Cyclic saligenyl phosphotriesters of 2',3'-dideoxy-2',3'-didehydrothymidine (d4T) - A new pro-nucleotide approach

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 2, 1997, Pages 99-104

  Meier, Chris ^a   Lorey, Martina ^a   De Clercq, E ^b   Balzarini, Jan ^b  

^a GOETHE UNIVERSITY   (Germany)

^b REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; NUCLEOSIDE ANALOG; STAVUDINE; STAVUDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; DRUG ACTIVITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; REACTION ANALYSIS;

EID: 0031013734     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(96)00597-5     Document Type: Article

References (24)

1. A preliminary account of this work was presented at the 9th International Conference on Antiviral Research, Fukushima, Japan, May 19-24, 1996; Meier, C.; Lorey, M.; E. De Clercq, Balzarini, J.; Antiviral Res. 1996, 28, A29.
2. A preliminary account of this work was presented at the 9th International Conference on Antiviral Research, Fukushima, Japan, May 19-24, 1996; Meier, C.; Lorey, M.; E. De Clercq, Balzarini, J.; Antiviral Res. 1996, 28, A29.
3. Balzarini, J.; Kang, G.-J.; Dalal, M.; Herdewijn, P.; De Clercq, E.; Broder, S.; Johns, D.G.; Mol. Pharmacol. 1987, 32, 162.
4. Mansuri, M.M.; Hitchcock, M.J.M.; Buroker, R.A.; Bregman, C.L.; Ghazzouli, I.; Desiderio, J.V.; Starrett Jr, J.E.; Sterzycki, R.Z.; J.-P.; Martin, J.C.; Antimicrob. Agents Chemother. 1990, 34, 637.
5. Balzarini, J.; Herdewijn, P.; De Clercq, E.; J. Biol. Chem. 1989, 264, 6127.
6. Jones, R.J.; Bischofberger, N.; Antiviral Res. 1995, 27, 1 and cited literature.
7. Other phosphotriester prodrugs of d4TMP, which should be cleaved by non-specific chemical hydrolysis (Sergheraert, C.; Pierlot, C.; Tartar, A.; Henin, Y.; Lemaitre, M.; J. Med. Chem. 1993, 36, 826) or enzymatic hydrolysis (a. Girardet, J.-L.; Perigaud, C.; Aubertin, A.-M.; Gosselin, G.; Kirn, A.; Imbach, J.-L.; Bioorg. Med. Chem. Lett. 1995, 5, 2981,
8. Other phosphotriester prodrugs of d4TMP, which should be cleaved by non-specific chemical hydrolysis (Sergheraert, C.; Pierlot, C.; Tartar, A.; Henin, Y.; Lemaitre, M.; J. Med. Chem. 1993, 36, 826) or enzymatic hydrolysis (a. Girardet, J.-L.; Perigaud, C.; Aubertin, A.-M.; Gosselin, G.; Kirn, A.; Imbach, J.-L.; Bioorg. Med. Chem. Lett. 1995, 5, 2981,
9. b. McGuigan, C.; Sheeka, H.M.; Mahmood, N.; Hay, A.; Bioorg. Med. Chem. Lett. 1993, 3, 1203,
10. c. McGuigan, C.; Cahard, D.; Sheeka, H.M.; De Clercq, E.; Balzarini, J. Med. Chem. 1996, 39, 1748,
11. d. McGuigan, C.; Cahard, D.; Sheeka, H.M.; De Clercq, E.; Balzarini, Bioorg. Med. Chem. Lett. 1996, 6, 1183) have been reported recently.
12. Meier, C.; Angew. Chem. 1996, 108, 77; Angew. Chem. Int. Ed. Engl. 1996, 35, 70.
13. Meier, C.; Angew. Chem. 1996, 108, 77; Angew. Chem. Int. Ed. Engl. 1996, 35, 70.
14. Farrow, S.N.; Jones, A.S.; Kumar, A.; Walker, R.T.; Balzarini, J.; De Clercq, E.; J. Med. Chem. 1990, 33, 1400.
15. Meier, C.; Habel, L.; Balzarini, J.; De Clercq, E.; Liebigs Ann. 1995, 2203; Habel, L.; Diploma-thesis, University of Frankfurt, 1994.
16. Meier, C.; Habel, L.; Balzarini, J.; De Clercq, E.; Liebigs Ann. 1995, 2203; Habel, L.; Diploma-thesis, University of Frankfurt, 1994.
17. Meier, C. unpublished results; it should be mentioned that these compounds may be substrates for cellular phosphodiesterases but then the question of selectivity arises.
18. Thomson, W.; Nicholls, D.; Irwin, W.J.; Al-Mushadani, J.S.; Freeman, S.; Karpas, A.; Petrik, J.; Mahmood, N.; Hay, A.J.; J. Chem. Soc. Perkin Trans, 1 1993, 1239.
19. Wissner, A.; Carroll, M.L.; J. Med. Chem. 1992, 35, 1650.
20. d4T 1 was synthesized according to the procedure published by: Horwitz, J.P.; Chua, J.; DaRooge, M.A.; Noel, M.; Klundt, I.L.; J. Org. Chem. 1966, 31, 205; taking account of the notes of: Mansuri, M.M.; Starrett Jr, J.E.; Ghazzouli, I.; Hitchcock, M.J.M.; Sterzycki, R.Z.; Brankovan, V.; Lin, T.-S.; August, E.M.; Prusoff, W.H.; Sommadossi, J.-P.; Martin, J.C.; J. Med. Chem. 1989, 32, 461.
21. d4T 1 was synthesized according to the procedure published by: Horwitz, J.P.; Chua, J.; DaRooge, M.A.; Noel, M.; Klundt, I.L.; J. Org. Chem. 1966, 31, 205; taking account of the notes of: Mansuri, M.M.; Starrett Jr, J.E.; Ghazzouli, I.; Hitchcock, M.J.M.; Sterzycki, R.Z.; Brankovan, V.; Lin, T.-S.; August, E.M.; Prusoff, W.H.; Sommadossi, J.-P.; Martin, J.C.; J. Med. Chem. 1989, 32, 461.
22. 2; σ = 0.81; -9.40/-9.64 ppm); 3b (Cl; σ = 0.24; -8.59/8.66 ppm); 3c (H; σ = 0.0; -8.13/-8.15 ppm); 3d (Me; σ = -0.14; -8.04/-8.11).
23. Balzarini, J.; Cools, J.M.; De Clercq, E.; Biochem. Biophys. Res. Commun. 1989, 158, 413.
24. Further hydrolysis studies in culture medium, in plasma and in cell extracts are in progress.