Purine Nucleoside Analogs as Antiviral Agents

  • John C. Drach
Part of the NATO ASI Series book series (NSSA, volume 73)


In a book and conference dealing with “targets” for antiviral agents, a discussion on the “magic bullets”* used to treat virus diseases might seem out of place. The study of existing drugs and active compounds is, however, most appropriate in the context of designing new and better antivirals. As Prusoff2 has pointed out, the knowledge of a specific chemotherapeutic target has not yet led to the synthesis of a specific drug. Until highly detailed physical-chemical data on sites of inhibition and modes of drug-receptor interaction are obtained and interpreted, this approach will remain a longer term goal. A more achievable goal is the application of mode of action data on existing agents to the design of new and better drugs. In addition, both new and existing drugs can be used to probe known targets and to search for new ones.


Herpes Simplex Virus Antiviral Activity Antiviral Agent Adenosine Deaminase Uninfected Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    P. Ehrlich, Berichte 42: 17 (1909).Google Scholar
  2. 2.
    W.H. Prusoff and P.H. Fisher, in: “Nucleoside Analogs: Chemistry, Biology and Medical Applications,” R.T. Walker, E. DeClercq and F. Eckstein, eds., Plenum Press, New York (1979) p. 281.Google Scholar
  3. 3.
    D.L. Swallow, Prog. Drug Res. 22: 268 (1978).Google Scholar
  4. 4.
    R.W. Sidwell and J.T. Witkowski, in: “Burger’s Medicinal Chemistry, 4th ed., Part II,” M. E. Wolff, ed., John Wiley and Sons, New York, (1979) p. 543.Google Scholar
  5. 5.
    G.J. Galasso, T.C. Merigan and R.A. Buchanan, eds., “Antiviral Agents and Viral Diseases of Man,” Raven Press, New York, (1979).Google Scholar
  6. 6.
    R.J. Suhadolnik, “Nucleosides as Biological Probes,” John Wiley and Sons, New York, (1979).Google Scholar
  7. 7.
    E.C. Herman, Jr. and J.A Hermann, Pharmacol. Therap. 7: 35 (1979).CrossRefGoogle Scholar
  8. 8.
    E. DeClercq, Arch. Int. Physiol. Biochim. 87: 353 (1979).CrossRefGoogle Scholar
  9. 9.
    T.W. North and S.S. Cohen, Pharmacol. Ther. 4: 81 (1979).CrossRefPubMedGoogle Scholar
  10. 10.
    J.C. Drach, Ann. Rep. Med. Chem. 15: 149 (1980).Google Scholar
  11. 11.
    W.M. Shannon and F.M. Schabel, Jr., Pharmacol. Ther. 11: 263 (1980).CrossRefPubMedGoogle Scholar
  12. 12.
    M.S. Hirsch and M.N. Swartz, N. Engl. J. Med. 302:903 and 949 (1980).Google Scholar
  13. 13.
    F.E. Hahn, ed., “Virus Chemotherapy,” Vol. 27 of “Antibiotics and Chemotherapy,” S. Karger, Basel (1980).Google Scholar
  14. 14.
    R.A. Smith, R.W. Sidwell and R.K. Robins, Ann. Rev. Pharmacol Toxicol. 20: 259 (1980).CrossRefGoogle Scholar
  15. 15.
    L.H. Collier and J. Oxford, eds., “Developments in Antiviral Therapy,” Academic Press, London (1980).Google Scholar
  16. 16.
    K.K. Guari, ed., “Antiviral Chemotherapy: Design of Inhibitors of Viral Functions,” Academic Press, New York (1981).Google Scholar
  17. 17.
    E. DeClercq, Biochem. J. 205: 1 (1982).Google Scholar
  18. 18.
    T.C. Merigan and H.E. Revis, in: “Nucleoside Analogues; Chemistry Biology and Medical Applications,” R.T. Walker, E. De Clercq and F. Eckstein, eds., Plenum Press, New York, (1979) p. 395.Google Scholar
  19. 19.
    S. Kit, Pharmacol. Ther. 4: 501 (1979).CrossRefGoogle Scholar
  20. 20.
    Y.-C. Cheng, K. Nakayama, D. Derse, K. Bastow, J. Ruth, R.-S. Tan, G. Dutschman, S.J. Cardona and S. Grill, in: “Herpesvirus: Clinical, Pharmacological and Basic Aspects,” H. Shiota, Y.-C. Cheng and W. Prusoff, eds., Excerpta Medica, Amsterdam (1982) P. 47.Google Scholar
  21. 21.
    R. Whitley, C. Alford, F. Hess and R. Buchanan, Drugs 20: 267 (1980).CrossRefPubMedGoogle Scholar
  22. 22.
    D. Pavan-Langston, R.A. Buchanan, C.A. Alford, Jr., eds., “Adenine Arabinsodie: An Antiviral Agent,” Raven Press, New York (1975) p. 197 ff.Google Scholar
  23. 23.
    W.M. Shannon, ibid., p. 1.Google Scholar
  24. 24.
    B.J. Sloan, ibid., p. 45.Google Scholar
  25. 25.
    J.C. Drach and C. Shipman, Ann. N.Y. Acad. Sci. 284: 396 (1977).CrossRefPubMedGoogle Scholar
  26. 26.
    C. Shipman, Jr., S.H. Smith, R.H. Carlson and J.C. Drach, Antimicrob. Agents Chemother. 9: 120 (1976).CrossRefPubMedGoogle Scholar
  27. 27.
