Pyrroloindole analogues of ellipticine. The synthesis and DNA intercalative properties of 5,10-dihydro-5,10-dimethyl-2,5,10-triazadibenzo[a,e]pentalene

Tetrahedron

Volumn 53, Issue 2, 1997, Pages 479-486

  Jones, R Alan ^a   Pastor, Joachim ^a   Siro, Jorge ^b   Voro, Tevita N ^a  

^a UNIVERSITY OF EAST ANGLIA   (United Kingdom)

^b UNIVERSITY OF ALCALÁ   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

5,10 DIHYDRO 2,5,10 TRIMETHYL 2,5,10 TRIAZADIBENZO[A,E]PENTALENIUM IODIDE; 5,10 DIHYDRO 5,10 DIMETHYL 2,5,10 TRIAZADIBENZO[A,E]PENTALENE; 9 HYDROXYELLIPTICINE; 9 METHOXYELLIPTICINE; ELLIPTICINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DNA BINDING; DRUG SYNTHESIS; PKA; PRIORITY JOURNAL;

EID: 0031021768     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4020(96)00994-5     Document Type: Article

References (42)

1. For reviews, see, for example, Sainsbury, M. Synthesis, 1977, 437-448; Hewlins, M.J.E.; Oliveira-Campos, A-M.; Shannon, P.V.R. ibid., 1984, 289-302; Gribble, G.W. and Saulnier, M.G Heterocycles, 1985, 23, 1277-1315; Dormay, J-R.; Heymes, A. Tetrahedron, 1993, 49, 2885-2914; 1993, 49, 2915-2938 .
2. For reviews, see, for example, Sainsbury, M. Synthesis, 1977, 437-448; Hewlins, M.J.E.; Oliveira-Campos, A-M.; Shannon, P.V.R. ibid., 1984, 289-302; Gribble, G.W. and Saulnier, M.G Heterocycles, 1985, 23, 1277-1315; Dormay, J-R.; Heymes, A. Tetrahedron, 1993, 49, 2885-2914; 1993, 49, 2915-2938 .
3. For reviews, see, for example, Sainsbury, M. Synthesis, 1977, 437-448; Hewlins, M.J.E.; Oliveira-Campos, A-M.; Shannon, P.V.R. ibid., 1984, 289-302; Gribble, G.W. and Saulnier, M.G Heterocycles, 1985, 23, 1277-1315; Dormay, J-R.; Heymes, A. Tetrahedron, 1993, 49, 2885-2914; 1993, 49, 2915-2938 .
4. For reviews, see, for example, Sainsbury, M. Synthesis, 1977, 437-448; Hewlins, M.J.E.; Oliveira-Campos, A-M.; Shannon, P.V.R. ibid., 1984, 289-302; Gribble, G.W. and Saulnier, M.G Heterocycles, 1985, 23, 1277-1315; Dormay, J-R.; Heymes, A. Tetrahedron, 1993, 49, 2885-2914; 1993, 49, 2915-2938 .
5. For reviews, see, for example, Sainsbury, M. Synthesis, 1977, 437-448; Hewlins, M.J.E.; Oliveira-Campos, A-M.; Shannon, P.V.R. ibid., 1984, 289-302; Gribble, G.W. and Saulnier, M.G Heterocycles, 1985, 23, 1277-1315; Dormay, J-R.; Heymes, A. Tetrahedron, 1993, 49, 2885-2914; 1993, 49, 2915-2938 .
6. A computer-analysed programme indicates that there are at least 253 conceivable routes to form the four-ring ellipticine system. Barone, R.; Chanon, M. Heterocycles, 1981, 16, 1357-136 5.
