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Competitive inhibitors of human immunodeficiency virus reverse transcriptase

  • Perspectives
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Perspectives in Drug Discovery and Design

Summary

Nucleoside analogs continue to provide a rich source of potent and selective anti-HIV agents. The 5′-triphosphate forms of the clinically useful nucleosides are competitive inhibitors of retroviral reverse transcriptases and can result in the termination of chain elongation of proviral DNA. The function of viral reverse transcriptases and the mechanism of action of various compounds against HIV and hepatitis B virus are discussed. Insights in drug combination and viral resistance to nucleoside analogs are also provided with emphasis on novel enantiomers of nucleosides with the unusuall-configuration.

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References

  1. Cann, A.J. and Karn, J., AIDS, 3 (1989) S19.

  2. Haseltine, W.A., J. Acq. Imm. Defic. Syndr., 2 (1989) 311.

    Google Scholar 

  3. Haseltine, W.A., FASEB J, 5 (1991) 2349.

    Google Scholar 

  4. Berzofsky, J.A., J. Acq. Imm. Defic. Syndr., 4 (1991) 451.

    Google Scholar 

  5. Koff, W.C., Hosp. Pract., 26 (1991) 99.

    Google Scholar 

  6. Connolly, K.J. and Hammer, S.M., Antimicrob. Agents Chemother., 36 (1992) 245.

    Google Scholar 

  7. Connolly, K.J. and Hammer, S.M., Antimicrob. Agents Chemother., 36 (1992) 509.

    Google Scholar 

  8. De Clercq, E., AIDS Res. Hum. Retroviruses, 8 (1992) 119.

    Google Scholar 

  9. Mitsuya, H., Yarchoan, R. and Broder, S., Science, 249 (1990) 1533.

    Google Scholar 

  10. Schinazi, R.F., Mead, J.R. and Feorino, P.M., AIDS Res. Hum. Retroviruses, 8 (1992) 963.

    Google Scholar 

  11. Schinazi, R.F., In Chou, T.C. and Rideout, D.C. (Eds.) Molecular Mechanisms of Chemotherapeutic Synergism, Potentiation, and Antagonism, Academic Press, Orlando, 1991, pp. 110–181.

    Google Scholar 

  12. Sommadossi, J.-P., Clin. Infect. Dis., 16 (1993) S7.

    Google Scholar 

  13. Schinazi, R.F., Lloyd, R., Oswald, B. and Manning, C., Antiviral Res., 15 (1991) 97.

    Google Scholar 

  14. Buckheit, Jr., R.W., and Swanstrom, R., AIDS Res. Hum. Retroviruses, 7 (1991) 295.

    Google Scholar 

  15. Koenig, S., Gendelman, H., Orenstein, J., Dal Canto, M., Pezeshkpour, G., Yungbluth, M., Janotta, F., Aksamit, A., Martin, M. and Fauci, A., Science, 233 (1986) 1089.

    Google Scholar 

  16. Pantaleo, G., Graziosi, C., Demarest, J.F., Butini, L., Montroni, M., Fox, C.H., Orenstein, J.M., Kotler, D.P. and Fauci, A.S., Nature, 362 (1993) 355.

    Google Scholar 

  17. De Clercq, E., J. Acq. Imm. Defic. Syndr., 4 (1991) 207.

    Google Scholar 

  18. Hirsch, M., J. Infect. Dis., 161 (1990) 845.

    Google Scholar 

  19. Sodroski, J., Goh, W., Rosen, C., Dayton, A., Terwilliger, E. and Haseltine, W., Nature, 321 (1986) 412.

    Google Scholar 

  20. Feorino, P., Butera, S.T., Folks, T.M. and Schinazi, R.F., Antiviral Chem. Chemother., 4 (1993) 55.

    Google Scholar 

  21. Hsu, M.C., Schutt, A.D., Holly, M., Slice, L.W., Sherman, M.I., Richman, D.D., Potash, M.J. and Volsky, D.J., Biochem. Soc. Trans., 20 (1992) 525.

    Google Scholar 

  22. Robins, T. and Plattner, J., J. Acq. Imm. Defic. Syndr., 6 (1993) 162.

    Google Scholar 

  23. Sarver, N., Black, R.J., Bridges, S. and Chrisey, L., AIDS Res. Hum. Retroviruses, 8 (1992) 659.

    Google Scholar 

  24. Saag, M.S., Hosp. Pract., 27 (1992) 26.

    Google Scholar 

  25. Sommadossi, J.-P., Zhu, Z., Carlisle, R., Xie, M.-Y. and Weidner, D.A., NY Acad. Sci., 616 (1990) 356.

    Google Scholar 

  26. Otto, M.J., Garber, S., Winslow, D., Cheng, Y.-S.E., Reid, C.D., Aldrich, P. and Jadhav, R.K., VIII International Conference on AIDS, Amsterdam, 1992.

  27. Patterson, C.E., Cheng, Y.-S.E., Buckery, R., Otto, M.J. and Winslow, D.L., VIII International Conference on AIDS, Amsterdam, 1992.

  28. Richman, D., Shih, C.K., Lowy, I., Rose, J., Prodanovich, P., Goff, S. and Griffin, J., Proc. Natl. Acad. Sci. USA, 88 (1991) 11241.

    Google Scholar 

  29. Richman, D., AIDS Res. Hum. Retroviruses, 8 (1992) 1065.

    Google Scholar 

  30. Périgaud, C., Gosselin, G. and Imbach, J.-L., Nucleosides Nucleotides, 11 (1992) 903.

    Google Scholar 

  31. Li, P., Kuiper, L.J., Stephenson, A.J. and Burrell, C.J., J. Gen. Virol., 73 (1992) 955.

    Google Scholar 

  32. Buckheit, Jr., R.W., Germany-Decker, J., Qualls-Goodwin, K., Bowdon, B.J. and Shannon, W.M., Proc. Natl. Acad. Sci. USA, 89 (1992) 8361.

