Potent and selective inhibition of varicella-zoster virus (VZV) by nucleoside analogues with an unusual bicyclic base

Journal of Medicinal Chemistry

Volumn 42, Issue 22, 1999, Pages 4479-4484

  McGuigan, Christopher ^a   Yarnold, Christopher J ^a   Jones, Garry ^a   Velázquez, Sonsoles ^a   Barucki, Hubert ^a   Brancale, Andrea ^a   Andrei, Graciela ^b   Snoeck, Robert ^b   De Clercq, Erik ^b   Balzarini, Jan ^b  

^a CARDIFF UNIVERSITY   (United Kingdom)

^b REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

3 (2' DEOXY BETA DEXTRO RIBOFURANOSYL) 6 DECYL 2,3 DIHYDROFURO(2,3 D)PYRIMIDIN 2 ONE; 3 (2' DEOXY BETA DEXTRO RIBOFURANOSYL) 6 DODECYL 2,3 DIHYDROFURO(2,3 D)PYRIMIDIN 2 ONE; 3 (2' DEOXY BETA DEXTRO RIBOFURANOSYL) 6 HEPTYL 2,3 DIHYDROFURO(2,3 D)PYRIMIDIN 2 ONE; 3 (2' DEOXY BETA DEXTRO RIBOFURANOSYL) 6 HEXYL 2,3 DIHYDROFURO(2,3 D)PYRIMIDIN 2 ONE; 3 (2' DEOXY BETA DEXTRO RIBOFURANOSYL) 6 NONYL 2,3 DIHYDROFURO(2,3 D)PYRIMIDIN 2 ONE; 3 (2' DEOXY BETA DEXTRO RIBOFURANOSYL) 6 OCTYL 2,3 DIHYDROFURO(2,3 D)PYRIMIDIN 2 ONE; 3 (2' DEOXY BETA DEXTRO RIBOFURANOSYL) 6 PENTYL 2,3 DIHYDROFURO(2,3 D)PYRIMIDIN 2 ONE; 3 (2' DEOXY BETA DEXTRO RIBOFURANOSYL) 6 UNDECYL 2,3 DIHYDROFURO(2,3 D)PYRIMIDIN 2 ONE; ACICLOVIR; ANTIVIRUS AGENT; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; CYTOTOXICITY; DRUG POTENCY; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION; VARICELLA ZOSTER VIRUS; VIRUS INHIBITION;

EID: 0033524026     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990346o     Document Type: Article

References (24)