7. see, for example, Dalton, L.K.; Demerac, S.; Elmes, B.C.; Loder, J.W.; Swan, J.M.; Teitei, T. Aust. J. Chem., 1967, 20, 2715-2727; Mathé, G.; Hayat, M.; De Vassal, F.; Schwarzenberg, L.; Schneider, M.; Schumberger, J.R.; Jasmin, C.; Rosenfeld, C. Rev. Eur. Etud. Clin. Biol., 1970, 5, 541-545; Guthrie, R.W.; Brossi, A.; Mennona, F.A.; Mullin, J.G.; Kierstead, R.W.; Grunberg, E. J. Med. Chem., 1975, 18, 755-760; Le Pecq, J.B., Gosse, G., Dat-Xuong, N.; Cros, S.; Paoletti, C. Cancer Res., 1976, 36, 3067-3076 and references cited therein; Werbel, L.M.; Angelo, M.; Fry, D.W.; Worth, D.F. J. Med. Chem., 1986, 29, 1321-1322; Auclair, C.; Meunier, B.; Paoletti, C. Biochem. Pharmacol., 1983, 32, 3883-3886; Archer, S.; Ross, B.S.; Pica-Mattoccia, L.; Cioli, D. J. Med. Chem., 1987, 30, 1204-1210; Kattan, J; Durand, M; Droz, J.P.; Mahjoubi, M.; Marino, J.P.; Azab, M. Ann. J. Clin. Oncol., 1994, 17, 242-245; Jurayj, Haugwitz, R.D.; Varma, R.K.; Paull, K.D.; Barrett, J.F.; Cushman, M. J. Med. Chem., 1994, 37, 2190-2197 and references cited therein.
8. see, for example, Dalton, L.K.; Demerac, S.; Elmes, B.C.; Loder, J.W.; Swan, J.M.; Teitei, T. Aust. J. Chem., 1967, 20, 2715-2727; Mathé, G.; Hayat, M.; De Vassal, F.; Schwarzenberg, L.; Schneider, M.; Schumberger, J.R.; Jasmin, C.; Rosenfeld, C. Rev. Eur. Etud. Clin. Biol., 1970, 5, 541-545; Guthrie, R.W.; Brossi, A.; Mennona, F.A.; Mullin, J.G.; Kierstead, R.W.; Grunberg, E. J. Med. Chem., 1975, 18, 755-760; Le Pecq, J.B., Gosse, G., Dat-Xuong, N.; Cros, S.; Paoletti, C. Cancer Res., 1976, 36, 3067-3076 and references cited therein; Werbel, L.M.; Angelo, M.; Fry, D.W.; Worth, D.F. J. Med. Chem., 1986, 29, 1321-1322; Auclair, C.; Meunier, B.; Paoletti, C. Biochem. Pharmacol., 1983, 32, 3883-3886; Archer, S.; Ross, B.S.; Pica-Mattoccia, L.; Cioli, D. J. Med. Chem., 1987, 30, 1204-1210; Kattan, J; Durand, M; Droz, J.P.; Mahjoubi, M.; Marino, J.P.; Azab, M. Ann. J. Clin. Oncol., 1994, 17, 242-245; Jurayj, Haugwitz, R.D.; Varma, R.K.; Paull, K.D.; Barrett, J.F.; Cushman, M. J. Med. Chem., 1994, 37, 2190-2197 and references cited therein.
9. see, for example, Dalton, L.K.; Demerac, S.; Elmes, B.C.; Loder, J.W.; Swan, J.M.; Teitei, T. Aust. J. Chem., 1967, 20, 2715-2727; Mathé, G.; Hayat, M.; De Vassal, F.; Schwarzenberg, L.; Schneider, M.; Schumberger, J.R.; Jasmin, C.; Rosenfeld, C. Rev. Eur. Etud. Clin. Biol., 1970, 5, 541-545; Guthrie, R.W.; Brossi, A.; Mennona, F.A.; Mullin, J.G.; Kierstead, R.W.; Grunberg, E. J. Med. Chem., 1975, 18, 755-760; Le