Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-01-26
2000-05-16
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544317, A61K 31505, C07D23947
Patent
active
060637870
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention is in the area of medicinal chemistry, and in particular is (-)-(2S,4S)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine (also referred to as (-)-OddC) or its derivative, and its use to treat cancer in animals, including humans.
BACKGROUND OF THE INVENTION
A tumor is an unregulated, disorganized proliferation of cell growth. A tumor is malignant, or cancerous, if it has the properties of invasiveness and metastasis. Invasiveness refers to the tendency of a tumor to enter surrounding tissue, breaking through the basal laminas that define the boundaries of the tissues, thereby often entering the body's circulatory system. Metastasis refers to the tendency of a tumor to migrate to other areas of the body and establish areas of proliferation away from the site of initial appearance.
Cancer is now the second leading cause of death in the United States. Over 8,000,000 persons in the United States have been diagnosed with cancer, with 1,208,000 new diagnoses expected in 1994. Over 500,000 people die annually from the disease in this country.
Cancer is not fully understood on the molecular level. It is known that exposure of a cell to a carcinogen such as certain viruses, certain chemicals, or radiation, leads to DNA alteration that inactivates a "suppressive" gene or activates an "oncogene". Suppressive genes are growth regulatory genes, which upon mutation, can no longer control cell growth. Oncogenes are initially normal genes (called prooncogenes) that by mutation or altered context of expression become transforming genes. The products of transforming genes cause inappropriate cell growth. More than twenty different normal cellular genes can become oncogenes by genetic alteration. Transformed cells differ from normal cells in many ways, including cell morphology, cell-to-cell interactions, membrane content, cytoskeletal structure, protein secretion, gene expression and mortality (transformed cells can grow indefinitely).
All of the various cell types of the body can be transformed into benign or malignant tumor cells. The most frequent tumor site is lung, followed by colorectal, breast, prostate, bladder, pancreas, and then ovary. Other prevalent types of cancer include leukemia, central nervous system cancers, including brain cancer, melanoma, lymphoma, erythroleukemia, uterine cancer, and head and neck cancer.
Cancer is now primarily treated with one or a combination of three types of therapies: surgery, radiation, and chemotherapy. Surgery involves the bulk removal of diseased tissue. While surgery is sometimes effective in removing tumors located at certain sites, for example, in the breast, colon, and skin, it cannot be used in the treatment of tumors located in other areas, such as the backbone, nor in the treatment of disseminated neoplastic conditions such as leukemia.
Chemotherapy involves the disruption of cell replication or cell metabolism. It is used most often in the treatment of leukemia, as well as breast, lung, and testicular cancer.
There are five major classes of chemotherapeutic agents currently in use for the treatment of cancer: natural products and their derivatives; anthracyclines; alkylating agents; antiproliferatives (also called antimetabolites); and hormonal agents. Chemotherapeutic agents are often referred to as antineoplastic agents.
The alkylating agents are believed to act by alkylating and cross-linking guanine and possibly other bases in DNA, arresting cell division. Typical alkylating agents include nitrogen mustards, ethyleneimine compounds, alkyl sulfates, cisplatin, and various nitrosoureas. A disadvantage with these compounds is that they not only attack malignant cells, but also other cells which are naturally dividing, such as those of bone marrow, skin, gastro-intestinal mucosa, and fetal tissue.
Antimetabolites are typically reversible or irreversible enzyme inhibitors, or compounds that otherwise interfere with the replication, translation or transcription of nucleic acids.
Several synthetic nucleosides have been identified tha
REFERENCES:
patent: 4000137 (1976-12-01), Dvonoch et al.
patent: 4336381 (1982-06-01), Nagata et al.
patent: 4861759 (1989-08-01), Misuya et al.
patent: 4879277 (1989-11-01), Mitsuya et al.
patent: 4900828 (1990-02-01), Belica et al.
patent: 4916122 (1990-04-01), Chu et al.
patent: 4963533 (1990-10-01), de Clercq et al.
patent: 4968674 (1990-11-01), Taniyama et al.
patent: 5041449 (1991-08-01), Belleau et al.
patent: 5047407 (1991-09-01), Belleau et al.
patent: 5059690 (1991-10-01), Zahler et al.
patent: 5071983 (1991-12-01), Koszalka et al.
patent: 5151426 (1992-09-01), Belleau et al.
patent: 5179104 (1993-01-01), Chu et al.
patent: 5185437 (1993-02-01), Koszalka et al.
patent: 5204466 (1993-04-01), Liotta et al.
patent: 5210085 (1993-05-01), Liotta et al.
patent: 5215971 (1993-06-01), Datema et al.
patent: 5234913 (1993-08-01), Furman, Jr. et al.
patent: 5248776 (1993-09-01), Chu et al.
patent: 5270315 (1993-12-01), Belleau et al.
patent: 5444063 (1995-08-01), Schinazi
patent: 5466806 (1995-11-01), Belleau et al.
patent: 5700937 (1997-12-01), Liotta et al.
patent: 5817667 (1998-10-01), Chu et al.
