Studies designed to increase the stability and antiviral activity (HCMV) of the active benzimidazole nucleoside, TCRB

Nucleosides and Nucleotides

Volumn 18, Issue 4-5, 1999, Pages 509-519

  Townsend, Leroy B ^a   Gudmundsson, Kristjan S ^a   Daluge, Susan M ^b   Chen, Jiong J ^a   Zhu, Zhijian ^a   Koszalka, George W ^b   Boyd, Leslie ^b   Chamberlain, Stanley D ^b   Freeman, George A ^b   Biron, Karen K ^b   Drach, John C ^a  

^a UNIVERSITY OF MICHIGAN SCHOOL OF DENTISTRY   (United States)

^b GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,5,6 TRICHLORO 1 (BETA DEXTRO RIBOFURANOSYL)BENZIMIDAZOLE; BENZIMIDAZOLE DERIVATIVE; CIDOFOVIR; FOSCARNET; GANCICLOVIR; UNCLASSIFIED DRUG; VIRUS DNA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTIVIRAL ACTIVITY; CONFERENCE PAPER; DRUG MECHANISM; DRUG POTENCY; DRUG STABILITY; DRUG STRUCTURE; HUMAN CYTOMEGALOVIRUS; MINIMUM INHIBITORY CONCENTRATION; MONKEY; NONHUMAN; RAT; VIRUS INHIBITION;

ANIMALIA; DNA VIRUSES; HUMAN HERPESVIRUS 5;

EID: 0032989644     PISSN: 07328311     EISSN: None     Source Type: Journal    
DOI: 10.1080/15257779908041486     Document Type: Conference Paper

References (38)

