4-anilinoquinazoline derivatives bearing a heteroaryl substitute

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

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

544284, 544293, A01N 4354, C07D40100, C07D23972

Patent

active

059554649

DESCRIPTION:

BRIEF SUMMARY
The invention relates to quinazoline derivatives, or pharmaceutically-acceptable salts thereof, which possess anti-cell-proliferation activity such as anti-cancer activity and are accordingly useful in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said quinazoline derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cell-proliferation effect in a warm-blooded animal such as man.
Many of the current treatment regimes for cell proliferation diseases such as psoriasis and cancer utilize compounds which inhibit DNA synthesis. Such compounds are toxic to cells generally but their toxic effect on rapidly dividing cells such as tumor cells can be beneficial. Alternative approaches to anti-proliferative agents which act by mechanisms other than the inhibition of DNA synthesis have the potential to display enhanced selectivity of action.
In recent years it has been discovered that a cell may become cancerous by virtue of the transformation of a portion of its DNA into an oncogene i.e. a gene which, on activation, leads to the formation of malignant tumor cells (Bradshaw, Mutagenesis, 1986, 1, 91). Several such oncogenes give rise to the production of peptides which are receptors for growth factors. The growth factor receptor complex subsequently leads to an increase in cell proliferation. It is known, for example, that several oncogenes encode tyrosine kinase enzymes and that certain growth factor receptors are also tyrosine kinase enzymes (Yarden et al., Ann. Rev. Biochem., 1988, 57, 443; Larsen et al. Ann. Reports in Med. Chem. 1989, Chpt. 13).
Receptor tyrosine kinases are important in the transmission of biochemical signals which initiate cell replication. They are large enzymes which span the cell membrane and possess an extracellular binding domain for growth factors such as epidermal growth factor (EGF) and an intracellular portion which functions as a kinase to phosphorylate tyrosine amino acids in proteins and hence to influence cell proliferation. Various classes of receptor tyrosine kinases are known (Wilks, Advances in Cancer Research, 1993, 60, 43-73) based on families of growth factors which bind to different receptor tyrosine kinases. The classification includes Class I receptor tyrosine kinases comprising the EGF family of receptor tyrosine kinases such as the EGF, transforming growth factor at (TGF.alpha.), NEU, erbB, Xmrk, DER and let23 receptors, Class II receptor tyrosine kinases comprising the insulin family of receptor tyrosine kinases such as the insulin, IGFI and insulin-related receptor (IRR) receptors and Class III receptor tyrosine kinases comprising the platelet-derived growth factor (PDGF) family of receptor tyrosine kinases such as the PDGF.alpha., PDGF.beta. and colony-stimulating factor 1 (CSF1) receptors. It is known that Class I kinases such as the EGF family of receptor tyrosine kinases are frequently present in common human cancers such as breast cancer (Sainsbury et al., Brit. J. Cancer, 1988, 58, 458; Guerin et al., Oncogene Res., 1988, 3, 21), squamous cell cancer of the lung (Hendler et al., Cancer Cells, 1989, 7, 347), bladder cancer (Neal et al., Lancet, 1985, 366), oesophageal cancer (Mukaida et al., Cancer, 1991, 68, 142), gastrointestinal cancer such as colon, rectal or stomach cancer (Bolen et al., Oncogene Res., 1987, 1, 149), leukaemia (Konaka et al., Cell, 1984, 37, 1035) and ovarian, bronchial or pancreatic cancer (European Patent Specification No. 0400586). As further human tumor tissues are tested for the EGF family of receptor tyrosine kinases it is expected that its widespread prevalance will be established in further cancers such as thyroid and uterine cancer. It is also known that-EGF type tyrosine kinase activity is rarely detected in normal cells whereas it is more frequently detectable in malignant cells (Hunter, Cell, 1987, 50, 823). It has been shown more recently (W J Gullick, Brit. Med. Bull., 1

