Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1992-10-21
1994-11-01
Naff, David M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 289, 514934, A61K 3170, C07H 1923
Patent
active
053607953
ABSTRACT:
This invention relates to novel polysubstituted benzimidazoles and compositions and their use in the treatment of viral infections. The polysubstituted benzimidazoles and compositions of the present invention exhibit antiviral properties against viruses of the herpes family, particularly human cytomegalovirus (HCMV) and herpes simplex viruses (HSV). Preferred polysubstituted benzimidazoles of the invention are 2,5,6-Trichloro-1-(.beta.-D-5-deoxyribofuranosyl)benzimidazole and 2-bromo-5,6-dichloro-1-(5-deoxy-.beta.-D-ribofuranosyl)benzimidazole.
REFERENCES:
patent: 3037980 (1962-06-01), Hitchings et al.
patent: 3311628 (1967-03-01), Partyka
patent: 3631036 (1971-12-01), Kim et al.
patent: 3817982 (1974-06-01), Verheyden et al.
patent: 3867386 (1975-02-01), Kim et al.
patent: 3962211 (1976-06-01), Townsend et al.
patent: 4199574 (1980-04-01), Schaeffer
patent: 4229453 (1980-10-01), Roth et al.
patent: 4596798 (1986-01-01), Shipman, Jr. et al.
patent: 4777129 (1988-10-01), Dattagupta et al.
patent: 4892865 (1990-01-01), Townsend et al.
patent: 4927830 (1990-05-01), Townsend et al.
patent: 4968686 (1990-11-01), Townsend et al.
patent: 5248672 (1993-09-01), Townsend et al.
Zou, R., "Synthesis and Antiviral Activity of 1-.beta.-D-Ribofuranosyl-2,4,6-Tri-Chlorobenzimidazole," American Chemical Society, Apr. 1990 describes compound 81 in the application.
Devivar, R. V. et al., "The Formation of an Unusual Product During Studies on the Diazotization of Certain 2-Aminobenzimidazoles," American Chemical Society, Apr. 1990.
Saluja, S. et al., "Synthesis and Antiviral Activity of Certain 2-Substituted 4,5,6,7-Tetrachlorobenzimidazole Acyclic Nucleosides," American Chemical Society, Apr. 1990.
Ramasamy, K. et al., "Total Synthesis of 22/3-Deoxytoyocamycin, 22/3-Deoxysangivamycin and Related 7-.beta.-D-Arabinofuranosyl-Pyrrolo[2,3-d]Pyrimidines via Ring Closure of Pyrrole Precursors Prepared by the Steropspecific Sodium Salt Glycosylation Procedure", Nucleic Acid Research Institute, (Abstract 65).
Nassiri et al., "Kinetic Assessment by Flow Cytometry of the Effect of Two New Antiviral Drugs on the Cell Cycle", 3rd Annual Meeting Clinical Applications of Cytometry, Sep. 1988.
Drach et al., "Comparison of Activity of Tubercidin Analogs Against Herpesviruses", 28th ICAAC, Los Angeles, Calif., Oct. 1988.
Tamm, I., "Inhibitor of Influenza and Mumps Virus Multiplication by 4,5,6,-(or 5,6,7,-) Trichloro-1-.beta.-D-Ribofuranosyl-benzimidazole," Science, 120:847-848 (1954) discloses DRB and TRB.
Smith, C. M. et al., "Inhibitors of Hypoxanthine Metabolism in Ehrlich Ascites Tumor Cells in Vitro," Cancer Treat Rep., 60:1567-1584 (1976) depicts the structure of compound 45 of the application (p. 1575, NSC No. 145391).
Townsend, L. B. et al., "Benzimidazole Nucleosides, Nucleotides, and Related Derivatives," Chemical Reviews, 70:389-438 (1970) depicts the structure of compound 45 of the application (p. 431 Ref. 174).
Bergstom, D. et al., "Antiviral Activity of C-5 Substituted Tubercidin Analogues", J. Med Chem., 27:285-292 (1984).
Turk, S. R. et al., "Pyrrolo[2,3-d]Pyrimidine Nucelosides as Inhibitors of Human Cytomegalovirus", Antimicrob. Agents Chemother., 31:544-550 (1987).
DeClercq, E. et al., "Antirhinovirus Activity of Purine Nucleoside Analogs", Antimicrob. Agents Chemother., 29:482-487 (1986).
Pudlo, J. S. et al., "Synthesis and Antiviral Activity of Certain 4- and 4,5-Disubstituted 7-[2-Hydroxyethoxy)methyl]pyrrolo[2,d-d]pyrimidines", J. Med. Chem., 31:2086-2092 (1988).
Shipman, C., Jr., "Antiviral Activity of Arabinosyladenine and Arabinosylhypoxanthine in Herpes Simplex Virus-Infected KB Cells: Selective Inhibition of Viral Deoxyribonucleic Acid Synthesis in Synchronized Suspension Cultures", Antimicrob. Agents Chemother., 9:120-127 (1976).