1. (a) Krech, U.; Jung, M.; Jung, F. Cytomegalovirus Infections of Man; S. Karger publishers: New York, 1971; pp 19-32.
2. (b) Alford, C. A.; Britt, W. J. Cytomegalovirus. The Human Cytomegalovirus, Roizman, B.; Whitley, R. J.; Lopez, C., Eds.; Raven Press: New York, 1993; 227-255.
3. Wingard, J. R.; Piantadosi, S.; Burns, W. H.; Zahurak, M. L.; Santos, G. W.; Saral, R. Cytomegalovirus Infections in Bone Marrow Transplant Recipients Given Intensive Cytoreductive Therapy, Rev. Infect. Dis. 1990, 12, S793-S804.
4. (a) McKenzie, R.; Travis, W. D.; Dolan, S. A.; Pittaluga, S.; Feuerstein, I. M.; Shelhamer, J.; Yarchoan, R.; Masur, H. The Cause of Death in Patients with Human Immunodeficiency Virus Infection: A Clinical and Pathological Study with Emphasis on the Role of Pulmonary Diseases. Medicine 1991, 70, 326-343.
5. (b) Vinters, H. V.; Kwok, M. K.; Ho, H.W. Cytomegalovirus in the Nervous System of Patients with the Acquired Immune Deficiency Syndrome. Brain 1989, 112, 245-268.
6. Britt, W. J.; Pass, R. F.; Stagno, S.; Alford, C. A. Pediatric Cytomegalovirus Infection. Transplant. Proc. 1991, 23, 115-117.
7. Faulds, D., Heel, R. C. Ganciclovir: A Review of its Antiviral Activity, Pharmacokinetic Properties and Therapeutic Efficacy in Cytomegalovirus Infections. Drugs 1990, 39, 597-638.
8. Chrisp, P.; Clissold, S. P. Foscarnet. A Review of its Antiviral Activity, Pharmacokinetic Properties and Therapeutic use in Immunocompromised Patients with Cytomegalovirus Retinitis. Drugs, 1991, 41, 104-129.
9. (a) Bronson, J. J.; Ghazzouli, I.; Hitchcock, M. J. M.; Webb, R. R.; Martin, J. C. Synthesis and Antiviral Activity of the Nucleotide Analogue (S)-1-[3-Hydroxy-2-(phosphonylmethoxy)-propyl]cytosine. J. Med. Chem. 1989, 32, 1457-1463.
10. (b) Lalezari, J. P.; Drew, W. L.; Glutzer, E.; James, C.; Miner, D.; Flaherty, J.; Fisher, P. E.; Cundy, K.; Hannigan, J.; Martin, J. C.; Jaffe, H. S. (S)-1-[3-Hydroxy-2-(phosphonylmethoxy) propyl]cytosine (Cidofovir): Results of a Phase I/II Study of a Novel Antiviral Nucleotide Analogue. J. Infect. Dis. 1995, 171, 788-796.
11. Field, A. K.; Biron, K. K. The End of Innocence Revisited: Resistance to Antiviral Drugs. Clin. Micro. Rev. 1994, 7, 1-13.
12. (a) Townsend, L. B., Revankar, G. R., Benzimidazole Nucleosides, Nucleotides, and Related Derivatives. Chem. Rev. 1970, 70, 389-438.
13. (b) Revankar, G. R., Townsend, L. B. The Synthesis of 2-Chloro-1-(β-D-ribofuranosyl)benzimidazole and Certain Related Derivatives. J. Heterocycl. Chem. 1968, 5, 477-483.
14. (a) Devivar, R. V.; Drach J. C.; Townsend, L. B. Benzimidazole Ribonucleosides: Observation of an Unexpected Nitration when Performing Nonaqueous Diazotizations with t-Butyl Nitrate. Bioorg. & Med. Chem. Lett. 1992, 2, 1105-1110.
15. (b) Devivar, R. V.; Kawashima, E.; Revankar, G. R.; Breitenbach, J. M.; Kreske, E. D.; Drach, J. C.; Townsend, L. B. Benzimidazole Ribonucleosides: Design, Synthesis and Antiviral Activity of Certain 2-(Alkylthio)-and 2-(Benzylthio)-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazoles. J. Med. Chem. 1994, 37, 2942-2949.
16. Townsend, L. B.; Devivar, R. V.; Turk, S. R.; Nassiri, M. R.; Drach, J. C. Design, Synthesis and Antiviral Activity of Certain 2,5,6-Trihalo-1-(β-D-ribofuranosyl)benzimidazoles. J. Med. Chem. 1995, 38, 4098-4105.
17. (a) Turk, S. R.; Black, J. M.; Borysko, K. Z.; Edwards, C. A.; Nassiri, M. R.; Townsend, L. B.; Drach, J. C. Benzimidazole Ribonucleosides: Mode of Action of TCRB in HCMV-Infected Cells. Fifth International Conference on Antiviral Research, Vancouver, British Columbia, Canada, March 1992.
18. (b) Drach, J. C.; Townsend, L. B.; Nassiri, M. R.; Turk, S. R.; Coleman, L. A.; Devivar, R. V.; Genzlinger, G; Kreske, E. D.; Renau, T. E.; Westerman, A. C.; Shipman, C. Jr.; Biron, K. K.; Dornsife, R. and Kern, E. R. Benzimidazole Ribonucleosides: A New Class of Antivirals with Potent and Selective Activity Against Human Cytomegalovirus. Fifth International Conference on Antiviral Research, Vancouver, British Columbia, Canada, March 1992.
