Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-06-27
1998-08-11
Lambkin, Deborah C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514423, 514445, 514448, 514471, 514575, 514613, 514618, 514621, 546118, 5483047, 548530, 549 72, 549 77, 549487, 549 66, 562621, 564161, 564182, 564189, A61K 3144, A61K 3140, C07D30702, C07C23300
Patent
active
057927766
ABSTRACT:
Disubstituted tetrahydrofurans, tetrahydrothiophenes, pyrrolidines and cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i. e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase.
A method to treat disorders mediated by PAF and/or leukotrienes is also disclosed, that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.
REFERENCES:
patent: 2690988 (1954-10-01), Jones et al.
patent: 4166452 (1979-09-01), Generales, Jr.
patent: 4256108 (1981-03-01), Theeuwes
patent: 4265874 (1981-05-01), Bonsen et al.
patent: 4522811 (1985-06-01), Eppstein et al.
patent: 4539332 (1985-09-01), Biftu et al.
patent: 4595693 (1986-06-01), Biftu et al.
patent: 4604407 (1986-08-01), Haslanger et al.
patent: 4656190 (1987-04-01), Shen et al.
patent: 4757084 (1988-07-01), Biftu et al.
patent: 4841968 (1989-06-01), Dunn et al.
patent: 4845129 (1989-07-01), Anderson et al.
patent: 4871756 (1989-10-01), Gillard et al.
patent: 4873259 (1989-10-01), Summers, Jr. et al.
patent: 4876346 (1989-10-01), Musser et al.
patent: 4891363 (1990-01-01), Nakamura et al.
patent: 4910206 (1990-03-01), Houlihan
patent: 4916145 (1990-04-01), Tilley et al.
patent: 4959361 (1990-09-01), Walser
patent: 4987132 (1991-01-01), Mase et al.
patent: 4992428 (1991-02-01), Houlihan et al.
patent: 4996203 (1991-02-01), Biftu et al.
patent: 5001123 (1991-03-01), Biftu et al.
patent: 5037853 (1991-08-01), Brooks et al.
patent: 5047420 (1991-09-01), Graham et al.
patent: 5110831 (1992-05-01), Magolda et al.
patent: 5112848 (1992-05-01), Brooks et al.
patent: 5169854 (1992-12-01), Brooks et al.
patent: 5175183 (1992-12-01), Brooks et al.
patent: 5183818 (1993-02-01), Brooks et al.
patent: 5187192 (1993-02-01), Brooks et al.
patent: 5234950 (1993-08-01), Edwards et al.
patent: 5244896 (1993-09-01), Borcherding et al.
patent: 5288751 (1994-02-01), Brooks et al.
patent: 5296494 (1994-03-01), Lavrelle et al.
patent: 5326787 (1994-07-01), Brooks et al.
patent: 5334616 (1994-08-01), Mueller et al.
patent: 5344843 (1994-09-01), Guthrie et al.
patent: 5358938 (1994-10-01), Cai et al.
patent: 5420164 (1995-05-01), Mishina et al.
patent: 5434151 (1995-07-01), Cai et al.
patent: 5463083 (1995-10-01), Biftu et al.
patent: 5561134 (1996-10-01), Spada et al.
Leonard et al, "Amides of 1-methyl-5-(3,4-dimethoxyphenyl)pyrolidine-2 emboxylic acid", Cai :70485 (1969).
Bartroli, J., "Design of Potent Linear PAF Antagonists," J. Med. Chem., vol. 34 (1991) pp. 3328-3334.
Biftu, T., et al., "Confirmation and Activity of Tetrahydrofuran Lignans and Analogues as Specific Platelet Activating Factor Antagonists," J. Med. Chem. vol., 29, No. 10 (1986) pp. 1917-1921.
Caricellar, E., et al., "4-Substituted 2-Alkoxytetrahydro-furans as Potent and Long-Lasting PAF Antagonists," J. Med. Chem., vol. 35 (1992) pp. 676-683.
Corey, F. J., et al., "Dual Binding Modes to the Receptor for Platelet Activating Factor (PAF) of Anti-PAF Trans-2,5-Diarylfurans," Tetrahedron Letters, vol. 29, No. 24 (1988) pp. 2899-2902.
Crawley, G.C., "Methoxytetrahydropyrans. A New Series of Selective and Orally Potent 5-Lipoxygenase Inhibitors," J. Med. Chem., vol. 35, No. 14 (1992) pp. 2600-2609.
Feinmark, S. J., "Leukotriene C Biosynthesis during Polymorphonuclear Leukocyte-Vascular Cell Interactions," Methods in Enzymology, vol. 187, pp. 559-560, (1990).
Graham, D.W., et al., "1.3-Diarylcyclopentanes: A New Class of Potent PAF Receptor Antagonists,", 197.sup.th ACS National Meeting, Division of Medicinal Chemistry, Poster No. 25, Dallas, Texas (Apr., 1989).
Guthrie, R.W., et al., "Propenyl Carboxamide Derivatives As Antagonists of Platelet Activating Factor," J. Med. Chem., vol. 33 (1990) pp. 2856-2864.
