol. 16, pp. 1994-1996 “Convenient Synthesis of Dichloro(oxo)(pentamethylcyclopen

Affiliated with

Also associated with

Rating

Vanadium compounds for treating cancer does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Vanadium compounds for treating cancer, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Vanadium compounds for treating cancer will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2880383