    Google Scholar 

  33. Temin, H.M. and Baltimore, D., Adv. Virus Res., 17 (1972) 129.

    Google Scholar 

  34. Chandra, P., Ebener, U. and Götz, A., FEBS Lett., 3 (1975) 10.

    Google Scholar 

  35. Gerard, G.F. and Grandgenett, D., In Stephenson, J.R. (Ed.) Molecular Biology of RNA Tumor Viruses, Academic Press, New York, 1980, pp. 345–394.

    Google Scholar 

  36. Ben-Artzi, H., Zeelon, E., Gorecki, M. and Panet, A., Proc. Natl. Acad. Sci. USA, 89 (1992) 927.

    Google Scholar 

  37. Hostomsky, Z., Hudson, G.O., Rahmati, S. and Hostomska, Z., Nucleic Acids Res., 20 (1992) 5819.

    Google Scholar 

  38. Peliska, J.A. and Benkovic, S.J., Science, 258 (1992) 1112.

    Google Scholar 

  39. Majumdar, C., Abbotts, J., Broder, S. and Wilson, S.H., J. Biol. Chem., 263 (1988) 15657.

    Google Scholar 

  40. Hahn, B.H., Shaw, G.M., Taylor, M.E., Redfield, R.R., et al., Science, 232 (1986) 1548.

    PubMed  Google Scholar 

  41. Preston, B.D., Poiesz, B.J. and Loeb, L.A., Science, 242 (1988) 1168.

    PubMed  Google Scholar 

  42. Roberts, J.D., Bebenek, K. and Kunkel, T.A., Science, 242 (1988) 1171.

    PubMed  Google Scholar 

  43. Ricchetti, M. and Buc, H., EMBO J., 9 (1990) 1583.

    Google Scholar 

  44. Bebenek, K., Abbotts, J., Roberts, J.D., Wilson, S.H. and Kunkel, T.A., J. Biol. Chem., 264 (1989) 16948.

    Google Scholar 

  45. Schuitemaker, H., Koot, M., Kootstra, N.A., Dercksen, M.W., de Goede, R.E.Y., van Steenwijk, R.P.; Lange, J.M., Schattenkerk, J.K., Miedema, F. and Tersmette, M., J. irol. 66 (1992) 1354.

    Google Scholar 

  46. Summers, J. and Mason, W., Cell, 29 (1982) 403.

    Google Scholar 

  47. Tiollais, P. and Buendia, M.-A., Sci. Am., (1991) 116.

  48. Bavand, M.R. and Laub, O., J. Virol., 62 (1988) 626.

    Google Scholar 

  49. McLachlan, A., Molecular Biology of the Hepatitis B Virus, CRC Press, Boca Raton, 1991.

    Google Scholar 

  50. Chandra, P., Vogel, A. and Gerber, T., Cancer Res., 4S (Suppl) (1985) 4677s.

  51. Chandra, P., Steel, L.K., Ebener, U., Wolterdorf, M., Laube, H., Kornhuber, B., Mildner, B. and Götz, A., Pharmacol. Ther., 1 (1977) 231.

    Google Scholar 

  52. Tan, C.-K., Civil, R., Mian, A.M., So, A.G. and Downey, K.M., Biochem., 30 (1991) 4831.

    Google Scholar 

  53. Hopkins, S., Furman, P.A. and Painter, G.R., Biochem. Biophys. Res. Commun., 163 (1989) 106.

    Google Scholar 

  54. Goody, R.S., Müller, B. and Restle, T., FEBS, 291 (1991) 1.

    Google Scholar 

  55. Painter, G.R., Wright, L.L., Hopkins, S. and Furman, P.A., J. Biol. Chem., 266 (1991) 19362.

    Google Scholar 

  56. Furman, P.A., Painter, G., Wilson, J.E., Cheng, N. and Hopkins, S., Proc. Natl. Acad. Sci. USA, 88 (1991) 6013.

    Google Scholar 

  57. Merluzzi, V.J., Hargrave, K.D., Labadia, M., Grozinger, K., Skoog, M., Wu, J.C., Shih, C.-K., Eckner, K., Hattox, S., Adams, J., Roshthal, A.S., Faanes, R., Eckner, R.J., Koup, R.A. and Sullivan, J.L., Science, 250 (1990) 1411.

    Google Scholar 

  58. Pauwels, R., Andries, K., Desmyter, J., Schols, D., Kukla, M.J., Breslin, H.J., Raeymaeckers, A., Van Gelder, J., Woestenborghs, R., Heykants, J., Schellekens, K., Janssen, M.A.C., De Clercq, E. and Janssen, P.A.J., Nature, 343 (1990) 470.

    Google Scholar 

  59. Ma, Q.-F., Bathurst, I.C., Barr, P.J. and Kenyon, G.L., J. Med. Chem., 35 (1992) 1938.

    Google Scholar 

  60. Cheng, Y.-C., Dutschman, G.E., Bastow, K.F., Sarngadharan, M.G. and Ting, R.Y.C., J. Biol. Chem., 262 (1987) 2187.

    Google Scholar 

  61. Eriksson, B., Vrang, L., Bazin, H., Chattopadhyaya, J. and Öberg, B., Antimicrob. Agents Chemother., 31 (1987) 600.

    Google Scholar 

  62. Bazin, H., Chattopadhyaya, J., Datema, R., Gilljam, G., Johansson, N.G., Koshida, R., Oberg, B., Stening, G., Vrang, L., Wahren, B. and Wu, J.-C., Biochem. Pharmacol., 38 (1989) 109.