Di Marco, M.P. et al. Journal of Chromatography., 645 (1993) pp. 107-114.
Balzarini, J., et al., "Potent and Selective Anti-HTLV-III/LAV Activity of 2',3'-Dideoxycytidinene, the 2',3'-Unsaturated Derivative of 2',3'-Dideoxycytidine," Biochemical and Biophysical Research Communications, 140(2): 735-742 (1986).
Beach, J.W., et al., "Synthesis of Enanatiomerically Pure (2'R,5'S)-(-)-1-[2-(hydroxymethyl)-oathiolan-5-yl] Cytosine as a Potent Antiviral Agent Against Hepatitis B Virus (HBV) and Human Immunodeficiency Virus (HIV)," J. Org. Chem. 57:2217-2219 (1992).
Belleau, B., et al., "Design and Activity of a Novel Class of Nucleoside Analogs Effective against HIV-1," International Conference on AIDS, Montreal, Quebec, Canada, Jun. 4-9, 1989 (Citation).
Bouffard, D.Y., et al., "Kinetic Studies on 2',2'-Diflourordeoxycytidine(gemcitabine) with Purified Human Deoxycytidine Kinase and Cytidine Deaminase," Biochem. Pharmacol. 45(9):1857-1861 (1993).
Carter, et al., "Activities of (-)Carbovir and 3'-Azido-3'-Deoxythymidine Against Human Immunodeficiency Virus In Vitro," Antimicrobial Agents and Chemotherapy, 34(6):1297-1300 (1990).
Chang, C.N., et al., "Biochemical Pharmacology of (+) and (-)-2',3'-Dideoxy-3'Thioacytidine as Anti-Hepatitis B Virus Agents," J. Biol. Chem. 267:22414-22420 (1992).
Chang, Chien-Neng, et al., "Deoxycytidine Deaminase-resistant Stereoisomer is the Active Form of (.+-.)-2,'3'-Dideoxy-3'-thiacytidine in the Inhibition of Hepatitis B Virus Replication," The Journal of Biological Chemistry, 267(20):13938-13942 (1992).
Chang, Chungming et al., "Production of Hepatitis B Virus In Vitro by Transient Expression of Cloned HBV DNA in a Hepatoma Cell Line," The EMBO Journal, 6(3):675-680 (1987).
Chen, Chin-Ho, et al., "Delayed Cytotoxicity and Selective Loss of Mitochondrial DNA in Cells Treated with the Anti-Human Immunodeficiency Virus Compound 2'3'-Dideoxycytidine," The Journal of Biological Chemistry, 264(20):11934-11937 (1989).
Cheng, Y.C., et al., "Human Deoxycytidine Kinase Purification and Characterization of the Cytoplasmic and Mitochondrial Isozymes Derived from Blast Cells of acute Myelocytic Leukemia Patients," Biochim. Biophys. Acta. 481:481-492 (1977).
Chottiner, E.G., "Cloning and Expression of Human Deoxycytidine Kinase cDNA," Proc. Natl. Acad. Sci. USA, 88:1531-1535 (1991).
Chu, C.K., et al., "An Efficient Total Synthesis of 3'-Azido-3'-Deoxythiymidine (AZT) and 3'-Azido-2',3'-Dideoxyuridine (AZDDU, CS-87) from D-Mannitol," Tetrahedron Lett.,29(42):5349 (1988).
Chu, et al., "Comparative Activity of 2',3'-Staturated and Unsaturated Pyrimidine and Purine Nucleosides Against Human Immunodeficiency Virus Type 1 in Peripheral Blood Mononuclear Cells," Biochem. Pharm., 37(19):3543-3548 (1988).
Chu, et al., "Structure-Activity Relationships of Pyrimidine Nucleosides as Antiviral Agents for Human Immunodeficiency Virus Type 1 in Peripheral Blood
Cheng Yung-Chi
Chu Chung K.
Coleman Henry D.
Kessinger Ann M.
Shah Mukund J.
Sudol R. Neil
The University of Georgia Research Foundation Center
LandOfFree
Methods for the treatment of psoriasis and genital warts does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods for the treatment of psoriasis and genital warts, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods for the treatment of psoriasis and genital warts will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-259124