    P.M. Schwartz, C. Shipman, Jr. and J.C. Drach, Antimicrob. Agents Chemother. 10: 64 (1976).CrossRefPubMedGoogle Scholar
  28. 28.
    K.M. Rose, T.B. Leonard and T.H. Carter, Molec. Pharmacol. 22: 517 (1982).Google Scholar
  29. 29.
    W.E.G. Muller, in “Antiviral Agents and Viral Diseases of Man,” G.J. Galasso, T.C. Merigan and R.A. Buchanan, eds., Raven Press, New York (1979) p. 77.Google Scholar
  30. 30.
    J.J. Brink and G.A. Le Page, Cancer Res. 24: 312 (1964).PubMedGoogle Scholar
  31. 31.
    W. Plunkett and S.S. Cohen, Cancer Res. 35: 415 (1975).Google Scholar
  32. 32.
    L.M. Rose and R.W. Brockman, J. Chromatog. 133: 335 (1977).CrossRefGoogle Scholar
  33. 33.
    W.E.G. Müller, R.K. Zahn, J. Arendes, A. Maidhof and H. Umezawa, Z. Physiol. Chem. 359: 1287 (1978).CrossRefGoogle Scholar
  34. 34.
    D.E. Bell and A. Fridland, Biochim. Biophys. Acta 606: 57 (1980).CrossRefPubMedGoogle Scholar
  35. 35.
    T. Chang and A.J. Glazko, Res. Commun. Chem. Path. Pharmacol. 14: 127 (1976).Google Scholar
  36. 36.
    P.M. Schwartz, J.N. Sandberg, C. Shipman, Jr. and J.C. Drach, 15th Interscience Conf. Antimicrob. Agents Chemother., Washington D.C. (1975) Abst. 357.Google Scholar
  37. 37.
    W. Plunkett, S. Chubb, L. Alexander and J.A. Montgomery, Cancer Res. 40: 2349 (1980).PubMedGoogle Scholar
  38. 38.
    D.S. Shewach and W. Plunkett, Cancer Res. 42: 3637 (1982).PubMedGoogle Scholar
  39. 39.
    D.S. Shewach and W. Plunkett, Biochem. Pharmacol. 28: 2401 (1979).CrossRefPubMedGoogle Scholar
  40. 40.
    H.W. Spater, J.A. Schnitzer, N. Quintana, S.H. Spater and A.B. Novikoff, J. Histochem. Cytochem. 29: 693 (1981).CrossRefPubMedGoogle Scholar
  41. 41.
    K.J. Pierre, A.P. Kimball and G.A. LePage, Canad. J. Biochem. 45: 1619 (1967).Google Scholar
  42. 42.
    H.P. Schnebli, D.L. Hill and L.L. Bennett, J. Biol. Chem. 242: 1997 (1967).PubMedGoogle Scholar
  43. 43.
    T.A. Krenitsky, J.V. Tuttle, G.W. Koszalka, I.S. Chen, L.M. Beacham III, J.L. Rideout and G.B. Elion, J. Biol. Chem. 251: 4055 (1976).PubMedGoogle Scholar
  44. 44.
    V. Verhoef, J. Sarup and A. Fridland, Cancer Res. 41: 4478 (1981).PubMedGoogle Scholar
  45. 45.
    C.-H. Chang, R.W. Brockman and L.L. Bennett, Cancer Res. 42: 3033 (1982).PubMedGoogle Scholar
  46. 46.
    W.R. Gower, Jr., M.C. Carr and D.H. Ives, J. Biol. Chem. 254: 2180 (1979).PubMedGoogle Scholar
  47. 47.
    N.B. Katlama and J.C. Drach, unpublished observations.Google Scholar
  48. 48.
    M. Hubert-Habart and S.S. Cohen, Biochim Biophys. Acta 59: 468 (1962).CrossRefPubMedGoogle Scholar
  49. 49.
    S.S. Cohen, Prog. Nucl. Acids Res. Molec. Biol. 5: 1 (1966).Google Scholar
  50. 50.
    R.A. Miller, G.J. Dixon, J. Ehrlich, B.J. Sloan and I.W. McLean, Jr., Antimicrob. Agents Chemother. 1968: 136 (1969).Google Scholar
  51. 51.
    S.H. Smith, C. Shipman, Jr. and J.C. Drach, Cancer Res. 38: 1916 (1978).PubMedGoogle Scholar
  52. 52.
    L.B. Allen, L.K. Vander Slice, C.M. Fingal, F.H. McCright, E.F. Harris and P.D. Cook, Antiviral Res. 2: 203 (1982).CrossRefPubMedGoogle Scholar
  53. 53.
    L.B. Allen, C.J. Hintz, S.M. Wolf, J.H. Huffman, L.N. Simon, R.K. Robins and R.W. Sidwell, J. Infect. Dis. 133: A178 (1976).CrossRefPubMedGoogle Scholar
  54. 54.
    W.E.G. Müller, J. Arendes, A. Maidhof, R.K. Zahn and W. Geurtsen, Chemother. 27: 53 (1981).CrossRefGoogle Scholar
  55. 55.
    D. Derse, K.F. Bastow and Y.C. Cheng, J. Biol. Chem. 257: 10251 (1982).PubMedGoogle Scholar
  56. 56.
    G.A. LePage, Canad. J. Biochem. 48: 75 (1970).Google Scholar
  57. 57.
    S.S. Cohen, Med. Biol. 54: 299 (1976).Google Scholar
  58. 58.