    Google Scholar 

  63. North, T.W., Cronn, R.C., Remington, K.M. and Tandberg, R.T., Antimicrob. Agents Chemother., 34 (1990) 1505.

    Google Scholar 

  64. Mathes, L.E., Polas, P.J., Hayes, K.A., Swenson, C.L., Johnson, S. and Kociba, G.J., Antimicrob. Agents Chemother., 36 (1992) 2715.

    Google Scholar 

  65. Hayes, K.A., Lafrado, L.J., Erickson, J.G., Marr, J.M. and Mathes, L.E., J. Acq. Imm. Defic. Syndr., 6 (1993) 127.

    Google Scholar 

  66. Selleseth, D.W., Johnson, C.M., Childers, T.A., Ellis, M.N., Tompkins, M. and Tompkins, W.A.F., Proceedings of Innovations in Therapy of Human Viral Diseases, December 7–9, 1992, Research Triangle Park, NC, (Abstr. p. 18).

  67. Humber, D.C., Jones, M.F., Payne, J.J., Ramsey, M.V.J., Zacharie, B., Jin, H., Siddiqui, A., Evans, C.A., Tse, H.L.A. and Mansour, T.S., Tetrahedron Lett., 33 (1992) 4625.

    Google Scholar 

  68. Van Roey, P., Salerno, J.M., Duax, W.L., Chu, C.K., Ahn, M.K. and Schinazi, R.F., J. Am. Chem. Soc., 110 (1988) 2277.

    Google Scholar 

  69. Van Roey, P., Salerno, J.M., Chu, C.K. and Schinazi, R.F., Proc. Natl. Acad. Sci. USA, 86 (1989) 3929.

    Google Scholar 

  70. Van Roey, P. and Schinazi, R.F., Antiviral Chem. Chemother., 1 (1990) 93.

    Google Scholar 

  71. Van Roey, P., Pangborn, W.A., Painter, G. and Liotta, D.C., Antiviral Chem. Chemother., submitted.

  72. Taylor, E.W., Van Roey, P., Schinazi, R.F. and Chu, C.K., Antiviral Chem. Chemother., 1 (1990) 163.

    Google Scholar 

  73. Kim, H.O., Ahn, S.K., Alves, A.J., Beach, J.W., Jeong, L.S., Choi, B.G., Van Roey, P., Schinazi, R.F. and Chu, C.K., J. Med. Chem., 35 (1992) 1987.

    Google Scholar 

  74. Chu, C.K., Ahn, S.K., Kim, H.O., Beach, J.W., Alves, A.J., Jeong, L.S., Islam, Q., Van Roey, P. and Schinazi, R.F., Tetrahedron Lett., 32 (1991) 3791.

    Google Scholar 

  75. Sundaralingam, M., In Sundaralingam, M. and Rao, S.T. (Eds.) Structure and Conformation of Nucleic Acid and Protein-Nucleic Acid Interactions, University Park Press, Baltimore, 1975, pp. 487–536.

    Google Scholar 

  76. Saenger, W., Principles of Nucleic Acid Structure, Springer, New York, 1984.

    Google Scholar 

  77. Lin, T.-S., Yang, J.-H., Liu, M.-C., Shen, Z.-Y., Cheng, Y.-C., Prusoff, W.H., Birnbaum, G.I., Giziewicz, J., Ghazzouli, I., Brankowan, V., Feng, J.-S. and Hsiung, G.-D., J. Med. Chem., 34 (1991) 693.

    Google Scholar 

  78. Crabbe, M.J.C. and Falkingbridge, S.S., AIDS Res. Hum. Retroviruses, 7 (1991) 261.

    Google Scholar 

  79. Horwitz, J.P., Chua, J. and Noel, M., J. Org. Chem., 29 (1984) 2076.

    Google Scholar 

  80. Krieg, C.J., Ostertag, W., Clauss, U., Pragnell, I.B., Swetly, P., Roesler, G. and Weimann, B.J., Cell Res., 116 (1978) 21.

    Google Scholar 

  81. Ostertag, W., Cole, T., Crozier, T., Gaedicke, G., Kind, J., Kluge, N., Krieg, J.C., Roesler, G., Steinheider, G., Weinmann, B.J. and Dube, S.K., Differentiation and Control of Malignancy of Tumor Cells. Proceedings of the 4th International Symposium Princess Takamatsu Cancer Research Fund, 1973.

  82. Ostertag, W., Roesler, G., Krieg, C.J., Kind, J., Cole, T., Crozier, T., Gaedicke, G., Steinheider, G., Kluge, N. and Dube, S., Proc. Natl. Acad. Sci. USA, 71 (1974) 4980.

    Google Scholar 

  83. Mitsuya, H., Weinhold, K.J., Furman, P.A., St. Clair, M.H., Lehrman, S.N., Gallo, R.C., Bolognesi, D., Barry, D.W. and Broder, S., Proc. Natl. Acad. Sci. USA, 82 (1985) 7096.

    Google Scholar 

  84. Furman, P.A., Fyle, J.A., St. Clair, M.H., Weinhold, K., Rideout, J.L., Freeman, G.A., Nusinoff-Lehrman, S., Bolognesi, D.P., Broder, S., Mitsuya, H. and Barry, D.W., Proc. Natl. Acad. Sci. USA, 83 (1986) 8333.

