6,7-Dimethoxyquinazolines and therapeutic use thereof

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C544S283000, C544S293000

Reexamination Certificate

active

06358962

ABSTRACT:

FIELD OF THE INVENTION
This application relates to quinazoline compounds, compositions and therapeutic methods for the treatment of cancers and treatment of allergic disorders by administering quinazoline compounds.
BACKGROUND OF THE INVENTION
Quinazoline compounds have been suggested as useful compounds in the treatment of cell growth and differentiation characterized by activity of the human epidermal growth factor receptor type2 (HER2). See, for example, Myers et.al., U.S. Pat. No. 5,721,237. Some quinazoline derivatives have been suggested as useful as anti-cancer agents for the treatment of specific receptor tyrosine kinase-expressing cancers, especially those expressing epithelial growth factor (EGF) receptor tyrosine kinase. See, for example, Barker et. al., U.S. Pat. No. 5,457,105. It is generally taught that quinazolines exert their anti-tumor effects via tyrosine kinase inhibition. However, while some quinazoline compounds inhibit the growth of brain tumor cells, others with equally potent tyrosine kinase inhibitory activity fail to do so (Naria et.al., 1998,
Clin. Cancer Res.
4:1405-1414; Naria et.al., 1998,
Clin. Cancer Res.
4:2463-2471).
Several tumors expressing EGF receptors are not killed by quinazoline compounds, whereas some tumors not expressing EGF receptors are. Thus, the cytotoxic activity of quinazoline compounds cannot be attributed to the compound's tyrosine kinase inhibitory activity, and particularly not to the compound's ability to inhibit EGF receptor tyrosine kinase. A chemical structure-activity relationship determining the anti-cancer activity of quinazoline derivatives has not been established.
Novel quinazoline compounds may provide potent new therapeutic molecules for the treatment of disorders such as cancers. Methods of using both known and novel quinazoline compounds that employ an understanding of structure-function relationships are needed.
SUMMARY OF THE INVENTION
A series of quinazoline compounds were synthesized and analyzed for therapeutic activities, including anticancer activities, particularly against EGR receptor-negative leukemias. Specific quinazoline compounds of the invention were found to possess potent and specific tyrosine kinase inhibitory activities affecting cell proliferation and survival. Quinazoline compounds of the invention are demonstrated as useful for the treatment of specific tumors, including breast tumors, brain tumors, and leukemias, particularly EGF receptor-negative leukemias, and to be particularly useful in the treatment of multi-drug resistant leukemias.
The invention provides novel quinazoline compounds of formula I as disclosed below, as well as therapeutic methods utilizing these compounds.