Mitsuya, H. et al., "3'-Azido-3'deoxythymidine (BWA 5090): An Antiviral Agent That Inhibits the Infectivity and Cytopathic Effect of Human T-Lymphotropic Virus Type III/Lymphadenopathy-Associated Virus in vitro", PNAS (U.S.A.), 82:7096-7100 (1985).
Mitsuya, H. et al., "Inhibition of the in vitro Infectivity and Cytophatic Effect of Human T-Lymphotrophic Virus Type III/Lymphadenopathy-Associated Virus (HTLVL-III/LAV) by 2',3'-Dideoxynucleosides", PNAS (U.S.A.) 83:1911-1915 (1986).
Robins, M. J. et al., "Nucleic Acid Related Compounds.24.Transformation of Tubercidin 22/3,32/3-O-Orthoacetape into Halo, Deoxy, Epoxide, and Unsaturated Sugar Nucleosides.sup.1,2 ", 55:1251-1259 (1977).
Gupta, P. K. et al., "Synthesis, Cytotoxicity, and Antiviral Activity of Some Acyclic Analogues of Pyrrolo[2,3-d]Pyrimidine Nucleoside Antibiotics Tubercidin, Toyocamycin, and Sangivamycin", J. Med. Chem., 32:402-408, (1989).
Saxena, N. K. et al., "Synthesis and Antiviral Activity of Certain 4-Substituted and 2,4-Disubstituted 7-[(-2-Hydroxyethoxy)methyl]Pyrrolo[2,3-d]Pyrimidines", J. Med. Chem., 31:1501-1506 (1988).
Maruyama, T. et al., "Pyrrolopyrimidine Nucleosides. 18. Synthesis and Chemotherapeutic Activity of 4-Amino-7-(3-deoxy-.beta.-D-Ribofuransoyl)Pyrrolo[2-,3-d]Pyrimidine-5-Carb oxamide (22/3-Deoxysangivamycin)", J. Med. Chem., 26:25-29 (1983).
Drach, J. C. et al., "Tritiated Thymidine Incorporation Does Not Measure DNA Synthesis in Ribavirin-Treated human Cells", Science, 212:549-511 (1981).
DeClercq, E. et al., "Nucleic Acid Related Compounds 51. Synthesis and Biological Properties of Sugar-Modified Analogues of the Nucleoside Antibiotics Tubercidin, Toyocamycin, Sangivamycin, and Formycin", J. Med. Chem., 30:481-486 (1987).
Robins, M. J. et al., "A Mild Conversion of Vicinal Doils to Alkenes, Efficient Transformation of Ribonucleosides into 22/3-ene and 22/3,32/3-Dideoxynucleosides", Tetrahedron Letters, 25:367-370 (1984).
Jain, T. C. et al., "Reactions of 2-Acyloxyisobutyryl Halides with Nucleosides. III. Reactions of Tubercidin and Formycin", J. Org. Chem., 38:3179-3186 (1973).
Tolman, R. L. et al., "Pyrrolopyrimidine Nucleosides. III. The total Synthesis of Toyacamycin, Sangivamycin, Tubercidin, and Related Derivatives", J. Am. Chem. Soc. 91:2102-2108 (1969).
Duffy, T. et al., "Pyrrolo[2,3-d]Pyrimidines, Synthesis from 4-Pyrimidyhydrazones, a 2-Bis(methylthio)methyleneaminopyrrolo-3-carbonitrile, and a Pyrrolo[2-,3-d][1,3]Thiazine-2(1H)-Thione", J. Chem. Soc., Perkin Trans I 16:1921-1929 (1974).
Vindelov, L. L., "Flow Mirofluorometric Analysis of Nuclear DNA in Cells from Solid Tumors and Cells Suspensions", Virchow's Arch. Cell Pathol. 24:227-242 (1977).
Gladler, H., "Nucleic Acid Hybridization for Measurement of Effects of Antiviral Compounds on Human Cytmegalovirus DNA Replication", Antimicrob. Agents Chemother., 24:370-374 (1983).
Shipman, C., Jr. et al., "Evaluation of 4-(2-Hydroxyethyl)-1-piperazineethanesulfonic Acid (HEPES) as a Tissue Culture Buffer", Proc. Soc. Exp. Biol. Med. 120:305-310 (1969).
Hayflick, B. "Screening Tissue Cultures for Mycoplasma Infections," in P. F. Kruse, Jr. and M. K. Patterson, Jr. (ed), Tissue culture:methods and applications. Academic Press Inc., New York, 1973, pp. 722-728.
Sigma Chemical Co. Catalog, St. Louis, Mo., 1984, p. 898 lists tubercidin.
Hansske, F. et al., "22/3 and 32/3-Ketonucleosides and Their Arabino and Xylo Reduction Products", Tetrahedron 40:125-135 (1984).
Drach John C.
Townsend Leroy B.
Meller Michael V.
Naff David M.
The Regents of the University of Michigan
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