    Google Scholar 

  85. Nickel, W., Austermann, S., Bialek, G. and Grosse, F., J. Biol. Chem., 267 (1992) 848.

    Google Scholar 

  86. König, H., Behr, E., Löwer, J. and Kurth, R., Antimicrob. Agents Chemother., 33 (1989) 2109.

    Google Scholar 

  87. Lutton, J.D., Mathew, A., Levere, R.D. and Abraham, N.G., Am. J. Hematol., 35 (1990) 1.

    Google Scholar 

  88. Weidner, D.S. and Somadossi, J.-P., Mol. Pharmacol., 38 (1990) 797.

    Google Scholar 

  89. Elwell, L.P., Ferone, R., Freeman, G.A., Fyfe, J.A., Hill, J.A., Ray, P.H., Richards, C.A., Singer, S.C., Nick, V.B., Rideout, J.L. and Zimmerman, T.P., Antimicrob. Agents Chemother., 31 (1987) 274.

    Google Scholar 

  90. Huang, P., Farquhar, D. and Plunkett, W., J. Biol. Chem., 265 (1990) 11914.

    Google Scholar 

  91. St. Clair, M.H., Richards, C.A., Spector, T., Weinhold, K.J., Miller, W.H., Langlois, A.J. and Furman, P.A., Antimicrob. Agents Chemother., 31 (1987) 1972.

    Google Scholar 

  92. Eriksson, B.F.H., Chu, C.K. and Schinazi, R.F., Antimicrob. Agents Chemother., 33 (1989) 1729.

    Google Scholar 

  93. Kedar, P.S., Abbots, J., Kovács, T., Lesiak, K., Torrence, P. and Wilson, S.H., Biochemistry, 29 (1990) 3603.

    Google Scholar 

  94. Huber, H.E., McCoy, J.M., Seehra, J.S. and Richardson, C.C., J. Biol. Chem., 264 (1989) 4669.

    Google Scholar 

  95. Reardon, J.E., Furfine, E.S. and Cheng, N., J. Biol. Chem., 266 (1991) 14128.

    Google Scholar 

  96. Lacey, S.F., Reardon, J.E., Furfine, E.S., Kunkel, T.A., Bebenek, K., Eckert, K.A., Kemp, S.D. and Larder, B.A., J. Biol. Chem., 267 (1992) 15789.

    Google Scholar 

  97. Schinazi, R.F., Chu, C.K., Ahn, M.K., Sommadossi, J.P. and McClure, H., J. Cell. Biochem., 11 (1987) 405.

    Google Scholar 

  98. Chu, C.K., Schinazi, R.F., Ahn, M.K., Ullas, G.V. and Gu, Z.P., J. Med. Chem., 32 (1989) 612.

    Google Scholar 

  99. Zhu, Z., Schinazi, R.F., Chu, C.K., Williams, G.J., Colby, C.B. and Sommadossi, J.P., Mol. Pharmacol., 38 (1990) 929.

    Google Scholar 

  100. Boudinot, F.D., Schinazi, R.F., Gallo, J.M., McClure, H.M., Anderson, D.C., Doshi, K.J., Kambhampathi, P.C. and Chu, C.K., AIDS Res. Hum. Retroviruses, 6 (1990) 219.

    Google Scholar 

  101. Schinazi, R.F., Chu, C.K., Eriksson, B.F., Sommadossi, J.P., Doshi, K.J., Boudinot, F.D., Oswald, B. and McClure, H.M., Ann. NY Acad. Sci., 616 (1990) 385.

    Google Scholar 

  102. Schinazi, R.F., Oswald, B., Zhu, Z., Chu, C.K. and Sommadossi, J.P., Conference on Advances in Molecular Biology and Targeted Treatments for AIDS, Washington DC, 1990.

  103. Maag, H. and Rydzewski, R.M., J. Org. Chem., 57 (1992) 5823.

    Google Scholar 

  104. Maag, H., Rydzewski, R.M., McRoberts, M.J., Crawford-Ruth, D., Verheyden, P.H. and Prisbe, E.J., J. Med. Chem., 35 (1992) 1440.

    Google Scholar 

  105. Chen, M.S., Suttmann, R.T., Wu, J.C. and Prisbe, E.J., J. Biol. Chem., 267 (1992) 257.

    Google Scholar 

  106. Chen, M.S., Suttmann, R., Bach, C., Wu, J.C., Prisbe, E.J., McRoberts, M.J. and Crawford-Ruth, D., Antiviral Res., 15 (1991) 91 [Abstr. 87].

    Google Scholar 

  107. Mitsuya, H. and Broder, S., Nature, 325 (1987) 773.

    Google Scholar 

  108. Mitsuya, H. and Broder, S., Proc. Natl. Acad. Sci. USA, 82 (1986) 1911.

    Google Scholar 

  109. Waqar, M.A., Evans, M.J., Manly, K.F., Hughes, R.G. and Huberman, J.A., J. Cell. Physiol., 121 (1984) 402.

    Google Scholar 

  110. Balzarini, J., Cooney, D.A., Dalal, M., Kang, G.J., Cupp, J.E., De Clercq, E., Broder, S. and Johns, D.G., Mol. Pharmacol., 32 (1987) 798.

    Google Scholar 

  111. Cooney, D.A., Dalal, M., Mitsuya, H., McMahon, J.B., Nadkarni, M., Balzarini, J., Broder, S. and Johns, D.G., Biochem. Pharmacol., 35 (1986) 2065.

    Google Scholar 

  112. Starnes, M.C. and Cheng, Y.C., Virus Genes, 2 (1988) 241.

    Google Scholar 

  113. Hao, Z., Cooney, D.A., Hartman, N.R., Perno, C.F., Fridland, A., DeVico, A.L.S., Broder, S. and Johns, D.G., Mol. Pharmacol., 34 (1988) 431.

    Google Scholar 

  114. Johnson, M.A., Ahluwalia, G., Connelly, M.C., Cooney, D.A., Broder, S., Johns, D.G. and Fridland, A., J. Biol. Chem., 263 (1988) 15354.