19. (a) Underwood, M. R.; Biron, K. K.; Hemphill, M. L.; Miller, T. J.; Stanat, S. C.; Drach, J. C.; Townsend L. B.; Harvey, R. J. The Benzimidazole Riboside, 2-Bromo-5,6-dichloro-1-β-D-ribofuranosyl Benzimidazole (BDCRB), Prevents Maturation of Concatemeric Viral DNA in HCMV-Infected Cells, 4th International CMV Conference, Institut Pasteur, Paris, France, April 1993.
20. (b) Underwood, M. R.; Biron, K. K.; Hemphill, M. L.; Stanat, S. C.; Dornsife, R. E.; Drach, J. C.; Townsend L. B.; Edwards, C. A.; Harvey, R. J. High Molecular Weight HCMV DNA does not Properly Mature in Presence of 2-Bromo-5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (BDCRB), Herpesvirus Workshop, Pittsburgh, PA, July 1993.
21. (c) Underwood, M. R.; Stanat, S. C.; Drach, J. C.; Harvey, R. J.; Biron, K. K. Inhibition of HCMV DNA Processing by a new class of Anti-HCMV Compounds is Mediated through the UL89 Gene Product, Herpesvirus Workshop, Vancouver, B.C., August 1994.
22. (d) Underwood, M. R.; Stanat, S. C.; Townsend, L. B.; Drach, J. C.; Biron, K. K. Inhibition of HCMV DNA Processing by a New Class of Anti-HCMV Compounds (Benzimidazole Ribosides) is Mediated through the UL89 Gene Product, 8th International Conference on Antiviral Research, Santa Fe, NM, April 1995.
23. Good, S. S.; Owens, B. S.; Townsend, L. B.; Drach, J. C. 7th International Conference on Antiviral Research, abstract 128, Charleston, S.C. March 1994.
24. Townsend, L.B.; Drach, J.C.; Good, S.S.; Daluge, S.M.; Martin, M.T. Therapeutic Nucleosides. Patent applied for 9 March 1992, Issued 9 July 1996 as U.S. Patent 5,534,535.
25. Townsend, L.B.; Drach, J.C.; Good, S.S.; Daluge, S.M.; Martin, M.T. Antiviral Nucleoside Analogs Containing A Substituted Benzimidazole Base Attached to a Carbocyclic Ring. Patent applied for 8 March 1993.
26. Koszalka, G.W.; Chamberlain, S.D.; Harvey, R.J.; Frick, L.W.; Good, S.S.; Davis, M.L.; Smith, A.; Drach, J.C.; Townsend, L.B.; Biron, K.K. Benzimidazoles for the Treatment of Human Cytomegalovirus Infection. Antiviral Res. 1996, 30, A43.
27. Thiem, J.; Rash, D. Synthesis and Perkow Reaction of Uridine Derivatives. Nucleosides and Nucleotides 1985, 4, 487.
28. Herdewijn, P.; Aerchot, A.; Kerremans, L. Synthesis of Nucleosides Fluorinated in the Sugar Moiety. The Application of Diethylaminosulfur Trifluoride to the Synthesis of Fluorinated Nucleosides. Nucleosides and Nucleotides 1989, 8, 65-96 and references therein.
29. Howell, H. G.; Brodfuehrer, P. R.; Brundige, S. P.; Benigne, D. A.; Sapino, C. Antiviral Nucleosides. A Stereospecific, Total Synthesis of 2′-Fluoro-2′-deoxy-β-D-arabinofuranosyl Nucleosides. J. Org. Chem. 1988, 53, 85-88.
30. Montgomery, J. A.; Shortnacy, A. T.; Carson, D. A.; Secrist III, J. A. 9-(2-Deoxy-2-fluoro-β-D-arabinofuranosyl)guanine: A Metabolically Stable Cytotoxic Analogue of 2′-Deoxyguanosine. J. Med. Chem. 1986, 29, 2389-2392.
31. Codington, J. F.; Doerr, I. L.; and Fox, J. J. Nucleosides. XVIII. Synthesis of 2′-Fluorothymidine, 2′-Fluorodeoxyuridine, and Other 2′-Halogeno-2′-Deoxy Nucleosides. J. Org. Chem, 1964, 29, 558-564.
32. Gudmundsson, K.S.; Freeman, G.A.; Drach, J.C.; Townsend, L.B. Synthesis of Fluorosugar Analogs of 2,5,6-Trichloro-1-(β-D-ribofuranosyl)benzimidazole as Antivirals with Potentially Increased Glycosidic bond Stability, J. Med. Chem., Submitted.
33. (a) Kazunari, O.; Yasuo, I.; Harutoshi, Y. European Patent 0 383 319 A2, 1990.
34. (b) Ishida, Y.; Ohta, K.; Nakahama, T.; Yoshikawa. H. European Patent 0 238 070 A2, 1987.
35. Hayashi, H.; Nakanishi, K.; Brandon, C.; Marmur, J. Structure and Synthesis of Dihydroxypentyluracil from Bacteriophage SP-15 Deoxyribionucleic Acid, J. Am. Chem. Soc. 1973, 8749-8757.
36. Gudmundsson, K.S.; Drach, J.C.; Townsend, L.B. Synthesis of the First C3 Ribosylated Imidazo[1,2-a]pyridine C-Nucleoside by Enantioselective Construction of the Ribose Moiety, J. Org. Chem., 1998, 63, 984-989.
37. Levy, L.; Synth. Commun., 1983, 13, 639-648.
38. Zhu, Z.; Drach, J.C.; Townsend, L.B.; Synthesis of 2,6,7-Trichloro-1-(β -D-ribofuranosyl)naphtho[2,3-d]imidazole: A Linear Dimensional Analogue of the Antiviral Agent TCRB, J. Org. Chem., 1998, 63, 977-983.