REFERENCES:
patent: 3266990 (1966-08-01), Lutz et al.
patent: 4343940 (1982-08-01), Kreighbaum et al.
patent: 5373011 (1994-12-01), Haley
patent: 5411963 (1995-05-01), Dreikom et al.
patent: 5571815 (1996-11-01), Schaper et al.
patent: 5747498 (1998-05-01), Schnur et al.
Nomoto et al., CA 112:21004, 1989.
Rewcastle et al., "Tyrosine Kinase Inhibitors. 5. Synthesis and 4-(Phenylamino)quinazolines as Potent Adenosine 5'-Triphosphate Binding Site Inhibitors of the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor," J.Med.Chem. 1995, vol. 38, pp. 3482-3487.
Burke, Jr., "Protein-tyrosine kinase inhibitors," Drugs of the Future 1992, vol. 17(2), pp. 119-131.
Spence, "Inhibitors of Tyrosine Kinase Activity as Anticancer Therapeutics: Recent Developments," Expert Opinion in Therapeutic Patents, Jan. 1993, Patent Update, Anticancers, etc., pp. 3-9, Current Drugs Ltd ISSN 0962-2594,.
Spada et al., Small molecule inhibitors of tyrosine Kinase activity, Exp.Opin.Ther.Patents (1995), 5(8):805-817, Patent Update, Oncologic, Endocrine & Metabolic, Ashley Publications Ltd ISSN 1354-3776.
Bridges, "The current status of tyrosine kinase inhibitors: do the diarylamine inhibitors of the EGF receptor represent a new beginning?," Exp.Opin.Ther.Patents (1995), 5(12):1245-1257, Editorial Oncologic, Endocrine & Metabolic, 1995 Ashley Publications Ltd ISSN 1354-3776.
Traxler et al., "Recent advances in protein tyrosine kinase inhibitors," Drugs of the Future 1995, vol. 20(12,pp. 1261-1274.
Iyer et al., "Studies in Potential Amoebicides: Part III-Synthesis of .sub.4 -Substituted Amino-8-Hydroxy) Quinazolines & .sub.3 -Substituted 8-Hydroxy(&8-Methoxy)-.sub.4 -Quinazolones," J.Sci.Indust.Res., vol. 15C, Jan. 1956, pp. 1-7.
Kobayashi, Derwent Abstract 82-87007, vol. 6, No. 244, Dec. 1982, JP 57-144266, Sep. 1982, "4-Anilinoquinazoline Derivative, its Preparation and Analgesic and Antiphlogistic Agent Containing Said Derivative as Active Component".
Sankyo and Ube, Derwent Abstract 81-28290, JP 56-20577, Feb. 1981, "4-(N-alkyl:anilino) quinazoline derivs . . . having analgesic and antiinflammatory actions".
Kyorin, Derwent Abstract 84-53835, JP 59-13765, Jan. 1984, "2-(4-Quinazolinyl)amino benzoic acid derivs . . . having analgesic and antiinflammatory activities".
Li et al., Chem.Abs., vol. 92:76445u, 1980, p.674-675.
Lin et al., Chem.Abs., vol. 96:122728w, 1982, p. 695.
Buchdunger et al., "4,5-Dianilinophthalimide: A protein-tyrosine kinase inhibitor with selectivity for the epidermal growth factor receptor signal transduction pathway and potent in vivo antitumor activity," Proc.Natl.Acad.Sci., USA, vol. 91, pp. 2334-2338, Mar. 1994, Applied Biological Sciences.
Trinks et al., "Dianilinophthalimides: Potent and Selective, ATP-Competitive Inhibitors of the EGF-Receptor Protein Tyrosine Kinase," J.Med. Chem. 1994, vol. 37, pp. 1015-1027.
Maguire et al., "A New Series of PDGF Receptor Tyrosine Kinase Inhibitors: 3-Substituted Quinoline Derivatives," J.Med.Chem. 1994, vol. 37, pp. 2129-2137.
Dolle et al., "5,7-Dimethoxy-3-(4-pyridinyl)quinoline Is a Potent and Selective Inhibitor of Human Vascular .beta.-Type Platelet-Derived Growth Factor Receptor Tyrosine Kinase," J.Med.Chem. 1994, vol. 37, pp. 2627-2629.
Bridges et al., "Enantioselective Inhibition of the Epidermal Growth Factor Receptor Tyrosine Kinase by 4-(.alpha.-Phenethylamino)quinazolines," Biorganic & Medicinal Chemistry, vol. 3, No. 12, pp. 1651-1656, 1995.
Ward et al., "Epidermal Growth Factor Receptor Tyrosine Kinase--Investigation of Catalytic Mechanism, Structure-Based Searching and Discovery of a Potent Inhibitor," Biochem.Pharmacology, vol. 48, No. 4, pp. 659-666 (1994).
Agrawal, "Studies on Potential Filaricides: Part XI" Chemical Abstracts, vol. 95, No. 1, 1981, Abstract No. 7199s, pp. 682-683; see abstract in Indian J. Chem. Sect. B, vol. 19B, No. 12, 1980, India, pp. 1084, 1087.
Connolly, et al., "Human Vascular Permeability Factor," J.Bio.Chem., vol. 264, No. 33, Nov. 1989, pp. 20017-20024.
Cullinan-Bov

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

4-anilinoquinazoline derivatives bearing a heteroaryl substitute does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with 4-anilinoquinazoline derivatives bearing a heteroaryl substitute, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 4-anilinoquinazoline derivatives bearing a heteroaryl substitute will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-80465

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.