    Google Scholar 

  115. Chu, C.K., Ullas, G.V., Jeong, S., Ahn, S.K., Doboszewski, B., Lin, Z.X., Beach, J.W. and Schinazi, R.F., J. Med. Chem., 33 (1990) 1553.

    Google Scholar 

  116. Marquez, V.E., Tseng, C.K.-H., Mitsuya, H., Aoki, S., Kelly, J.A., Ford, Jr., H., Roth, J.S., Broder, S., Johns, D.G. and Driscoll, J.S., J. Med. Chem., 33 (1990) 978.

    Google Scholar 

  117. Karlsson, A., Reichard, P. and Eckstein, F., Biochem. Biophys. Res. Commun., 166 (1990) 273.

    Google Scholar 

  118. Ahluwalia, G., Cooney, D.A., Bondoc, Jr., L.L., Currens, M.J., Ford, H., Johns, D.G., Mitsuya, H. and Fridland, A., Biochem. Biophys. Res. Commun., 171 (1990) 1297.

    Google Scholar 

  119. Parker, W.B., White, E.L., Shaddix, S.C., Ross, L.J., Buckheit, Jr., R.W., Germany, J.M., Secrist, J.A.I., Vince, R. and Shannon, W.M., J. Biol. Chem., 266 (1991) 1754.

    Google Scholar 

  120. Balzarini, J., Herdewijn, P. and DeClercq, E., Int. Conf. AIDS, 4 (1989) 554.

    Google Scholar 

  121. Lin, T.-S., Schinazi, R.F. and Prusoff, W.H., Biochem. Pharmacol., 36 (1987) 2713.

    Google Scholar 

  122. Lin, T.-S., Schinazi, R., Chen, M., Kinney-Thomas, E. and Prusoff, W., Biochem. Pharmacol., 36 (1987) 311.

    Google Scholar 

  123. Herdewijn, P., Balzarini, J., DeClercq, E., Pauwels, R., Baba, M., Broder, S. and Vanderhaeghe, H., J. Med. Chem., 30 (1987) 1270.

    Google Scholar 

  124. Mansuri, M.M., Starrett, Jr., J.E., Ghazzouli, I., Hitchcock, M.J.M., Sterzycki, R.Z., Brankovan, V.M., Lin, T.-S., August, E.M., Prusoff, W.J., Sommadossi, J.P. and Martin, J.C., J. Med. Chem., 32 (1989) 461.

    Google Scholar 

  125. Hamamoto, Y., Nakashima, H., Matsui, T., Matsuda, A., Ueda, T. and Yamamoto, N., Antimicrob. Agents Chemother., 31 (1987) 907.

    Google Scholar 

  126. Mansuri, M.M., Farina, V., Starrett, J.E., Benigni, D.A., Brankovan, V. and Martin, J.C., Bioorg. Med. Chem. Lett., 1 (1991) 65.

    Google Scholar 

  127. Schinazi, R., Boudinot, F., Doshi, K., Anderson, D. and McClure, H., Antimicrob. Agents Chemother., 34 (1990) 1214.

    Google Scholar 

  128. Sidwell, R.W., Hitchcock, M., Okleberry, K.M., Burger, R.A., Warren, R.P. and Morrey, J.D., Antiviral Res., 19 (1992) 313.

    Google Scholar 

  129. Yang, H., Patick, A., Franco, C., Drain, R. and Datema, R., J. Acq. Imm. Defic. Syndr., 4 (1991) 360.

    Google Scholar 

  130. Zhu, Z., Ho, H.-T., Hitchcock, M.J. and Sommadossi, J.-P., Biochem. Pharmacol., 39 (1990) R15.

    Google Scholar 

  131. Boudinot, F.D., Smith, S.G., Funderburg, E.D. and Schinazi, R.F., Antimicrob. Agents Chemother., 35 (1991) 747.

    Google Scholar 

  132. Hitchcock, M.J.M., Antiviral. Chem. Chemother., 2 (1991) 125.

    Google Scholar 

  133. Matthes, E., Lehmann, C., Scholz, D., Rosenthal, H.A. and Langen, P., Biochem. Biophys. Res. Commun., 153 (1988) 825.

    Google Scholar 

  134. Olofsson, S., Eriksson, S., Karlsson, A. and Oberg, B., Antiviral. Res., 19 (1992) 71.

    Google Scholar 

  135. Bergstrom, D.E., Mott, A.W., De Clercq, E., Balzarini, J. and Swartling, D.J., J. Med. Chem., 35 (1992) 3369.

    Google Scholar 

  136. Coates, J.A.V., Inggall, H.J., Pearson, B.A., Penn, C.R., Storer, R., Williamson, C. and Cameron, J.M., Antiviral Res., 15 (1991) 161.

    Google Scholar 

  137. Shannon, W.M., In Diasio, R.B. and Sommadossi, J.-P. (Eds.) Advances in Chemotherapy of AIDS, Pergamon Press, New York, 1990, pp. 75–95.

    Google Scholar 

  138. Vince, R., Hua, M., Brownell, J., Daluge, S., Lee, F.C., Shannon, W.M., Lavelle, G.C., Qualls, J., Weislow, O.S., Kiser, R., Canonico, P.G., Schultz, R.H., Narayanan, V.L., Mayo, J.G., Shoemaker, R.H. and Boyd, M.R., Biochem. Biophys. Res. Commun., 156 (1988) 1046.

