Organic compounds -- part of the class 532-570 series – Organic compounds – Four or more ring nitrogens in the bicyclo ring system
Reexamination Certificate
2005-03-01
2010-10-19
Balasubramanian, Venkataraman (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Four or more ring nitrogens in the bicyclo ring system
C514S243000, C514S231500, C544S112000
Reexamination Certificate
active
07816521
ABSTRACT:
The compound 3-ethyl-6-[3-(4-morpholinyl)propoxy]-1,2,4-benzotriazine 1,4-dioxide and pharmacologically acceptable salts thereof. A method of treating cancer in a subject is also described in which 3-ethyl-6-[3-(4-morpholinyl)propoxy]-1,2,4-benzotriazine 1,4-dioxide or a pharmacologically acceptable salt thereof is administered to tumor cells in a hypoxic environment. Also described is a method of radiosensitising in a subject tumor cells of solid tumors in hypoxic conditions by administering to the subject a pharmaceutical composition containing 3-ethyl-6-[3-(4-morpholinyl)propoxy]-1,2,4-benzotriazine 1,4-dioxide or a pharmacologically acceptable salt thereof in an amount sufficient to produce radiosensitivity in the tumor cells, and subjecting the tumor cells to radiation. A pharmaceutical composition is additionally provided containing a therapeutically effective amount of 3-ethyl-6-[3-(4-morpholinyl)propoxy]-1,2,4-benzotriazine 1,4-dioxide or a pharmacologically acceptable salt thereof and a pharmaceutically acceptable excipient, adjuvant, carrier, buffer or stabiliser.
REFERENCES:
patent: 3991189 (1976-11-01), Seng et al.
patent: 4027022 (1977-05-01), Seng et al.
patent: 5175287 (1992-12-01), Lee et al.
patent: 2002/0103200 (2002-08-01), Lee et al.
patent: 2003265023 (2004-04-01), None
patent: 272 591 (1989-10-01), None
patent: 0 649 658 (1995-04-01), None
patent: WO 89/08647 (1989-09-01), None
patent: WO 91/04028 (1991-04-01), None
patent: WO 97/11699 (1997-04-01), None
patent: WO 2004/026846 (2004-04-01), None
Bussink et al., Radiotherapy and Oncology, 67, 3-15, 2003.
Cecil Textbook of Medicine, edited by Bennet, J.C., and Plum F., 20th edition,vol. 1, 1004-1010, 1996.
Freshney et al.,Culture of Animal Cells, A Manual of Basic Technique, Alan R. Liss, Inc., 1983, New York, p. 4.
Dermer et al., Bio/Technology, 1994, 12:320.
Cohen et al., Current Opinion in Chemical Biology, 3,459-465, 1999.
Golub et al., Science, 286, 531-537, 1999.
CA 138:304247 & Tetrahedron Letters, 2002, vol. 43(52, pp. 9569-9571, M.P. Hay et al; “New and Versatile Synthesis of 3-alkyl- and 3-aryl-1,2,4-benzotriazine 1,4-dioxides: preparation of the bioreductive cytotoxins SR 4895 and SR 4941”; Registry No. 71503-85-0.
CA 129:339530 & Anti-cancer drug design, 1998, vol. 13(6), pp. 575-592, A.B. Kelson et al; “1,2,4-benzotriazine 1,4-dioxides. An important class of hypoxic cytotoxins with antitumor activity”; Registry Nos. 71503-85-0, 166182-18-9, 215535-68-5, 215535-71-0.
CA 138:130592 & Journal of Medicinal Chemistry, 2003, vol. 46(1), pp. 169-182, M.P. Hay et al; “Structure-activity relationships of 1,2,4-benzotriazine 1,4-dioxides as hypoxia-selective analogues of tirapazamine”; Registry No. 50476-99-8.
International Journal of Radiation Oncology Biol. Phys. 1992, vol. 22, No. 4, pp. 701-705, A.I. Minchinton et al; “Second-generation 1,2,4-benzotriazine 1,4-di-N-oxide bioreductive anti-tumor agents: Pharmacology and activity in vitro and in vivo”.
Supplementary European Search Report; International Application No. EP 05 72 2109, dated Oct. 5, 2009 (2 pgs).
Hay, M.P., et al; Hypoxia-Selective 3-Alkyl 1,2,4-Benzotriazine 1,4-Dioxides: The Influence of Hydrogen Bond Donors on Extravascular Transport and Antitumor Activity;J. Med. Chem..; vol. 50, pp. 6654-6664 (2007).
Shinde, S.S., et al; Oxidation of 2-Deoxyribose by Benzotriazinyl Radicals of Antitumor 3-Amino-1,2,4-benzotriazine 1,4-Dioxides;J. Am. Chem. Soc.; vol. 126; pp. 7865-7874 (2004) XP-002547140.
Denny William Alexander
Hay Michael Patrick
Hicks Kevin Owen
Pchalek Karin
Pruijn Frederik
Auckland Uniservices Limited
Balasubramanian Venkataraman
Nixon & Vanderhye
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