    T. Spector and R.L. Miller, Biochim. Biophys. Acta 445: 509 (1976).CrossRefPubMedGoogle Scholar
  59. 59.
    T. Spector, Biochim. Biophys. Acta 481: 741 (1977).CrossRefPubMedGoogle Scholar
  60. 60.
    N.R. Cozzarelli, Ann. Rev. Biochem. 46: 641 (1977).CrossRefGoogle Scholar
  61. 61.
    W.E.G. Müller, R.K. Zahn and D. Falke, Virology 84: 320 (1978).CrossRefPubMedGoogle Scholar
  62. 62.
    C.M. Reinke, J.C. Drach, C. Shipman, Jr. and A. Weissbach in: “Oncogenesis and Herpesviruses III, Part 2,” G. de The, W. Henle and F. Rapp, eds., IARC Press, Lyon (1978) p. 999.Google Scholar
  63. 63.
    M. Ostrander and Y.-C. Cheng, Biochim. Biophys. Acta 609: 232 (1980).CrossRefPubMedGoogle Scholar
  64. 64.
    A. Okura and S. Yoshida, J. Biochem. 84: 727 (1978).PubMedGoogle Scholar
  65. 65.
    K. Ono, A. Ohashi, A. Yamamoto, A. Matsukago, T. Takahasi, M. Saneyoshi and T. Ueda, Cancer Res. 39: 4673 (1979).PubMedGoogle Scholar
  66. 66.
    H.S. Allaudeen, J.W. Kozavich and A.C. Sortorelli, Nucleic Acids Res. 10: 1379 (1982).CrossRefPubMedGoogle Scholar
  67. 67.
    D.M. Coen, P.A. Furman, P.T. Gelop and P.A. Schaffer, J. Virol. 41: 909 (1982).PubMedGoogle Scholar
  68. 68.
    C.M. Reinke, J.C. Drach, C. Shipman, Jr. and H.S. Allaudeen, submitted to Antiviral Res.Google Scholar
  69. 69.
    J.L. Webb, in: “Enzyme and Metabolic Inhibitors, Vol I, General Principles of Inhibition,” Academic Press, New York (1963) p. 104.Google Scholar
  70. 70.
    W.E.G. Müller, R.K. Zahn, K. Bittlingmaier and D. Falke, Ann. N.Y. Acad. Sci. 284: 34 (1977).CrossRefPubMedGoogle Scholar
  71. 71.
    J.R. Wingard, A.D. Hess, R.K. Stuart, R. Saral and W.H. Burns, Antimicrob. Agents Chemother. 23: 593 (1983).CrossRefPubMedGoogle Scholar
  72. 72.
    J.L. Schardein, D.L. Hentz, J.A. Petrere, J.E. Fitzgerald and S.M. Kurtz, Teratology 15: 231 (1977).CrossRefPubMedGoogle Scholar
  73. 73.
    B. Hafkin, R.B. Pollard, M.L. Tiku, W.S. Robinson and T.C. Merigan, Antimicrob. Agents Chemother. 16: 781 (1979).CrossRefPubMedGoogle Scholar
  74. 74.
    C.-H. Chang and Y.-C. Cheng, Cancer Res. 40: 3555 (1980).PubMedGoogle Scholar
  75. 75.
    B.M. Dutia, J. Gen. Virol. 64: 513 (1983).CrossRefGoogle Scholar
  76. 76.
    E.L. White, S.C. Shaddix, R.W. Brockman and L.L. Bennett, Jr., Cancer Res. 42: 2260 (1982).PubMedGoogle Scholar
  77. 77.
    Y. Langelier and G. Buttin, J. Gen. Virol. 57: 21 (1981).CrossRefPubMedGoogle Scholar
  78. 78.
    W.M. Shannon, R.W. Brockman, G. Arnett and S. Shaddix, 1st Amer. Soc. Virol. Meeting, Ithaca, NY (1982).Google Scholar
  79. 79.
    L.W. Dow, D.E. Bell, L. Poulakos and A. Fridland, Cancer Res. 40: 1405 (1980).PubMedGoogle Scholar
  80. 80.
    D.S. Shewach and W. Plunkett, Biochem. Pharmacol. 31: 2103 (1982).CrossRefPubMedGoogle Scholar
  81. 81.
    T.W. North, Biochem. Pharmacol. in press (1983).Google Scholar
  82. 82.
    G.P veer Reddy and A.B. Pardee, J. Biol. Chem. 257: 12526 (1982).Google Scholar
  83. 83.
    W.E.G. Müller, H.J. Rohde, R. Beyer, A. Maidhof, M. Lachmann, H. Taschner and R.K. Zahn, Cancer Res. 35: 2160 (1975).PubMedGoogle Scholar
  84. 84.
    J.C. Pelling, J.C. Drach and C. Shipman, Jr., Virolo 104: 323 (1981).CrossRefGoogle Scholar
  85. 85.
    D.W. Kufe, P.P. Major, D. Munroe, M. Egan and D. Herrick, Cancer Res. 43: 2000 (1983).PubMedGoogle Scholar
  86. 86.
    W.E.G. Müller, R.K. Zahn, R. Beyer and D. Falke, Virology 76: 787 (1977).CrossRefPubMedGoogle Scholar
  87. 87.
    J.W. Barnett, C.M. Reinke, S.R. Turk and J.C. Drach, submitted to Biochim. Biophys. Acta.Google Scholar
  88. 88.