    Google Scholar 

  139. Vince, R. and Hua, M., J. Med. Chem., 33 (1990) 17.

    Google Scholar 

  140. Orr, D.C., Figueiredo, H.T., Mo, C.-L., Penn, C.R. and Cameron, J.M., J. Biol. Chem., 267 (1992) 4177.

    Google Scholar 

  141. Vince, R. and Brownell, J., Biochem. Biophys. Res. Commun., 168 (1990) 912.

    Google Scholar 

  142. White, E.L., Parker, W.B., Macy, L.J., Shaddix, S.C., McCaleb, G., Secrist, J.A.I., Vince, R. and Shannon, W.M., Biochem. Biophys. Res. Commun., 161 (1989) 393.

    Google Scholar 

  143. Belleau, B., Dixit, D., Nguyen-Ba, N. and Kraus, L., V International Conference on AIDS, Montreal, 1989.

  144. Wainberg, M.A., Stern, M., Martel, R., Belleau, B. and Soudeyns, H., V International Conference on AIDS, Montreal, 1989.

  145. Soudeyns, H., Yao, X.-J., Gao, Q., Belleau, B., Kraus, J.-L., Nguyen-Ba, N., Spira, B. and Wainberg, M.A., Antimicrob. Agents Chemother., 35 (1991) 1386.

    Google Scholar 

  146. Chang, C.-N., Doong, S.-L., Zhou, J.H., Beach, J.W., Jeong, L.S., Chu, C.K., Schinazi, R.F., Liotta, D.C. and Cheng, Y.-C., J. Biol. Chem., 267 (1992) 13938.

    Google Scholar 

  147. Coates, J.A.V., Cammack, N., Jenkinson, H.J., Jowett, A.J., Jowell, M.I., Pearson, B.A., Penn, C.R., Rouse, P.L., Viner, K.C. and Cameron, J.M., Antimicrob. Agents Chemother., 36 (1992) 733.

    Google Scholar 

  148. Doong, S.-L., Tsai, C.-H., Schinazi, R.F., Liotta, D.C. and Cheng, Y.-C., Proc. Natl. Acad. Sci. USA, 88 (1991) 8495.

    Google Scholar 

  149. Furman, P.A., Davis, M., Liotta, D.C., Paff, M., Frick, L.W., Nelson, D.J., Dornsife, R.E., Wurster, J.A., Wilson, L.J., Fyfe, J.A., Tuttle, J.V., Miller, W.H., Condreay, L., Averett, D.R., Schinazi, R.F. and Painter, G.R., Antimicrob. Agents Chemother., 36 (1992) 2686.

    Google Scholar 

  150. Hoong, L.K., Strange, L.E., Liotta, D.C., Koszalka, G.W., Burns, C.L. and Schinazi, R.F., J. Org. Chem., 57 (1992) 5563.

    Google Scholar 

  151. Schinazi, R.F., Chu, C.K., Peck, A., McMillan, A., Mathis, R., Cannon, D., Jeong, L.-S., Beach, J.W., Choi, W.-B., Yeola, S. and Liotta, D.C., Antimicrob. Agents Chemother., 36 (1992) 672.

    Google Scholar 

  152. Hart, G.J., Orr, D.C., Penn, C.R., Figueiredo, H.T., Gray, N.M., Boehme, R.E. and Cameron, J.M., Antimicrob. Agents Chemother., 36 (1992) 1688.

    Google Scholar 

  153. Schinazi, R.F., McMillan, A., Cannon, D., Mathis, R., Lloyd, R.M., Peck, A., Sommadossi, J.-P., St. Clair, M., Wilson, J., Painter, G., Choi, W.-B. and Liotta, D.C., Antimicrob. Agents Chemother., 36 (1992) 2423.

    Google Scholar 

  154. Shewach, D.S., Liotta, D.C. and Schinazi, R.F., Biochem. Pharmacol., 45 (1993) 1540.

    Google Scholar 

  155. Sommadossi, J.-P., Schinazi, R.F., Chu, C.K. and Xie, M.-Y., Biochem. Pharmacol., 44 (1992) 1921.

    Google Scholar 

  156. Hizi, A., McGill, C. and Hughes, S.H., Proc. Natl. Acad. Sci. USA, 85 (1988) 1218.

    Google Scholar 

  157. Schinazi, R.F., Eriksson, B.F. and Hughes, S.H., Antimicrob. Agents Chemother., 33 (1989) 115.

    Google Scholar 

  158. Deetz, J.S. and Rozzell, J.D., Trends Biotechnol., 6 (1988) 15.

    Google Scholar 

  159. Zaks, A. and Klibanov, A.M., J. Biol. Chem., 263 (1988) 3194.

    Google Scholar 

  160. Chatis, P.A. and Crumpacker, C.S., Antimicrob. Agents Chemother., 36 (1992) 1589.

    Google Scholar 

  161. Muratore, O., Varnier, O.E., Raffanti, S.P. and Schito, G.C., Eur. J. Clin. Microbiol., 3 (1984) 447.

    Google Scholar 

  162. Larder, B.A., Darby, G. and Richman, D.D., Science, 243 (1989) 1731.

    PubMed  Google Scholar 

  163. Emini, E.A., Schleif, W.A., Byrnes, V.W., Rhodes, A., Titus, D.L., Waterbury, J.A., Quintero, J.C., Gotlib, L., Schneider, C.L., Uncapher, C., Laskin, O.L., Massari, F.E., Kappes, J.C., Shaw, G.M. and Saag, M.S., N. Engl. J. Med., submitted.

  164. Safrin, S., J. Acq. Imm. Defic. Syndr., 5 (1992) S29.

    Google Scholar 

  165. Larder, B.A. and Kemp, S.D., Science, 246 (1989) 1155.

    PubMed  Google Scholar 

  166. Larder, B.A., Kemp, S.D. and Purifoy, J.M., Proc. Natl. Acad. Sci. USA, 86 (1989) 4803.

    Google Scholar 

  167. Larder, B.A., O'Sullivan, E., Kemp, S.D., Ramautarsing, C., Lange, J.M.A., Goudsmit, J. and Boucher, C.A.B., J. Acq. Imm. Defic. Syndr., 4 (1991) 342.