Hwang, S., "Specific Receptors of Platelet-Activating Factor, Receptor Heterogeneity, and Signal Transduction Mechanisms," J. Lipid Mediators, vol. 2 (1990) pp. 123-158. Antagonists," Drugs of the Future, vol. 14, No. 9 (1989) pp. 891-898.
McColl, S.R., "Determination of 5-Lipoxygenase Activity in Human Polymorphonuclear Leukocytes Using High-Performance Liquid Chromatography," J. Chromatography, vol. 378 (1986) pp. 44-449.
Musser, J.H., et al., "5-Lipoxygenase: Properties, Pharmacology, and the Quinolinyl(bridge)aryl Class of Inhibitors," J. Med. Chem., vol. 35, No. 14 (1992) pp. pp. 2502-2524.
O'Donnell, M., et al., "Comparison of the Pulmonary Pharmacology of Leukotrienes and PAF: Effects of their Antagonists," Therapeutic Approaches to Inflammatory Diseases Proceedings of the Fourth International Conference of the Inflammatory Research Association, Oct. 23-27, 1988, White Haven, Pennsylvania, p. 169.
Ogiso, A., et al., "The Structure of Futoenone, A Novel Spiro-Cyclohexadienone Derivative," Tetrahedron Letters, No. 16, (1968) pp. 2003-2008.
Ogiso, A., et al., "The Structure and Total Synthesis of Futoenone, a Constitute of Piper futokadzura SIEB. et ZUCC.," Chem. Pharm. Bull., vol. 18, No. 1, (1970) pp. 105-114.
Page, C., et al., "PAF: New Antagonists: New Roles in Diseases and a Major Role in Reproductive Biology," 3rd International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 8-12, 1989.
Ponpipom, M.M., et al., "Structure-Activity Relationships of Kadsurenone Analogues," J. Med. Chem., vol. 30 (1987) pp. 136-142.
Ponpipom, M.M., et al., "(.+-.)-TRANS-2-(3-Methylsulfonyl-4-Propoxyphenyl)-5-(3,4,5-Trimethoxyphen yl)Tetrahydrofuran (L-659,989), A Novel, Potent PAF Receptor Antagonist," Biochemical and Biophysical Research Communications, vol. 150, No. 3 (1988) pp. 1213-1220.
Shen, T.Y., "Characterization of a Platelet-Activating Factor Receptor Antagonist Isolated from Halifenteng (Piper futokadsura): Specific Inhibition of in vitro and in vivo Platelet-Activating Factor-Induced Effects," Proc. Natl. Acad. Sci. USA, vol. 82, (Feb. 1985) pp. 672-676.
Shen, T.Y., et al., "The Chemical and Biological Properties of PAF Agonists, Antagonists, and Biosynthetic Inhibitors," Platelet-Activating Factor and Related Lipid Mediators, Plenum Press, New York, NY, pp. 153-190, (1986).
Weber, K.H., et al., "Hetrazepines as Antagonists of Platelet Activating Factor," Medicinal Research Reviews, vol. 9, No. 1 (Jan.-Mar. 1989) pp. 181-218.
Communication dated Mar. 4, 1997 in European Patent App. No. 95907972.4.
Backvall, et al., "A Stereocontrolled Organopalladium Route to 2,5-Disubstituted Pyrrolidine Derivatives. Application to the Synthesis of a Venom Alkaloid of the Ant Species Monomorium latinode," J. Org. Chem., 55:826-831 (1990).
Biftu, T., et al., Abstr. of 6th Int. Conf. on Prostaglandins and Related Compounds, Florence, Italy, p. 302 (Jun. 3-6, 1986).
Bowles, et al., A Convenient Preparation of Cyclic Ether Acetals Mediated by Trifluoroacetic Anhydride, Synlett, pp. 111-112 (1993).
Carter, et al., "5-Lipoxygenase Inhibitory Activity of Zileuton," J. of Pharmacol. and Exp. Thera., 256(3);929-937 (1991).
Danyoshi et al., "Pyrrolidine Derivatives as Inhibitors of Platelet Aggregation Induced by Platelet Activating Factor," Chem. Pharm. Bull., 37(7):1969-1970 (1989).
Erez, et al., "Narcotic Antagonistic Potency of Bivalent Ligands Which Contain Beta-Naltrexamine. Evidence for Bridging between Proximal Recognition Sites," J. of Med. Chem., 25(7):847-849 (1982).
Foye, (Editor) "Bioisosterism," Principles of Med. Chem., Second Edition, pp. 80-81 (Lea & Febiger, Philadelphia, 1981).
Goldstein, et al., "Dual Inhibitors of Platelet Activating Factor and 5-Lipoxygenase. I., 2,40Diaryl-1,3-dithiolanes," Med. Chem. Res., 2:443-450 (1992).
Goldstein, et al., "Dual Inhibitors of Platelets Activating Factor and 5-Lipoxygenase. II. Novel 2,4-Diaryl-1,3-dithiolanes with Iron-Chelating Functiona
Biftu Tesfaye
Cai Xiong
Hussoin Sajjat
Scannell Ralph
Cytomed, Inc.,
Lambkin Deborah C.
LandOfFree
Compounds and methods for the treatment of cardiovascular, infla does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compounds and methods for the treatment of cardiovascular, infla, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compounds and methods for the treatment of cardiovascular, infla will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-389275