Use of nitric oxide releasing compounds as hypoxic cell radiation sensitizers

Patent 5650442 Issued on July 22, 1997. Estimated Expiration Date:

October 7, 2014. Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.

Abstract Claims Description Full Text

Patent References

Stabilized nitric oxide - primary amine complexes useful as cardiovascular agents
Patent #: 4954526
Issued on: 09/04/1990
Inventor: Keefer

Anti-hypertensive compositions of secondary amine-nitric oxide adducts and use thereof
Patent #: 5039705
Issued on: 08/13/1991
Inventor: Keefer, et al.

Complexes of nitric oxide with polyamines
Patent #: 5155137
Issued on: 10/13/1992
Inventor: Keefer, et al.

Antihypertensive compositions and use thereof
Patent #: 5212204
Issued on: 05/18/1993
Inventor: Keefer, et al.

Method of preventing NMDA receptor complex-mediated neuronal damage Patent #: 5234956
Issued on: 08/10/1993
Inventor: Lipton

Inventors

Assignee

The United States of America as represented by the Administrator of the

Application

No. 319888 filed on 10/07/1994

US Classes:

514/611, Nitrosamines (i.e., compounds containing nitroso bonded directly to amino nitrogen)514/149, Azoxy DOAI514/238.2, Chalcogen attached directly to the nitrogen by nonionic bonding514/255.01, Nitrogen or -C(=X)-, wherein X is chalcogen, bonded directly to the piperazine ring514/315, Piperidines514/319, The additional ring is one of the cyclos in a polycyclo ring system514/329, Nitrogen attached directly to the piperidine ring by nonionic bonding514/332, Plural six-membered hetero rings consisting of one nitrogen and five carbon atoms514/357, Nitrogen attached indirectly to the six-membered hetero ring by nonionic bonding514/426, Nitrogen bonded directly to the five-membered hetero ring by nonionic bonding514/492, Heavy metal containing DOAI514/494, Zinc514/499, Copper514/558, Higher fatty acid or salt thereof514/563, RC(=O)N containing (i.e., carboxamide) (R is C or H)514/564, Plural nitrogens nonionically bonded514/579, Nitrogen containing other than solely as a nitrogen in an inorganic ion of an addition salt, a nitro or a nitroso DOAI514/610, Nitramines (i.e., compounds containing nitro bonded directly to amino nitrogen)514/645, Nitroxides, oxyamines or hydroxylamines (i.e., N-O or N-OH)514/647, Amino nitrogen and a ring bonded directly to the same ring and any other amino nitrogen in the compound is bonded directly to one of the rings514/649, Amino nitrogen attached to aryl ring or aryl ring system by an acyclic carbon or acyclic chain600/1RADIOACTIVE SUBSTANCE APPLIED TO BODY FOR THERAPY

Examiners

Primary: Dees, Jose G.
Assistant: Cebulak, Mary C.

Attorney, Agent or Firm

Leydig, Voit & Mayer, Ltd.

Foreign Patent References

WO93/07114 WO. 04/25/1993
WO93/20088 WO. 10/25/1993
WO93/20806 WO. 10/25/1993

International Classes

A61K 031/13
A61K 031/44
A61K 031/495
A61K 031/445
645
649
647

Abstract

The present invention provides a method for sensitizing hypoxic cells in a tumor to radiation, wherein nitric oxide is delivered to target hypoxic cells through the administration of a nitric oxide-containing compound that spontaneously releases nitric oxide under physiological conditions without requiring the presence of oxygen. Also provided are methods of protecting noncancerous cells or tissues in a mammal from radiation, sensitizing cancerous cells in a mammal to chemotherapeutic agents, and protecting noncancerous cells or tissues in a mammal from chemotherapeutic agents, all by administration of the same compounds.