    Google Scholar 

  168. Zimmermann, F., Biesert, L., von Briesen, H., Wegner, R., Helm, E.B., Staszewski, S. and Rübsamen-Waigmann, H., IVth International Conference on AIDS, Stockholm 1988 [Abstr. 3656].

  169. Marx, J.L., Science, 243 (1989) 1551.

    Google Scholar 

  170. Land, S., Treloar, G., McPhee, D., Birch, C., Doherty, R., Cooper, D. and Gust, I., J. Infect. Dis., 161 (1990) 326.

    Google Scholar 

  171. Boucher, C.A.B., Tersmette, M., Lange, J.M.A., Kellam, P., de Goede, R.E.Y., Mulder, J.W., Darby, G., Goudsmit, J. and Larder, B.A., Lancet, 336 (1990) 585.

    PubMed  Google Scholar 

  172. Rooke, R., Tremblay, M., Soudeyns, H., DeStephano, L., Yao, X., Fanning, M., Montaner, J.S.G., O'Shaughnessy, M., Gelmon, K., Tsoukas, C., Gill, J., Ruedy, J., Wainberg, M.A. and Group, C.Z.M.-C.S., AIDS, 3 (1989) 411.

    PubMed  Google Scholar 

  173. D'Aquila, R.T., Videler, J.A., Bechtel, L.B., Johnson, V.A., Merrill, D.P., Eron, J., Kaplan, J.C. and Hirsch, M.S., J. Acq. Imm. Defic. Syndr., 4 (1991) 346.

    Google Scholar 

  174. Gingeras, T.R., Propandovich, P., Latimer, T., Richman, D., Guatelli, J. and Barringer, K., J. Acq. Imm. Defic. Syndr., 4 (1991) 349.

    Google Scholar 

  175. Fitzgibbon, J.E., Howell, R.M., Schwartzer, T.A., Gocke, D.J. and Dubin, D.T., AIDS Res. Hum. Retroviruses, 7 (1991) 265.

    Google Scholar 

  176. Mayers, D., McCutchan, F.E., Sanders-Buell, E., Merritt, L., Fowler, A.F., Ruiz, N.M. and Burke, D.S., J. Acq. Imm. Defic. Syndr., 4 (1991) 343.

    Google Scholar 

  177. Lopez-Galindez, C., Rojas, J., Najera, R., Richman, D. and Perucho, M., J. Acq. Imm. Defic. Syndr., 4 (1991) 343.

    Google Scholar 

  178. Richman, D.D., Grimes, J.M. and Lagakos, S.W., J. Acq. Imm. Defic., Syndr., 3 (1990) 743.

    Google Scholar 

  179. Boucher, C.A.B., O'Sullivan, E., Mulder, J.W., Ramautarsing, C., Kellam, P., Darby, G., Lange, J.M.A., Goudsmit, J. and Larder, B.A., J. Infect. Dis., 165 (1992) 105.

    Google Scholar 

  180. Richman, D.D., Rev. Infect. Dis., 12 (1990) S507.

  181. Richman, D.D., Am. J. Med., 88, suppl. 5B (1990) 8S.

  182. Rooke, R., Parniak, M.A., Tremblay, M., Soudeyns, H., Li, X., Gao, Q., Yao, X.-J. and Wainberg, M.A., Antimicrob. Agents Chemother., 35 (1991) 988.

    Google Scholar 

  183. Larder, B.A., Coates, K.E. and Kemp, S.D., J. Virol., 65 (1991) 5232.

    Google Scholar 

  184. St. Clair, M.H., Martin, J.L., Tudor-Williams, T.G., Bach, M.C. and Furman, P.A., J. Acq. Imm. Defic. Syndr., 4 (1991) 345.

    Google Scholar 

  185. Japour, A.J., Chatis, P.A., Eigenrauch, H.A. and Crumpacker, C.S., Proc. Natl. Acad. Sci. USA, 88 (1991) 3092.

    Google Scholar 

  186. Shirasaka, T., Yarchoan, R., O'Brien, M.C., Husson, R.N., Anderson, B.D., Kojima, E., Shimada, T., Broder, S. and Mitsuya, H., Proc. Natl. Acad. Sci. USA, 90 (1993) 562.

    Google Scholar 

  187. Howell, R.M., Fitzgibbon, J.E., Haberzettl, C., Sperber, S.J., Gocke, D. and Dubin, D.T., 31st Conference on Antimicrobial Agents and Chemotherapy, (1991) 323.

  188. St. Clair, M.H., Martin, J.L., Tudor-Williams, G., Bach, M.C., Vavro, C.L., King, D.M., Kellam, P., Kemp, S.D. and Larder, B.A., Science, 253 (1991) 1557.

    Google Scholar 

  189. Boucher, C., Larder, B., Tijnagel, J., O'Sullivan, E., Lange, J. and Goudsmit, J., J. Acq. Imm. Defic. Syndr., 4 (1991) 346.

    Google Scholar 

  190. Wainberg, M.A., Gu, Z., Gao, Q., Arts, E., Geleziunas, R., Bour, S., Beaulieu, R., Tsoukas, C., Singer, J. and Montaner, J., J. Acq. Imm.Defic. Syndr., 6 (Suppl. 1) (1993) S36.

  191. Larder, B.A., Antimicrob. Agents Chemother., 36 (1992) 2664.

    Google Scholar 

  192. Fitzgibbon, J., Howell, R., Haberzettl, C., Sperber, S., Gocke, D. and Dubin, D., Antimicrob. Agents Chem., 36 (1992) 153.