REFERENCES:
patent: 4343940 (1982-08-01), Kreighbaum et al.
patent: 4559157 (1985-12-01), Smith et al.
patent: 4608392 (1986-08-01), Jacquet et al.
patent: 4820508 (1989-04-01), Wortzman
patent: 4938949 (1990-07-01), Borch et al.
patent: 4992478 (1991-02-01), Geria
patent: 5457105 (1995-10-01), Barker et al.
patent: 5480883 (1996-01-01), Spada et al.
patent: 5710158 (1998-01-01), Myers et al.
patent: 5712395 (1998-01-01), App et al.
patent: 5721237 (1998-02-01), Myers et al.
patent: 5747498 (1998-05-01), Schnur et al.
patent: 5773476 (1998-06-01), Chen et al.
patent: 5792771 (1998-08-01), App et al.
patent: 5821246 (1998-10-01), Brown et al.
patent: 6184225 (2001-02-01), Thomas et al.
patent: 29 36 705 (1980-03-01), None
patent: 0 566 226 (1993-10-01), None
patent: WO 95/15758 (1995-06-01), None
patent: WO 95/21613 (1995-08-01), None
patent: WO 96/09294 (1996-03-01), None
patent: WO 96/15118 (1996-05-01), None
patent: WO 96/40648 (1996-12-01), None
patent: WO 97/30035 (1997-08-01), None
patent: WO 97/32856 (1997-09-01), None
patent: WO 98/10767 (1998-03-01), None
patent: WO 99/61428 (1999-12-01), None
Bridges, Alexander J.; Zhou, Hairong; Cody, Donna R.; Rewcastle, Gordon W.; McMichael, Amy; Showalter, H. D. Hollis; Fry, David W.; Kraker, Alan J.; Denny, William A., J. Med. Chem., 39(1), 267-76 (English) 1996.*
Parrizas, Marcelina; Gazit, Aviv; Levitzki, Alexander; Wertheimer, Efrat; LeRoith, Derek, Endocrinology, 138(4), 1427-1433 (English) 1997.*
Bridges, A. et al., “Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure-Activity Relationship for Analogues of 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor”,Journal of Medicinal Chemistry, vol. 39, pp. 267-276 (Jan. 19, 1996).
Budesinsky, Z. et al., “A New Synthesis of the Quinazoline Nucleus”,Collection of Czechoslovak Chemical Communications, vol. 37, No. 8, pp. 2779-2785 (Aug. 1972).
Fetter, J. et al., “Electron Deficient Heteroaromatic Ammonioamidates-XVIa, The Synthesis and Photochemistry of Ethyl N-(2-Methyl-4-Methylene-6,7-Methylenedioxy-3,4-Dihydro-3-Quinazolinyl)-N-Phenylcarbamate”,Tetrahedron, vol. 34, pp. 2557-2563 (1978).
Goodman, P. et al., “Role of Tyrosine Kinases in Induction of the c-jun Proto-oncogene in Irradiated B-lineage Lymphoid Cells”,The Journal of Biological Chemistry, vol. 273, No. 28, pp. 17742-17748 (Jul. 10, 1998).
Hatva, E. et al., “Expression of Endothelial Cell-Specific Receptor Tyrosine Kinases and Growth Factors in Human Brain Tumors,”Amer. Journal of Pathology, vol. 146, No. 2, pp. 368-378 (Feb. 1995).
Higashino, T. et al., “Reactions of the anion of quinazoline Reissert compound (3-benzoyl-3, 4-dihydro-4-quinazolinecarbon itrile) with electrophiles”,Chemical&Pharmaceutical Bulletin, vol. 33, No. 3, pp. 950-961 (Mar. 1985).
Ife, R. et al., “Reversible Inhibitors of the Gastric (H+/K+)-ATPase”,Journal of Medicinal Chemistry, vol. 38, No. 14, pp. 2763-2773 (Jul. 7, 1995).
Kubo, K. et al., “A Novel Series of 4-Phenoxyquinolines: Potent and Highly Selective Inhibitors of PDGF Receptor Autophosphorylation”,Bioorganic&Medicinal Chemistry Letters, vol. 7, No. 23, pp. 2935-1940 (Dec. 2, 1997).
Lempert-Sreter, M. et al., “Electron deficient heteroaromatic ammonioamidates,”Chem. Abstract, vol. 93, entry 150203, 1 page (1980).
Malaviya, R et al., “Genetic and Biochemical Evidence for a Critical Role of Janus Kinase (JAK)-3 in Mast Cell-Mediated Type I Hypersensitivity Reactions”,Biochemical and Biophysical Research Communications, vol. 257, No. 3, pp. 807-813 (Apr. 21, 1999).
Miyashita, A. et al., “Catalytic Action of Azolium Salts. II.1)Aroylation of 4-Chloroquinazolines with Aromatic Aldehydes Catalyzed by 1,3-Dimethylbenzimidazolium Iodide,”Chem. Pharm. Bull. vol. 40, No. 1, pp. 43-48 (Jan. 1992).
Miyashita, A. et al., “An Approach to the Synthesis of a Papaverine Analogue Containing a Quinazoline Ring System,”Heterocycles, vol. 40, No. 2 pp. 653-660 (1995).
Miyashita, A. et al., “Several approaches to cyanide ion-catalyzed synthesis of 4-aroyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidines.”Chem. Abstract., vol. 128, entry 270579, 1 page (1998).
Myers, M. R. et al., “The Preparation and SAR of 4-(Anilino), 4-(Phenoxy), and 4-(Thiopenoxy)-Quinazolines: Inhibitors of p56lckand EGF-R Tyrosine Kinase Activity,”Bioorganic&Medicinal Chemistry Letters, vol. 7, No. 4, pp. 417-420 (1997).
Narla, R. K. et al., “4-(3′-Bromo-4′ hydroxylphenyl)-amino-6,7-dimethoxyquinazoline: A Novel Quinazoline Derivative with Potent Cytotoxic Activity against Human Glioblastoma Cells,”Clinical Cancer Research, vol. 4, pp. 1405-1414 (Jun. 1998).
Narla, R. K. et al., Inhibition of Human Glioblastoma Cell Adhesion and Invasion by 4-(4′-Hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131) and 4-(3′-Bromo-4′-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P154),Clinical Cancer Research, vol. 4, No. 10, pp. 2463-2471 (Oct. 1998).
Nomoto, Y. et al., “Studies on Cardiotonic Agents. I. Synthesis of Some Quinazoline Derivatives,”Chem. Pharm. Bull., vol. 38, No. 6, pp. 1591-1595 (1990).
Suzuki, Y. et al., “Carbon-carbon bond cleavage of alpha-hydroxybenzylheteroarenes catalyzed,”Chem. Abstract, vol. 128, entry 230337, 5 pages (1998).
Taylor, E. C. et al., “General procedure for the synthesis of epoxyalkylated and acylated heterocycles

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