Other References

Song et al., Int. J. Rad. Oncol. Biol. Phys., 30 (Supp. 1), p. 208 (1994)
Adams et al., "Electron-Affinic Sensitization," Radiation Research, 67:9-20 (1976)
Andrade et al., "Inhibitors of Nitric Oxide Synthase Selectively Reduce Flow in Tumour-Associated Neovasculature," Br. J. Pharmacol, 107:1092-1095 (1992)
Bedford et al., "Threshold Hypoxia: Its Effect on the Survival of Mammalian Cells Irradiated at High and Low Dose-Rates," Br. J. Radiol., 39:896-900 (1966)
Bohn et al., "Oxygen and Oxidation Promote the Release of Nitric Oxide from Sydnonimines," Journal of Cardiovascular Pharmacology, 14(Suppl. 11):S6-S12 (1989)
Coleman et al., "Phase I Trial of the Hypoxic Cell Radiosensitizer SR-2508: The Results of the Five to Six Week Drug Schedule," I.J. Radiation Oncology Biol. Phys., 12:1105-1108 (1986)
DeGraff et al., "Evaluation of Nitroimidazole Hypoxic Cell Radiosensitizers in a Human Tumor Cell Line High in Intracellular Glutathione," I.J. Radiation Oncology Biol. Phys., 16:1021-1024 (1989)
Feelisch et al., "On the Mechanism of NO Release from Sydnonimines," Journal of Cardiovascular Pharmacology, 14(Suppl. 11):S13-S22 (1989)
Feelisch, M., "The Biochemical Pathways of Nitric Oxide Formation from Nitrovasodilators: Appropriate Choice of Exogenous NO Donors and Aspects of Preparation and Handling of Aqueous NO Solutions," J. Cardiovasc. Pharmacol. 17(Suppl. 3):S25-S33 (1991)
Gatenby et al., "Oxygen Distribution in Squamous Cell Carcinoma Metastases and its Relationship to Outcome of Radiation Therapy," I.J. Radiation Oncology Biol. Phys., 14:831-838 (1988)
Hall et al., "Extreme Hypoxia; Its Effect on the Survival of Mammalian Cells Irradiated at High and Low Dose-Rates," Br. J. Radiol., 39:302-307 (1966)
Hall, Eric J., "The Oxygen Effect and Reoxygenation," Radiobiology for the Radiologist, 4th Ed.:133-164 (1994)
Howard-Flanders, "Effect of Nitric Oxide on the Radiosensitivity of Bacteria," Nature, 180:1991-1192 (1957)
Hrabie et al., "New Nitric Oxide-Releasing Zwitterions Derived from Polyamines," J. Org. Chem., 58:1472-1476 (1993)
Ignarro, Louis J., "Biosynthesis and Metabolism of Endothelium-Derived Nitric Oxide," Annu. Rev. Pharmacol, Toxicol, 30:535-60 (1990)
Keefer et al., "Complexes of Nitric Oxide with Nucleophiles as Agents for the Controlled Biological Release of Nitric Oxide," Biology of Nitric Oxide, 2, Enzymology, Biochemistry, Immunology, pp. 153-156, Moncada et al., eds. Portland Press. Chapel Hill, NC (1992)
Maragos, et al., "Complexes of NO with Nucleophiles as Agents for the Controlled Biological Release of Nitric Oxide, Vasorelaxant Effects," J. Med. Chem., 34:3242-3247 (1991)
Maragos et al., "Nitric Oxide/Nucleophile Complexes Inhibit the In Vitro Proliferation of A375 Melanoma Cells via Nitric Oxide Release," Cancer Research, 53:564-568 (1993)
Morley et al., "Mechanism of Vascular Relaxation Induced by the Nitric Oxide (NO)/Nucleophile Complexes, a New Class of NO-Based Vasodilators," Journal of Cardiovascular Pharmacology, 21:670-676 (1993)
Murayama et al., "Radiosensitization of Hypoxic HeLa S3 Cells In Vitro by a New Type of Radiosensitizer: Spermine and Spermidine Amides with Nitro Groups," Int. J. Radiat. Biol., 44(5):497-503 (1983)
Mitchell et al., "Cellular Glutathione Depletion by Diethyl Maleate or Buthionine Sulfoximine; No Effect of Glutathione Depletion on the Oxygen Enhancement Ratio," Radiation Research, 96:422-428 (1983)
Phillips et al., "Promise of Radiosensitizers and Radioprotectors in the Treatment of Human Cancer," Cancer Treatment Reports, 68(1):291-302 (1984)
Phillips et al., "Variation in Sensitizing Efficiency for SR 2508 In Human Cells Dependent on Glutathione Content," I.J. Radiation Oncology Biol. Phys., 12:1627-1635 (1986)
Powers-Tolmach, "A Multicomponent X-Ray Survival Curve for Mouse Lymphosarcoma Cells Irradiated In Vivo," Nature, 197:710-711 (1963)
Russo et al., "The Effects of Cellular Glutathione Elevation on the Oxygen Enhancement Ratio," Radiation Research, 103:232-239 (1985)
Siemann et al., "Characterization of Radiation Resistant Hypoxic Cell Subpopulations In KHT Sarcomas. (ii) Cell Sorting," Br. J. Cancer, 58:296-300 (1988)
Stamler et al., "S-Nitrosylation of Proteins with Nitric Oxide: Synthesis and Characterization of Biologically Active Compounds," Proc. Natl. Acad. Sci. USA, 89:444-448 (1992)
Stamler et al., "Nitric Oxide Circulates in Mammalian Plasma Primarily as an S-Nitroso Adduct of Serum Albumin," Proc. Natl. Acad. Sci. USA, 89:7674-7677 (1992)
Thomlinson et al., "The Histological Structure of Some Human Lung Cancers and the Possible Implications for Radiotherapy," British Journal of Cancer, IX(4):539-549 (1955)
von Sonntag, C., "The Chemical Basis of Radiation Biology," The Chemical Basis of Radiation Biology, Taylor and Francis, eds., London (1987)
Wink et al., "DNA Deaminating Ability and Genotoxicity of Nitric Oxide and Its Progenitors," Science, 254:1001-1003 (1991)
Wood et al., "Modification of Energy Metabolism and Radiation Response of A Murine Tumour by Changes in Nitric Oxide Availability," Biochemical and Biophysical Research Communications, 192(2):505-510 (1993