    Google Scholar 

  193. Zhang, D., Eron, J.J., D'Aquila, R.T. and Hirsch, M.S., 32nd Conference on Antimicrobial Agents and Chemotherapy, Anaheim, (1992) 206.

  194. Prasad, V.R., Lowy, I., de los Santos, T., Chiang, L. and Goff, S.P., Proc. Natl. Acad. Sci. USA, 88 (1991) 11363.

    Google Scholar 

  195. Schinazi, R.F., Lloyd, Jr., R.M., Nguyen, M.-H., Cannon, D.L., McMillan, A., Ilksoy, N., Chu, C.K., Liotta, D.C., Bazmi, H.Z. and Mellors, J.W., Antimicrob. Agents Chemother., 37 (1993) 875.

    Google Scholar 

  196. Remington, K.M., Chesebro, B., Wehrly, K., Pedersen, N.C. and North, T.W., J. Virol., 65 (1991) 308.

    Google Scholar 

  197. Johnson, V.A., Merrill, D.P., Videler, J.A., Chou, T.-C., Byington, R.E., Kaplan, J.C., D'Aguila, R.T. and Hirsch, M.S., J. Acq. Imm. Defic. Syndr., 4 (1991) 354.

    Google Scholar 

  198. Schinazi, R.F., Del Bene, V., Scott, R.T. and Dudley, J.B., J. Antimicrob. Chemother., 18 (1986) 127.

    Google Scholar 

  199. Chou, T. and Talalay, P., Adv. Enzyme. Regul., 22 (1984) 27.

    Google Scholar 

  200. Prichard, M.N. and Shipman, Jr., C., Antiviral Res., 14 (1990) 181.

    Google Scholar 

  201. Weinstein, J., Bunow, B., Weislow, O., Schinazi, R., Wahl, S., Wahl, L. and Szebeni, J., Ann. NY Acad. Sci., 616 (1990) 367.

    Google Scholar 

  202. Bunow, B. and Weinstein, J., Ann. NY Acad. Sci., 616 (1990) 490.

    Google Scholar 

  203. Belen'kii, M.S. and Schinazi, R.F., Antiviral Res., submitted.

  204. Vogt, M., Hartshorn, K.L., Furman, P.A., Chou, T., Fyfe, J.A., Coleman, L.A., Crumpacker, C., Schooley, R.T. and Hirsch, M.S., Science, 235 (1987) 1376.

    Google Scholar 

  205. Balzarini, J., Naesens, L., Robins, M.J. and DeClercq, E., J. Acq. Imm. Defic. Syndr., 3 (1990) 1140.

    Google Scholar 

  206. Balzarini, J., Lee, C.-K., Schols, D. and DeClercq, E., Biochem. Biophys. Res. Commun., 178 (1991) 563.

    Google Scholar 

  207. DeClercq, E., Lancet, 338 (1991) 450.

    Google Scholar 

  208. Eriksson, B.F.H. and Schinazi, R.F., Antimicrob. Agents Chemother., 33 (1989) 778.

    Google Scholar 

  209. Boyer, P.L., Ferris, A.L. and Hughes, S.H., J. Virol., 66 (1992) 1031.

    Google Scholar 

  210. Chow, Y.K., Hirsch, M.S., Merrill, D.P., Bechtel, L.J., Eron, J.J., Kaplan, J.C. and D'Aquila, R.T., Nature, 361 (1993) 650.

    Google Scholar 

  211. Davies, J.F., Hostomska, Z., Hostomsky, Z., Jordan, S.R. and Matthews, D.A., Science, 252 (1991) 88.

    Google Scholar 

  212. Jacobo-Molina, A. and Arnold, E., Biochemistry, 30 (1991) 6351.

    Google Scholar 

  213. Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A. and Steitz, T.A., Science, 256 (1992) 1783.

    Google Scholar 

  214. Amato, I., Science, 256 (1992) 964.

    Google Scholar 

  215. Stinson, S.C., Chem. Eng. News, (1992) 46.

  216. Drysdale, C.M. and Pavlakis, G.N., J. Virol., 65 (1991) 3044.

    Google Scholar 

  217. Langhoff, E. and Haseltine, W.A., J. Invest. Dermatol., 99 (1992) 89s.

    Google Scholar 

  218. Pomerantz, R.J., Seshamma, T. and Trone, D., J. Virol., 66 (1992) 1809.

    Google Scholar 

  219. Vogel, J., Cepeda, M., Tschachler, E., Napolitano, L.A. and Jay, G., J. Virol., 66 (1992) 1.

    Google Scholar 

  220. Ono, K., Ogasawara, M., Ohashi, A., Matsukage, A., Takahashi, T., Nakayama, C. and Saneyoshi, M., Biochemistry, 21 (1982) 1019.

    Google Scholar 

  221. Ono, K., Nakane, H., Herdewijn, P., Balzarini, J. and DeClercq, E., Mol. Pharmacol., 35 (1989) 578.

    Google Scholar 

  222. Matthes, E., Lehmann, C., Von Janta-Lipinski, M. and Scholz, D., Biochem. Biophys. Res. Commun., 165 (1989) 488.

    Google Scholar 

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  1. Veterans Affairs Medical Center, 30033, Decatur, Georgia

    Raymond F. Schinazi

  2. Department of Pediatrics, Laboratory of Biochemical Pharmacology, and Emory University School of Medicine, 30322, Atlanta, GA, USA

    Raymond F. Schinazi

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Schinazi, R.F. Competitive inhibitors of human immunodeficiency virus reverse transcriptase. Perspectives in Drug Discovery and Design 1, 151–180 (1993). https://doi.org/10.1007/BF02171660

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