1. De Clercq, E. Antiviral and Antitumor Activities of 5-Substituted 2′-Deoxyuridines, Methods Find. Exp. Clin. Pharmacol. 1980, 2, 253-267.
2. De Clercq, E. Biochemical aspects of the selective antiherpes activity of Nucleoside Analogues. Biochem. Pharmacol. 1984, 33 (14), 2159-2169.
3. De Clercq, E.; Descamps, J.; DeSomer, P.; Barr, P. J.; Jones, A. S.; Walker, R. T. (E)-5-(2-Bromovinyl)-2′-Deoxyuridine, A Potent and Selective Antiherpes Agent. Proc. Natl. Acad. Sci. U.S.A. 1979, 76, 2947-2951.
4. De Clercq, E.; Descamps, J.; Verhelst, G.; Walker, R. T.; Jones, A. S.; Torrence, P. F.; Shugar, D. Comparative Efficacy of Antiherpes Drugs Against Different Strains of Herpes Simplex Virus. J. Infect. Dis. 1980, 141, 563-574.
5. De Clercq, E.; Balzarini, J.; Torrence, P. F.; Mertes, M. P.; Schmidt, C. L.; Shugar, D.; Barr, P. J.; Jones, A. S.; Verhelst, G.; Walker, R. T. Thymidylate Synthetase as target enzyme for the inhibitory activity of 5-substituted 2′-deoxyuridines on mouse leukemia - L1210 cell. Mol. Pharmacol. 1981, 19, 321-330.
6. Cheng, Y. C.; Dutschman, G.; De Clercq, E.; Jones, A. S.; Rahim, S. G.; Verhelst, G.; Walker, R. T. Differential affinities of 5-(2-Halogeno vinyl)-2′-deoxyuridines for deoxythymidine kinases of various origins. Mol. Pharmacol. 1981, 20 (1), 230-233.
7. Barr, P. J.; Nolan, P. A.; Santi, D. V.; Robins, M. J. Inhibition of thymidylate synthetase by 5-alkynyl-2′-Deoxyuridylates. J. Med Chem. 1981, 24, 1385-1388.
8. McGuigan, C.; Velázquez, S.; De Clercq, E.; Balzarini, J. Synthesis and evaluation of 5-halo 2′,3′-didehydro-2′,3′-dideoxy nucleosides and their blocked phosphoramidates as potential anti-HIV agents: An example of kinase bypass. Antiviral Chem. Chemother. 1997, 8, 519-527.
9. McGuigan, C.; Camarasa, M.-J.; Egberink, H.; Hartmann, K.; Karlsson, A.; Perno, C.-F.; Balzarini, J. Design, Synthesis and Biological Evaluation of Novel Nucleotide Prodrugs as Inhibitors of HIV Replication. Int. Antiviral News 1997, 5, 19-21
10. Balzarini, J.; Kruining, J.; Wedgwood, O.; Pannecouque, C.; Aquaro, S.; Perno, C. F.; Naesens, L.; Witvrouw, M.; Heijtink, R.; De Clercq E.; McGuigan, C. Conversion of 2′,3′-Dideoxyadenosine (ddA) and 2′,3′-Didehydro-2′,3′-Dideoxyadenoaine (d4A) to their corresponding aryloxyphosphoramidate derivatives markedly potentiates their activity against human immunodeficiency virus and hepatitis B virus. FEBS Lett. 1997, 410, 324-328.
11. Robins, M. J.; Barr, P. J. Nucleic-Acid Related-Compounds. 39. Efficient Conversion of 5-Iodo to 5-Alkynyl and derived 5-Substituted Uracil Bases and Nucleosides. J. Org. Chem. 1983, 48, 1854-1862.
12. Robins, M. J.; Barr, P. J. Nucleic-Acid Related-Compounds. 31. Smooth and Efficient Palladium Copper Catalyzed Coupling of Terminal Alkynes with 5-Iodouracil Nucleosides. Tetrahedron Lett. 1981, 22, 421-424.
13. Crisp, G. T.; Flynn, B. L. Palladium-Catalyzed Coupling of Terminal Alkynes with 5-(Trifluoromethanesulfonyloxy)Pyrimidine Nucleosides. J. Org. Chem. 1993, 58, 6614-6619.
14. Robins, M. J.; Vinayak, R. S.; Wood, S. G. Nucleic-Acid Related-Compounds. 59. Solvent, not Palladium Oxidation-State, is the Primary Determinant for Successful Coupling of Terminal Alkynes with Iodo Nucleosides. Tetrahedron Lett. 1990, 31, 3731-3734.
15. Bleackley, R. C.; Jones, A. S.; Walker, R. T. Incorporation of 5-substituted uracil derivatives into nucleic acids - III Synthesis of 5-substituted uracils derived from 5 acetyluracil. Tetrahedron 1978, 32, 2795-2797.
16. Kumar, R.; Knaus, E. E.; Wiebe, L. I. Synthesis and Biological Evaluation of 5-(1-Alkoxy-2-Haloethyl)-2′-Deoxyuridines and Related Uracil Analogues. J. Heterocycl. Chem. 1991, 28, 1917-1925.
17. Eger, K.; Jalalian, M.; Schmidt, M. J. Steric Fixation of Bromovinyluracil - Synthesis of Furo [2,3-D]Pyrimidine Nucleosides. Heterocycl. Chem. 1995, 32, (18) Kumar, R.; Wiebe, L. I.; Knaus, E. E. Synthesis of 5-(1-azidovinyl) and [2-(1-azirinyl)] analogues of 2′-deoxyuridine. Can. J. Chem. 1990, 74, 1609-1615.
18. Eger, K.; Jalalian, M.; Schmidt, M. J. Steric Fixation of Bromovinyluracil - Synthesis of Furo [2,3-D]Pyrimidine Nucleosides. Heterocycl. Chem. 1995, 32, (18) Kumar, R.; Wiebe, L. I.; Knaus, E. E. Synthesis of 5-(1-azidovinyl) and [2-(1-azirinyl)] analogues of 2′-deoxyuridine. Can. J. Chem. 1990, 74, 1609-1615.
19. Inoue, H.; Imura, A.; Ohtsuka, E. Synthesis of Dodecadeoxyribonucleotides Containing a Pyrrolo[2,3-D]Pyrimidine Nucleoside and their base-pairing Ability. Nippon Kagaku Kaishi 1987, 7, 1214-1220
20. Tolstikov, G. A.; Mustmafin, A. G.; Gataullin, R. R.; Spirikhin, L. V.; Sultanova, V. S.; Abdrakhanov, I. B. Oxidative Addition of Unsaturated Acid-Esters to 1,3-Dimethyluracil and Pyrimidine Nucleosides. I Nauk. Ser. Khim. 1993, 596-598.
21. De Clercq, E.; Holy, A.; Rosenberg, I.; Sakuma, T.; Balzarini, J.; Maudgal, P. C. A Novel Selective Broad-Spectrum Anti-DNA virus Agent. Nature 1986, 324, 464-467.
22. Values calculated using ClogP 1.0, Biobyte Corporation, Claremont, CA.
23. Peck, W.; Crome, P.; Wood, M. J.; McKendrick, M. W.; Bannister, B.; Mandal, B. K.; Crooks, R. J. Multiple dose netivudine, a potent anti-varicella zoster virus agent, in healthy elderly volunteers and patients with shingles. J. Antimicrobial Chemother. 1996, 37, 583-597.
24. Rahim, S. G.; Trevidi, N.; Selway, J.; Darby, G.; Collins, P.; Powell, K. L.; Purifoy, D. M. J. 5-Alkynyl pyrimidine nucleosides as potent selective inhibitors of varicella-zoster virus. Antiviral Chem. Chemother. 1992, 3, 293-297.