    D. Derse and Y.-C. Cheng, J. Biol. Chem. 256: 8525 (1981).PubMedGoogle Scholar
  89. 89.
    M.Y.W. Tsang Lee, J.J. Byrnes, K.M. Downey and A.G. So, Biochemistry 19: 215 (1980).CrossRefGoogle Scholar
  90. 90.
    M.S. Hershfield, J. Biol. Chem. 254: 22 (1979).Google Scholar
  91. 91.
    S. Helland and P.M. Ueland, Cancer Res. 42: 1130 (1982).PubMedGoogle Scholar
  92. 92.
    T.O. Eloranta, E.O. Kajander and A.M. Raina, Med. Biol. 60: 272 (1982).PubMedGoogle Scholar
  93. 93.
    G.L. Cantoni and P.K. Chiang, in:“Natural Sulfur Compounds Novel Biochemical and Structural Aspects,” D. Carallini, G.E. Gaull and V. Zappia, eds., Plenum Press, New York (1980) p. 67.Google Scholar
  94. 94.
    N.M. Kredich and M.S. Hershfield, Proc. Natl. Acad. Sci. USA 76: 2450 (1979).CrossRefPubMedGoogle Scholar
  95. 95.
    C.E. Cass, M. Selner, P.J. Ferguson and J.R. Phillips, Cancer Res. 42: 4991 (1982).PubMedGoogle Scholar
  96. 96.
    S.L. Sacks, T.C. Merigan, J. Kaminska and I.H. Fox, J. Clin. Invest. 69: 226 (1982).CrossRefPubMedGoogle Scholar
  97. 97.
    S.L. Sacks, G.H. Scullard, R.B. Pollard, P.B. Gregory, W.S. Robinson and T.C. Merigan, Antimicrob. Agents Chemother. 21: 93 (1982).CrossRefPubMedGoogle Scholar
  98. 98.
    S.M. Kurtz, in: “Adenine Arabinoside: An Antiviral Agent,” D. Pavan-Langstron, R.A. Buchanan and C.A. Alford, Jr., eds., Raven Press, New York (1975) p. 145.Google Scholar
  99. 99.
    N.M. Kredich, J. Biol. Chem. 255: 7380 (1980).Google Scholar
  100. 100.
    D.A. Carson, J. Kaye and J.E. Seegmiller, Adv. Exp. Biol. Med. 122B: 299 (1980).CrossRefGoogle Scholar
  101. 101.
    W.E.G. Müller, R.K. Zahn and J. Arendes, FEBS Lett. 94: 47 (1978).CrossRefPubMedGoogle Scholar
  102. 102.
    G. Hess, W. Arnold and K.-H. Meyer zum Büschenfelde, Antimicrob. Agents Chemother. 19: 44 (1981).CrossRefPubMedGoogle Scholar
  103. 103.
    V.L. Chan and P. Juranka, Somat. Cell Genet. 7: 147 (1981).CrossRefPubMedGoogle Scholar
  104. 104.
    D. Ayusawa, K. Iwata and T. Seno, Cancer Res. 43: 814 (1983).PubMedGoogle Scholar
  105. 105.
    K. Iwata, D. Ayusawa and T. Seno, Gann 73: 167 (1982).PubMedGoogle Scholar
  106. 106.
    G.A. LePage, Cancer Res. 38: 2314 (1978).Google Scholar
  107. 107.
    C.S. Crumpacker, L.E. Schnipper, P.N. Kowalsky and D.M. Sherman, J. Infect. Dis. 146: 167 (1982).CrossRefPubMedGoogle Scholar
  108. 108.
    A.J. Glazko, T. Chang, J.C. Drach, D.R. Mourer, P.E. Borondy, H. Schneider, L. Croskey and E. Maschewske, in: “Adenine Arabinoside: An Antiviral Agent,” D. Pavan-Langston, R.A. Buchanan and C.A. Alford, Jr., eds., Raven Press, New York (1975) p. 111.Google Scholar
  109. 109.
    R.W. Brockman, Y.-C. Cheng, F.M. Schabel and J.A. Montogomery, Cancer Res. 40: 3610 (1980).PubMedGoogle Scholar
  110. 110.
    C.M. Cermak-Mörth, R. Christian and F.M. Unger, Biochem. Pharmacol. 28: 2105 (1979).CrossRefPubMedGoogle Scholar
  111. 111.
    R. Vince and S. Daluge, J. Med. Chem. 20: 612 (1977).CrossRefPubMedGoogle Scholar
  112. 112.
    W.M. Shannon, L. Westbrook, G. Arnett, S. Daluge, H. Lee and R. Vince, Antimicrob. Agents Chemother. in press (1983).Google Scholar
  113. 113.
    C.D. Yu, N.A. Gordon, J.L. Fox, W.I. Higuchi and N.F. Ho, J. Pharm. Sci. 69: 775 (1980).CrossRefPubMedGoogle Scholar
  114. 114.
    R.A. Lipper, S.M. Machkovech, J.C. Drach and W.I. Higuchi, Molec. Pharmacol. 14: 366 (1978).Google Scholar
  115. 115.
    J.T. Richards, E.R. Kern, J.C. Overall, Jr. Antiviral Res. 2: 27 (1982).CrossRefPubMedGoogle Scholar
  116. 116.
    D.C. Baker, T.H. Haskell, S.R. Putt and B.J. Overall, Antiviral Res 22: 273 (1979).Google Scholar
  117. 117.
