Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-06-07
1997-10-28
Raymond, Richard L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
549 77, 549 68, 549493, 549487, 549480, 514445, 514447, 514471, 514472, 514473, C07D33322, C07D30702, A61K 3138, A61K 3134
Patent
active
056819668
ABSTRACT:
Enantiomerically enriched 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.
It has been determined that 5-lipoxygenase activity, oral availability, and stability in vivo (for example, glucuronidation rate) can vary significantly among the optical isomers of the disclosed compounds.
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: 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: 5326787 (1994-07-01), Brooks et al.
patent: 5334616 (1994-08-01), Brooks 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.
Backvall, et al., "A Stereocontrolled Organopalladium Route to 2,5-Disubstituted Pyrroline Derivatives. Application to the Synthesis of a Venom Alkaloid of the Ant Species Monomorium latinode," J. Org. Chem., 55:826-831(1990).
Bartroli, J., "Design of Potent Linear PAF Antagonists," J. Med. Chem., 34:3328-3334 (1991).
Biftu, T., et al., Abstr. of 6th Int. Conf. on Prostaglandins and Related Compounds, Florence, Italy, p. 302 (Jun. 3-6, 1986).
Biftu, T., et al., "Confirmation and Activity of Tetrahydrofuran Lignans and Analogues as Specific Platelet Activating Factor Antagonists," J. Med Chem., 29(10):1917-1921 (1986).
Bowles, et al., "A Convenient Preparation of Cyclic Ether Acetals Mediated by Trifluoroacetic Anhydride," Synlett, pp. 111-112 (1993).
Carlcellar, E., et al, "4-Substituted 2-Alkoxytetrahydrofurans as Potent and Long-Lasting PAP Antagonists," J. Med. Chem., 35(4):676-683 (1992).
Carter, et al., "5-Lipoxygenase Inhibitory Activity of Zileuton," J. of Pharmacol. and Exp. Thera., 256(3);929-937 (1991).
Corey, E.J. et al., "Dual Binding Modes to the Receptor for Platelet Activating Factor (PAF) of Anti-PAF Trans-2,5-Diarylfurans," Tetrahedron Letters, 29(24):2899-2902 (1988).
Crawley, G.C., "Methoxytetrahydropyrans. A New Series of Selective and Orally Potent 5-Lipoxygenase Inhibitors," J. Med. Chem., 35(14):2600-2609 (1992).
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).
Feinmark, S.J., "Leukotriene, C.sub.4 Biosynthesis During Polymorphonuclear Leukocyte-Vascular Cell Interactions," Methods in Enzymology, Murphy and Fitzpatrick, eds., Academic Press, Inc., Harcourt Brace Jovanovich, publishers, New York, NY, vol. 187, pp. 559-560 (1990).
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 Platelet Activating Factor and 5-Lipoxygenase. II. Novel 2,4-Diaryl-1,3-dithiolanes with Iron-Chelating Functionalities," Med. Chem. Res., 2:451-456 (1992).
Graham, D.W., et al., "1,3-Diarylcyclopentanes: A New Class of Potent PAF Receptor Antagonists," 197th ACS National Meeting, Division of Medicinal Chemistry, poster No. 25, Dallas, Texas (Apr. 9-14, 1989).
Guthrie, R.W., et al., "Propenyl Carboxamide Derivatives As Antagonists of Platelet Activating Factor," J. Med. Chem., 33:2856-2864 (1990).
Hwang, S., "Specific Receptors of Platelet-Activating Factor, Receptor Heterogeneity, and Signal Transduction Mechanisms," J. Lipid Mediators, 2:123-158 (1990).
Hwang, S., et al., "Trans-2, 5-bis-(3,4,5-trimethoxyphenyl)tetrahydrofuran," Journal of Biological Chemistry, 260(29): 15639-15645 (1985).
Hwang, S., et al., "Biochemical and Pharmacological Charactgerization of L-659, 989: An Extremely Potent, Selective and Competitive Receptor Antagonist of Platelet-Activating Factor," J. Pharmacol. Ther., 246(2):534-541 (1988).
Ikeda et al., "Preparation of Hydroxamic Acid and N-Hydroxyurea Derivatives and Their Use as Lipoxygenase Inhibitors," Chemical Abstracts, vol. 118, Abstract No. 59426 (1993). Antagonists," Drugs of the Future, 14(9):891-898 (1989).
McColl, S.R., "Determination of 5-Lipoxygenase Activity in Human Polymorphonuclear Leukocytes Using High-Performance Liquid Chromatography," J. Chromatography, 378:444-449 (1986).
Musser, J.H., et al., "5-Lipoxygenase: Properties, Pharmacology, and the Quinolinyl(bridged)aryl Class of Inhibitors," J. Med Chem., 35(14):2502-2524 (1992).
O'Donnell, M., et al., "Comparison of the Pulmonary Pharmacoogy of Leukotrienes and PAF: Effects of Their Antagonists," Therapeutic Approaches to Inflammatory Diseases, Proceedings of the Fourth International Conference of the Inflammation Research Association, pp. 169-193; White Haven, Pennsylvania (Oct. 23-27, 1988).
Ogiso, A., et al., "The Structure of Futoenone, A Novel Spiro-Cyclohexadienone Derivative," Tetrahedron Letters, No. 16, pp. 2003-2008 (1968).
Ogiso, A., et al., "The Structure and Total Synthesis of Futoenone, a Constitute of Piper futokadzura SIEB. et ZUCC.sup.1) " Chem. Pharm. Bull., 18(1):105-114 (1970).
Page, C. et al., "PAR: New Antagonists, New Roles in Diseases and a Major Role in Reproductive Biology," Trends in Pharmacol. Sci., pp. 256-257 (1989).
Ponpipom, M.M., et al., "Structure-Activity Relationships of Kadsurenone Analogues," J. Med. Chem., 30:136-142 (1987).
Ponpipom, M.M., et al., "(.+-.)-TRANS-2-(3-Methoxy-5-Methylsulfonyl-4-Propoxyphenyl)-5-(3,4,5-Trim ethoxyphenyl) Tetrahydrofuran (L-659,989), A Novel, Potent PAF Receptor Antagonist," Biochemical and Biophysical Research Communications, 150(3):1213-1220 (1988).
Sahoo, et al., "Synthesis and Biological Activity of MK 287 (L-680,573): A Potent, Specific, and Orally Active PAF Receptor Antagonist," Bioorg. & Med Chem. Lett., 1(6):327-332 (1991).
Schwenk, et al., "Identification of 5-Oxo-15-hydroxy-6,8,11,13-eicosatetraenoic Acid as a Novel and Potent human Eosinophil Chemotactic Eicosanoid " J. Biol. Chem. 267(18):12482-12488 (1992).
Seminaro and Gleich, "The role of eosinophils in the pathogenesis of asthma," Curr. Opin. in Immunol., 6:860-864 (1994).
Shen, T.Y., "Characterization of a Platelet-A
Biftu Tesfaye
Cai Xiong
Fura Aberra
Grewal Gurmit
Hussoin Sajjat
CytoMed, Inc.
Knowles Sherry M.
Lambkin Deborah
Raymond Richard L.
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-1027377