Synthesis of fluorinated phosphonoacetate derivatives of carbocyclic nucleoside monophosphonates and activity as inhibitors of HIV reverse transcriptase

Abstract

The syntheses of compounds 8–10 are described; the compounds showed some activity as inhibitors of HIV reverse transcriptase (IC₅₀ ⩾ 365 µM).

References

1. (a) E. De Clercq, J. Med. Chem., 1995, 38, 2491; (b) H. Mitsuya, K. J. Weinhold, P. A. Furman, M. H. St. Clair, S. N. Lehrman, R. C. Gallo, D. Bolognesi, D. W. Barry and S. Broder, Proc. Natl. Acad. Sci. USA., 1985, 82, 7096.
2. (a) E. J. De Clercq, J. Med. Chem., 1986, 29, 1561; (b) C. Kim, V. Marquez, S. Broder, H. Mitsuya and J. Driscoll, J. Med. Chem., 1987, 30, 867; (c) R. Vince and M. Hua, J. Med. Chem., 1990, 33, 17; (d) J. Balzarini, E. De Clercq, H. Baumgartner, M. Bodenteich and H. Griengl, Mol. Pharmacol., 1990, 37, 395.
3. (a) S. M. Daluge, S. S. Good, M. B. Faletto, W. H. Miller, M. H. St. Clair, L. R. Boone, M. Tisdale, N. R. Parry, J. E. Reardon, R. E. Durnsife, D. R. Averett and T. A. Krenitsky, AIDS, 1997, 41, 1082; (b) R. H. Foster and D. Faulds, Drugs, 1998, 55, 729.
4. V. Merlo, S. M. Roberts, R. Storer and R. Bethell, J. Chem. Soc., Perkin Trans. 1, 1994, 1477.
5. C. J. Hamilton, S. M. Roberts and A. Shipitsin, Chem. Commun., 1998, 1087.
6. T. Rozovskaya, A. Mischenko, N. Tarusova, M. Kukhanova, A. Krayevsky and R. Bibilashvilli, Mol. Biol., 1993, 27, 649.
7. (a) B. Eriksson, A. Larsson, E. Helgstrand, N.-G. Johanson and B. Öberg, Biochim. Biophys. Acta, 1980, 607, 53; (b) B. Eriksson, B. Öberg and B. Wahren, ibid, 1982, 696, 115; (c) S. S. Leinbach, J. M. Reno, L. F. Lee, A. F. Isbell and J. A. Boezi, Biochemistry, 1976, 15, 426; (d) C. Crumpacker, Am. J. Med., 1992, 92(suppl. 2A), 2A-3S and references therein.
8. For mechanistic studies on the role of phosphonoformic and phosphonoacetic acid as irreversible non-competitive inhibitors of DNA polymerases see: (a) B. A. Larder, D. J. M. Purifoy, K. L. Powell and G. Darby, Nature, 1987, 327, 716; (b) S. Leinbach, J. Reno, L. Lee, A. Isbell and J. Boezi, Biochemistry, 1976, 15, 426; (c) P. Chrisp and S. Clissod, Drugs, 1991, 41, 102.
9. G. M. Blackburn, D. Brown and S. Martin, J. Chem. Res. (S), 1985, 92.
10. D. Philion and S. Andrew, Tetrahedron Lett., 1986, 27, 1477.
11. G. M. Blackburn, D. Brown, S. Martin and M. Parrat, J. Chem. Soc., Perkin Trans. 1, 1987, 181.
12. F. Davis, W. Han and C. Murphy, J. Org. Chem., 1995, 60, 4730.
13. F. Davis and W. Han, Tetrahedron Lett., 1991, 32, 1631.
14. E. Differding, R. Duthaler, A. Krieger, G. Rüegg and C. Schmit, Synlett, 1991, 395.
15. G. Sankar Lal, J. Org. Chem., 1993, 58, 2791.
16. G. Sankar Lal, G. Pez and R. Syvet, Chem. Rev., 1996, 96, 1737.
17. J. Moffatt and H. Khorana, J. Am. Chem. Soc., 1961, 83, 649.
18. A. Arzumanov, D. Semizarov, L. Victorova, N. Dyatkina and A. Krayevsky, J. Biol. Chem., 1996, 271, 24389.
19. D. Burton and L. Sprague, J. Org. Chem., 1988, 53, 1523.
20. P. Kedar, J. Abbotts, T. Kovacs, K. Lesiak, P. Torrence and S. Wilson, Biochemistry, 1990, 29, 3603.