    W.M. Shannon, G. Arnett, D.C. Baker and W.I. science Conf. Antimicrob. Agents Chemother., 437.Google Scholar
  118. 118.
    O. Sauer, G.T. Werner, H. Schneider, H.G. Lenard, L.V. Haselberg and H.-J. Nettesheim, Klin. Pädiat. 191: 566 (1979).Google Scholar
  119. 119.
    R.J. Whitley, B.C. Tucker, A.W. Kinkel, N.H. Barton, R.F. Pass, J.D. Whelchel, C.G. Cobbs, A.G. Diethelm and R.A. Buchanan, Antimicrob. Agents Chemother. 18: 709 (1980).CrossRefPubMedGoogle Scholar
  120. 120.
    J.H. Hoofnagle, G.Y. Minuk, G.M. Dusheiko, D.F. Schafer, R. Johnson, S. Straus, E.A. Jones, J.L. Gerin and K. Ishak, Hepatol. 2: 784 (1982).CrossRefGoogle Scholar
  121. 121.
    S.L. Spruance, C.J. Crumpacker, H. Haines, C. Bader, K. Mehr, J. MacCalman, L.E. Schnipper, M.R. Klauber, J.C. Overall and the Collaborative Study Group, N. Engl. J. Med. 300: 1180 (1979).CrossRefPubMedGoogle Scholar
  122. 122.
    J.M. Hill, B.S. Kwon, K.D. Burch, J. Deback, I. Whang, G.T. Jones, B. Luke, R. Harp, Y. Shimomura, D.S. Hull and L.P. Gangarosa, Amer. J. Med. 73: 300 (1982).CrossRefPubMedGoogle Scholar
  123. 123.
    G.B. Elion, J.L. Rideout, P. deMiranda, P. Collins and D.J. Bauer, Ann. N.Y. Acad. Sci. 255: 468 (1975).CrossRefPubMedGoogle Scholar
  124. 124.
    G.B. Elion, P.A. Furman, J.A. Fyfe, P. deMiranda, L. Beauchamp and H.J. Schaeffer, Proc. Natl. Acad. Sci. USA 74: 5716 (1977).CrossRefPubMedGoogle Scholar
  125. 125.
    P. Collins and D.J. Bauer, J. Antimicrob. Chemother. 3A: 73 (1977).CrossRefPubMedGoogle Scholar
  126. 126.
    K. Ono, A. Ohashi, A. Yamamoto, A. Matsukage, T. Takahasi, M. Saneyoshi and T. Ueda, Cancer Res. 39: 4673 (1979).PubMedGoogle Scholar
  127. 127.
    H.J. Field, S.E. Bell, G.B. Elion, A.A. Nash and P. Wildy, Antimicrob. Agents Chemother. 15: 554 (1979).CrossRefPubMedGoogle Scholar
  128. 128.
    A. Cohen, J.W.W. Lee and E.W. Gelfand, Blood 61: 660 (1983).PubMedGoogle Scholar
  129. 129.
    H.J. Schaeffer, L. Beauchamp, P. deMiranda, G.B. Elion, D.J. Bauer and P. Collins, Nature 272: 583 (1978).CrossRefPubMedGoogle Scholar
  130. 130.
    L. Corey, A.J. Nahmias, M.E. Guinan, J.K. Benedetti, C.W. Critchlow and K.K. Holmes, New Engl. J. Med. 306: 1313 (1982).CrossRefPubMedGoogle Scholar
  131. 131.
    D.H. King and G. Gallaso, Amer. J. Med. 73: 1 (1982).CrossRefGoogle Scholar
  132. 132.
    S.L. Spruance, L.E. Schnipper, J.C. Overall, Jr., E.R. Kern, B. Wester, J. Modlin, G. Wenerstrom, C. Burton, K.A. Arndt, G.L. Chiu and C.S. Crumpacker, J. Infect. Dis. 146: 85 (1982).CrossRefPubMedGoogle Scholar
  133. 133.
    Y.J. Bryson, M. Dillon, M. Lovett, G. Acuna, S. Taylor, J.D. Cherry, B.L. Johnson, E. Wiesmeier, W. Growdon, T. Creagh-Kirk and R. Keeney, New Engl. J. Med. 308: 916 (1983).CrossRefPubMedGoogle Scholar
  134. 134.
    D.J. Bauer, in:“Developments in Antiviral Therapy,” L.H. Collier and J. Oxford, eds., Academic Press, London (1980) p. 43.Google Scholar
  135. 135.
    D. Brigden, P. Fiddian, A.E. Rosling and T. Ravenscroft, Antiviral Res. 1: 203 (1981).CrossRefPubMedGoogle Scholar
  136. 136.
    S. Alenius, M. Berg, F. Broberg, K. Eklind, B. Lindborg and B. Oberg, J. Infect. Dis. 145: 569 (1982).CrossRefPubMedGoogle Scholar
  137. 137.
    J. Harmenberg, Ph.D. Dissertation, Department of Virology, National Bacteriological Laboratory, Stockholm (1982).Google Scholar
  138. 138.
    C.S. Crumpacker, L.E. Schnipper, J.A. Zaía and M.J. Levin, Antimicrob. Agents Chemother. 15: 642 (1979).CrossRefPubMedGoogle Scholar
  139. 139.
    J.R. Wingard, A.D. Hess, R.K. Stuart, R. Saral and W.H. Burns, Antimicrob. Agents Chemother. 23: 593 (1983).CrossRefPubMedGoogle Scholar
  140. 140.
