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  Vanadium compounds for treating cancerUSPTO Application #: 20060106006Title: Vanadium compounds for treating cancer Abstract: The invention provides methods for treating cancer and compounds that are useful for the treatment of tumors, as well as pharmaceutical compositions comprising the compounds, and synthetic methods and intermediates useful for preparing the compounds. (end of abstract)
Agent: Attention Of John L. Haack, Ph.d. Merchant & Gould P.C. - Minneapolis, MN, US Inventors: Fatih M. Uckun, Yanhong Dong, Phalguni Gosh USPTO Applicaton #: 20060106006 - Class: 514184000 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Heavy Metal Containing (including Salts) The Patent Description & Claims data below is from USPTO Patent Application 20060106006. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a divisional of application Ser. No. 10/857,440, filed May 28, 2004, which is a divisional of application Ser. No. 10/142,305, filed May 8, 2002, now U.S. Pat. No. 6,743,786, which is a divisional of application Ser. No. 09/378,531, filed Aug. 20, 1999, now U.S. Pat. No. 6,432,941, which claim priority to provisional application Ser. No. 60/097,377, filed Aug. 21, 1998 and is a continuation-in-part of application Ser. No. 09/187,115, filed Nov. 5, 1998, now U.S. Pat. No. 6,245,808 and a continuation-in-part of application Ser. No. 09/008,898, filed Jan. 20, 1998, now U.S. Pat. No. 6,051,603, which applications are incorporated herein by reference. FIELD OF THE INVENTION [0002] 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 [0003] 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. [0004] 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. [0005] A single vanadocene (IV) compound (e.g., VCp.sub.2Cl.sub.2) is reported as having biological activity. [0006] Sakurai, et. al, BBRC, Vol. 206, p. 133 (1995) discloses an oxovanadium compound (e.g., [VO(Phen)(H.sub.2O.sub.2](SO.sub.4)) that is active against pharyngonasal cancer as determined by a single assay. [0007] Holmes, Ph.D. Thesis, LSU (1961) discloses oxovanadium compounds (e.g., [VO(SO.sub.4)(Phen).sub.2] and [VO(ClO.sub.4)(Bpy).sub.2]) but does not disclose biological data for the compounds. [0008] Selbin, Chem. Rev., Vol. 65, p. 155 (1965) discloses oxovanadium compounds (e.g., [VO(SO.sub.4)(Phen).sub.2] and [VO(ClO.sub.4)(Bpy).sub.2]) but does not disclose biological data for the compounds. SUMMARY OF THE INVENTION [0009] 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 parmaceutically acceptable salt thereof; with the proviso that the vanadium (IV) compound is not VCp.sub.2Cl.sub.2 or [VO(Phen)(H.sub.2O).sub.2](SO.sub.4). [0010] 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. [0011] 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 pharmaeutically acceptable salt thereof; with the proviso that the vanadocene compound is not VCp.sub.2Cl.sub.2. [0012] The invention also provides a compound of formula II: wherein R and R.sup.1 are each independently H, (C1-C3)alkyl, halogen, (C1-C3)alkoxy, halo(C1-C3)alkyl, cyano, (C.sub.2-C.sub.6)alkanoyloxy or nitro; X and X.sup.1 are each independently a monodentate or bidentate ligand, or no ligand is present on X.sub.1; and Y is a monodentate ligand; or a pharmaceutically acceptable salt thereof; with the proviso that the compound is not [VO(SO.sub.4)(Bpy).sub.2]. [0013] The invention also provides a compound of formula III: wherein R.sup.2and R.sup.3 are each independently H, (C1-C3)alkyl, halogen, (C1-C3)alkoxy, halo(C1-C3)alkyl, cyano, (C.sub.2-C.sub.6)alkanoyloxy or nitro; X.sup.2 and X.sup.3 are each independently a monodentate or bidentate ligand, or no ligand is present on X.sup.3; and Z is O, CH.sub.2, CH.sub.2--CH.sub.2 or CH.dbd.CH; or a pharmaceutically acceptable salt thereof; with the proviso that the compound is not [VO(Phen)(H.sub.2O).sub.2](SO.sub.4) or [VO(SO.sub.4)(Phen).sub.2]. [0014] The invention also provides a compound of formula IV: wherein R.sup.4, R.sup.5 and R.sup.6 are each independently H, (C1-C3)alkyl, halogen, (C1-C3)alkoxy, halo(C1-C3)alkyl, cyano, (C.sub.2-C.sub.6)alkanoyloxy or nitro; X.sup.4 and X.sup.5 are each independently a monodentate or bidentate ligand, or no ligand is present on X.sup.5; Y is a monodentate ligand, or no ligand is present on X.sup.5; and Y is a monodentate ligand; or a pharmaceutically acceptable salt thereof; with the proviso that the compound is not [VO(Phen)(H.sub.2O).sub.2](SO.sub.4) or [VO(SO.sub.4)(Phen).sub.2]. [0015] The invention also provides a compound of formula V: wherein R.sup.7 and R.sup.9 are each independently H, (C1-C3)alkyl, (C1-C3)alkoxy, or halo(C1-C3)alkyl; R.sup.8 is H, (C1-C3)alkyl, halo, (C1-C3)alkoxy, or halo(C1-C3)alkyl; Y and Y.sup.1 are each independently a monodentate or bidentate ligand; and n is 0 or 1; or a pharmaceutically acceptable salt thereof. [0016] The invention also provides a compound of formula VII: wherein R.sup.1 and R.sup.2 are each independently a cyclopentadienyl ring, wherein any cyclopentadienyl ring may optionally be substituted with one or more (C.sub.1-C.sub.3)alkyl; and R.sup.10-R.sup.13 are each independently H, halo, or (C1-C6)alkyl; or a pharmaceutically acceptable salt thereof. [0017] The invention also provides a pharmaceutical composition comprising a compound of formula II: wherein R and R.sup.1 are each independently H, (C.sub.1-C.sub.3)alkyl, halogen, (C.sub.1-C.sub.3)alkoxy, halo(C1-C3)alkyl, cyano, (C.sub.2-C.sub.6)alkanoyloxy or nitro; X and are each independently a monodentate or bidentate ligand; or no ligand is present on X.sup.1; and Y is a monodentate ligand, or no ligand is present on X.sup.1; and Y is a monodentate ligand or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier. [0018] The invention also provides a pharmaceutical composition comprising a compound of formula III: wherein R.sup.2 and R.sup.3 are each independently H, (C1-C3)alkyl, halogen, (C1-C3)alkoxy, halo(C1-C3)alkyl, cyano, (C.sub.2-C.sub.6)alkanoyloxy or nitro; X.sup.2 and X.sup.3 are each independently a monodentate or bidentate ligand, or no ligand is present on X.sup.3; and Z is O, CH.sub.2, CH.sub.2--CH.sub.2 or CH.dbd.CH; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier; with the proviso that the compound is not [VO(Phen)(H.sub.2O).sub.2](SO.sub.4). [0019] The invention also provides a pharmaceutical composition comprising a compound of formula IV: wherein R.sup.4, R.sup.5 and R.sup.6 are each independently H, (C1-C3)alkyl, halogen, (C1-C3)alkoxy, halo(C1-C3)alkyl, cyano, (C.sub.2-C.sub.6)alkanoyloxy or nitro; X.sup.4 and X.sup.5 are each independently a monodentate or bidentate ligand, or no ligand is present on X.sup.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.sub.2O).sub.2](SO.sub.4). BRIEF DESCRIPTION OF THE FIGURES Continue reading... Full patent description for Vanadium compounds for treating cancer Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Vanadium compounds for treating cancer patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. 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