    L.M. Parker, J.M. Lipton, N. Binder, E.L. Crawford, M. Kudisch and M. Levine, Antimicrob. Agents Chemother. 21: 146 (1982).CrossRefPubMedGoogle Scholar
  141. 141.
    P.A. Furman, M.H. St. Clair, J.A. Fyfe, J.L. Rideout, P.M. Keller and G.B. Elion, J. Virol. 32: 72 (1979).PubMedGoogle Scholar
  142. 142.
    A. Larsson and B. Oberg, Antimicrob. Agents Chemother. 19: 927 (1981).CrossRefPubMedGoogle Scholar
  143. 143.
    P. Furman and P.V. McGuirt, Antimicrob. Agents Chemother. 23: 332 (1983).CrossRefPubMedGoogle Scholar
  144. 144.
    B.M. Colby, J.E. Shaw, G.B. Elion and J.S. Pagano, J. Virol. 34: 560 (1980).PubMedGoogle Scholar
  145. 145.
    J.A. Fyfe, P.M. Keller, P.A. Furman, R.L. Miller and G.B. Elion, J. Biol. Chem. 253: 8721 (1978).PubMedGoogle Scholar
  146. 146.
    B.A. Larder and G. Darby, J. Virol. 42: 649 (1982).PubMedGoogle Scholar
  147. 147.
    P.A. Furman, P. deMiranda, M.H. St. Clair and G.B. Elion, Antimicrob. Agents Chemother. 20: 518 (1981).CrossRefPubMedGoogle Scholar
  148. 148.
    W.H. Miller and R.L. Miller, J. Biol. Chem. 255: 7204 (1980).PubMedGoogle Scholar
  149. 149.
    M.S. Chen, J. Walker and W.H. Prusoff, J. Biol. Chem. 254: 10747 (1979).PubMedGoogle Scholar
  150. 150.
    W.H. Miller and R.L. Miller, Bíochem. Pharmacol. 31: 3879 (1982).CrossRefPubMedGoogle Scholar
  151. 151.
    P. deMiranda, S.S. Good, 0.L. Laskin, H.C. Krasny, J.D. Connor and P.S. Lietman, Clin. Pharmacol. Ther. 30: 662 (1981).CrossRefGoogle Scholar
  152. 152.
    P.A. Furman, P.V. McGuirt, P.M. Keller, J.A. Fyfe and G.B. Elion, Virology 102: 420 (1980).CrossRefPubMedGoogle Scholar
  153. 153.
    W.H. Burns, J.R. Wingard, W.J. Bender and R. Saral, J. Virol. 39: 889 (1981).PubMedGoogle Scholar
  154. 154.
    B.M. Colby, P.A. Furman, J.E. Shaw, G.B. Elion and J.S. Pagano, J. Virol. 38: 606 (1981).PubMedGoogle Scholar
  155. 155.
    M.H. St. Clair, P.A. Furman, C.M. Lubbers and G.B. Elion, Antimicrob. Agents Chemother. 18: 741 (1980).CrossRefGoogle Scholar
  156. 156.
    D. Derse, Y.-C. Cheng, P.A. Furman, M.H. St. Clair and G.B. Elion, J. Biol. Chem. 256: 11447 (1981).PubMedGoogle Scholar
  157. 157.
    A.K. Datta, B.M. Colby, J.E. Shaw and J.S. Pagano, Proc. Natl. Acad. Sci. USA 77: 4163 (1980).CrossRefGoogle Scholar
  158. 158.
    H.S. Allaudeen, J. Descamps and R.K. Sehgal, Antiviral Res. 2: 123 (1982).CrossRefPubMedGoogle Scholar
  159. 159.
    P.V. McGuirt and P.A. Furman, Amer. J. Med. 73: 67 (1982).CrossRefPubMedGoogle Scholar
  160. 160.
    K. Nakayama, J.L. Ruth and Y.-C. Cheng, J. Virol. 43: 325 (1982).PubMedGoogle Scholar
  161. 161.
    P.A. Furman, C.V. Lambe and D.J. Nelson, Amer. J. Med. 73: 14 (1982).CrossRefPubMedGoogle Scholar
  162. 162.
    H.J. Field and G. Darby, Antimicrob. Agents Chemother. 17: 209 (1980).CrossRefPubMedGoogle Scholar
  163. 163.
    C.S. Crumpacker, L.E. Schnipper, P. Chartrand and K.W. Knopf, Amer. J. Med. 73: 361 (1982).CrossRefPubMedGoogle Scholar
  164. 164.
    K.K. Biron, J.A. Fyfe, J.E. Noblin and G.B. Elion, Amer. J. Med. 73: 383 (1982).CrossRefPubMedGoogle Scholar
  165. 165.
    H.J. Field, Antimicrob. Agents Chemother. 21: 744 (1982).CrossRefGoogle Scholar
  166. 166.
    R.F. Schníazi, J. Peters, C.C. Williams, D. Chance and A.J. Nahmías, Antimicrob. Agents Chemother. 22: 499 (1982).CrossRefGoogle Scholar
  167. 167.
    D.S. Paris and J.E. Harrington, Antimicrob. Agents Chemother. 22: 71 (1982).CrossRefGoogle Scholar
  168. 168.
    C.S. Crumpacker, L.E. Schnipper, S.I. Marlowe, P.N. Kowalsky, B.J. Hershey and M.J. Levin, New Engl. J. Med. 306: 343 (1982).CrossRefPubMedGoogle Scholar
  169. 169.
    H. Field, A. McMillan and G. Darby, J. Infect. Dis. 143: 281 (1981).CrossRefPubMedGoogle Scholar
  170. 170.
    C.D. Sibrack, L.T. Gutman, C.M. Wilfert, C. McLaren, M.H. St. Clair, P.M. Keller and D.W. Barry, J. Infect. Dis. 146: 673 (1982).CrossRefPubMedGoogle Scholar
  171. 171.
    T. Hovi, Med. Biol. 60: 165 (1982).PubMedGoogle Scholar
  172. 172.
    R.B. Tenser, R.L. Miller and F. Rapp, Science 205: 915 (1979).CrossRefPubMedGoogle Scholar
  173. 173.
    H.J. Field, J.R. Anderson and P. Wildy, J. Gen. Virol. 59: 91 (1982).CrossRefPubMedGoogle Scholar
  174. 174.
    D.M. Coen and P.A. Schaffer, Proc. Natl. Acad. Sci. USA 77: 2265 (1980).CrossRefPubMedGoogle Scholar
  175. 175.
    B.A. Larder, D. Derse, Y.-C. Cheng and G. Darby, J. Biol. Chem. 258: 2027 (1983).PubMedGoogle Scholar
  176. 176.
    B.A. Larder, Y.-C. Cheng and G. Darby, J. Gen. Virol. 64: 523 (1983).CrossRefPubMedGoogle Scholar
  177. 177.
    P.A. Furman, D.M. Coen, M.H. St. Clair and P.A. Schaffer, J. Virol. 40: 936 (1981).PubMedGoogle Scholar
  178. 178.
    K.O. Smith, K.S. Galloway, W.L. Kennell, K.K. Ogilvie and B.K. Radatus, Antimicrob. Agents Chemother. 22: 55 (1982).CrossRefPubMedGoogle Scholar
  179. 179.
    W.T. Ashton, J.D. Karkas, A.K. Field and R.L. Tolman, Biochem. Biophys. Res. Commun. 108: 1716 (1982).CrossRefPubMedGoogle Scholar
  180. 180.
    D.F. Smee, J.C. Martin, J.P.H. Verheyden and T.R. Mathews, Antimicrob. Agents Chemother. 23: 676 (1983).CrossRefPubMedGoogle Scholar
  181. 181.
    Y.-C. Cheng, E.-S. Huang, J.-C. Lin, E.-C. Mar, J.S. Pagano and G. Dutschman, Proc. Natl. Acad. Sci. USA in press.Google Scholar
  182. 182.
    J.C. Martin, C.A. Dvorak, D.F. Smee, T.R. Mathews and J.P.H. Verheyden, J. Med. Chem. in press (1983).Google Scholar
  183. 183.
    K.O. Smith, K.S. Galloway, K.K. Ogilvie and U.O. Cheriyan, Antimicrob. Agents Chemother. 22: 1026 (1982).CrossRefPubMedGoogle Scholar
  184. 184.
    A. Larsson, B. Öberg, S. Alenius, G.-E. Hagberg, N.-G. Johansson, B. Lindborg and G. Stening, Antimicrob. Agents Chemother. 23: 664 (1983).CrossRefPubMedGoogle Scholar
  185. 185.
    E. DeClercq and A. Holy, J. Med. Chem. 22: 510 (1979).CrossRefGoogle Scholar
  186. 186.
    E. De Clercq, J. Descamps, P. De Somer and A. Holy, Science 200: 563 (1978).CrossRefGoogle Scholar
  187. 187.
    R. Jelinek, A. Holy and I. Votruba, Teratol. 24: 267 (1981).CrossRefGoogle Scholar
  188. 188.
    B. Rada, M. Dragun, I. Votruba and A. Holy, Acta. Virol. 24: 433 (1980).PubMedGoogle Scholar
  189. 189.
    B. Rada and A. Holy, Chemother. 26: 184 (1980).CrossRefGoogle Scholar
  190. 190.
    A. Holy and A. Cihak, Biochem. Pharmacol. 30: 2359 (1981).CrossRefPubMedGoogle Scholar
  191. 191.
    A. Holy, I. Votruba and E. De Clercq, Collect. Czech. Chem. Commun. 47: 1392 (1982).CrossRefGoogle Scholar
  192. 192.
    T.W. North and L.O’Connor, E. Abushanab and R.P. Panzica, Biochem. Pharmacol. in press (1983).Google Scholar
  193. 193.
    R.W. Sidwell, R.K. Robins and I.W. Hillyard, Pharmacol. Therap. 6: 123 (1979).CrossRefGoogle Scholar
  194. 194.
    R.A. Smith and W. Kirkpatrick, eds. “Ribavirin, A Broad Spectrum Antiviral Agent,” Academic Press, New York (1980) 237 pp.Google Scholar
  195. 195.
    T.-W. Chang and R.C. Heel, Drugs 22: 111 (1981).CrossRefPubMedGoogle Scholar
  196. 196.
    S.M. Bierman, W. Kirkpatrick and H. Fernandez, Chemother. 27: 139 (1981).CrossRefGoogle Scholar
  197. 197.
    S.A. Patki and P. Gupta, Chemother. 28: 298 (1982).CrossRefGoogle Scholar
  198. 198.
    V. Knight, S.Z. Wilson, J.M. Quarles, S.E. Greggs, H.W. McClung, B.K. Waters, R.W. Cameron, J.M. Zerwas and R.B. Couch, Lancet 945 (1981).Google Scholar
  199. 199.
    H.W. McClung, V. Knight, B.E. Gilbert, S.Z. Wilson, J.M. Quarles and G.W. Divine, J. Amer. Med. Assn. 249: 2671 (1983).CrossRefGoogle Scholar
  200. 200.
    C.B. Hall, E.E. Walsh, J.F. Hrusak, R.F. Betts and W.J. Hall, J. Amer. Med Assn. 249: 2666 (1983).CrossRefGoogle Scholar
  201. 201.
    R.C. Willis, D.A. Carson and J.E. Seegmiller, Proc. Natl. Acad. Sci. USA 75: 3042 (1978).CrossRefPubMedGoogle Scholar
  202. 202.
    J.C. Drach, M.A. Thomas, J.W. Barnett, S.H. Smith and C. Shipman, Jr., Science 212: 549 (1981).CrossRefPubMedGoogle Scholar
  203. 203.
    B. Oberg and E. Helgstrand in: “Current Chemotherapy (Proc. 10th Intl. Congr. Chemother., Zurich),” W. Siegenthaler and R. Lüthy eds., ASM, Washington, D.C. (1977) p. 332.Google Scholar
  204. 204.
    B. Eriksson and B. Öberg, Antimicrob. Agents Chemother. 11: 946 (1977).CrossRefPubMedGoogle Scholar
  205. 205.
    D.G. Streeter, J.T. Witkowski, G.P. Khare, R.W. Sidwell, R.J. Bauer, R.K. Robins and L.N. Simon, Proc. Natl. Acad. Sci. USA 70: 1174 (1973).CrossRefPubMedGoogle Scholar
  206. 206.
    D.A. Cooney, H.N. Jayaram, G. Gebeyehu, C.R. Betts, J.A. Kelly, V.E. Marquez and D.G. Johns, Biochem. Pharmacol. 31: 2133 (1982).CrossRefPubMedGoogle Scholar
  207. 207.
    R.K. Robins, P.O. Srivastava, V.L. Narayanan, J. Plowman and D.K. Paull, J. Med. Chem. 25: 107 (1982).CrossRefPubMedGoogle Scholar
  208. 208.
    B.B. Goswami, E. Borek, O.K. Sharma, J. Fujitaki and R.A. Smith, Biochem. Biophys. Res. Commun. 89: 830 (1979).CrossRefPubMedGoogle Scholar
  209. 209.
    L.B. Allen and C.M. Fingal, Antimicrob. Agents Chemother. 12: 120 (1977).CrossRefPubMedGoogle Scholar
  210. 210.
    R.K. Robins, G.R. Revankar, P.C. Srivastava, J. Kirsi, J.A. North, B. Murray and P.A., McKernan, Amer. Chem. Soc. Div. Carb. Chem., 185th Natl. Mtg., Seattle (1983) Abst. 45.Google Scholar
  211. 211.
    L.B. Allen, J.H. Huffman, P.D. Cook, R.B. Meyer, Jr., R.K. Robins and R.W. Sidwell, Antimicrob. Agents Chemother. 12: 114 (1977).CrossRefPubMedGoogle Scholar
  212. 212.
    D.G. Streeter and H.H.P. Koyama, Biochem. Pharmacol. 25: 2413 (1976).CrossRefPubMedGoogle Scholar
  213. 213.
    B. Kojic-Prodic, Z. Ruzic-Toros, L. Golic, B. Brdar and J. Kobe, Biochim. Biophys. Acta 698: 105 (1982).CrossRefPubMedGoogle Scholar
  214. 214.
    J.C. Drach, C.M. Reinke, S.H. Smith and P.D. Cook, 21st Inter-science Conf. Antimicrob. Agents Chemother., Chicago (1981) Abst. 872.Google Scholar
  215. 215.
    J.A. Montgomery, S.J. Clayton and P.K. Chiang, J. Med. Chem. 25: 96 (1982).CrossRefPubMedGoogle Scholar
  216. 216.
    P.K. Chiang, H.H. Richards and G.L. Cantoni, Molec. Pharmacol. 13: 939 (1977).Google Scholar
  217. 217.
    J.P. Bader, N.R. Brown, P.K. Chiang and G.L. Cantoni, Virology 89: 494 (1978).CrossRefPubMedGoogle Scholar
  218. 218.
    A.J. Bodner, G.L. Cantoni and P.K. Chiang, Biochem. Biophys. Res. Commun. 98: 476 (1981).CrossRefPubMedGoogle Scholar
  219. 219.
    P.K. Chiang and G.L. Cantoni, Biochem. Pharmacol. 28:1897 (1979)Google Scholar
  220. 220.
    J.L. Medzihradsky, T.P. Zimmerman, G. Wolberg and G.B. Elion, J. Immunopharmacol. 4: 29 (1982).CrossRefPubMedGoogle Scholar
  221. 221.
    J.A. Montgomery, S.J. Clayton, H.J. Thomas, W.M. Shannon, G. Arnett, A.J. Bodnar, I.-K. Kion, G.L. Cantoni and P.K. Chiang, J. Med. Chem. 25: 626 (1982).CrossRefPubMedGoogle Scholar
  222. 222.
    P.K. Chiang, R.K. Gordon, N.D. Brown, E. DeClercq and J.A. Montgomery, Amer. Chem. Soc. Div. Med. Chem., 185th Natl. Mtg., Seattle (1983) Abst. 34.Google Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • John C. Drach
    • 1
  1. 1.School of DentistryUniversity of MichiganAnn ArborUSA

Personalised recommendations