Pecq, J.B., Gosse, G., Dat-Xuong, N.; Cros, S.; Paoletti, C. Cancer Res., 1976, 36, 3067-3076 and references cited therein; Werbel, L.M.; Angelo, M.; Fry, D.W.; Worth, D.F. J. Med. Chem., 1986, 29, 1321-1322; Auclair, C.; Meunier, B.; Paoletti, C. Biochem. Pharmacol., 1983, 32, 3883-3886; Archer, S.; Ross, B.S.; Pica-Mattoccia, L.; Cioli, D. J. Med. Chem., 1987, 30, 1204-1210; Kattan, J; Durand, M; Droz, J.P.; Mahjoubi, M.; Marino, J.P.; Azab, M. Ann. J. Clin. Oncol., 1994, 17, 242-245; Jurayj, Haugwitz, R.D.; Varma, R.K.; Paull, K.D.; Barrett, J.F.; Cushman, M. J. Med. Chem., 1994, 37, 2190-2197 and references cited therein.
10. see, for example, Dalton, L.K.; Demerac, S.; Elmes, B.C.; Loder, J.W.; Swan, J.M.; Teitei, T. Aust. J. Chem., 1967, 20, 2715-2727; Mathé, G.; Hayat, M.; De Vassal, F.; Schwarzenberg, L.; Schneider, M.; Schumberger, J.R.; Jasmin, C.; Rosenfeld, C. Rev. Eur. Etud. Clin. Biol., 1970, 5, 541-545; Guthrie, R.W.; Brossi, A.; Mennona, F.A.; Mullin, J.G.; Kierstead, R.W.; Grunberg, E. J. Med. Chem., 1975, 18, 755-760; Le Pecq, J.B., Gosse, G., Dat-Xuong, N.; Cros, S.; Paoletti, C. Cancer Res., 1976, 36, 3067-3076 and references cited therein; Werbel, L.M.; Angelo, M.; Fry, D.W.; Worth, D.F. J. Med. Chem., 1986, 29, 1321-1322; Auclair, C.; Meunier, B.; Paoletti, C. Biochem. Pharmacol., 1983, 32, 3883-3886; Archer, S.; Ross, B.S.; Pica-Mattoccia, L.; Cioli, D. J. Med. Chem., 1987, 30, 1204-1210; Kattan, J; Durand, M; Droz, J.P.; Mahjoubi, M.; Marino, J.P.; Azab, M. Ann. J. Clin. Oncol., 1994, 17, 242-245; Jurayj, Haugwitz, R.D.; Varma, R.K.; Paull, K.D.; Barrett, J.F.; Cushman, M. J. Med. Chem., 1994, 37, 2190-2197 and references cited therein.
11. see, for example, Dalton, L.K.; Demerac, S.; Elmes, B.C.; Loder, J.W.; Swan, J.M.; Teitei, T. Aust. J. Chem., 1967, 20, 2715-2727; Mathé, G.; Hayat, M.; De Vassal, F.; Schwarzenberg, L.; Schneider, M.; Schumberger, J.R.; Jasmin, C.; Rosenfeld, C. Rev. Eur. Etud. Clin. Biol., 1970, 5, 541-545; Guthrie, R.W.; Brossi, A.; Mennona, F.A.; Mullin, J.G.; Kierstead, R.W.; Grunberg, E. J. Med. Chem., 1975, 18, 755-760; Le Pecq, J.B., Gosse, G., Dat-Xuong, N.; Cros, S.; Paoletti, C. Cancer Res., 1976, 36, 3067-3076 and references cited therein; Werbel, L.M.; Angelo, M.; Fry, D.W.; Worth, D.F. J. Med. Chem., 1986, 29, 1321-1322; Auclair, C.; Meunier, B.; Paoletti, C. Biochem. Pharmacol., 1983, 32, 3883-3886; Archer, S.; Ross, B.S.; Pica-Mattoccia, L.; Cioli, D. J. Med. Chem., 1987, 30, 1204-1210; Kattan, J; Durand, M; Droz, J.P.; Mahjoubi, M.; Marino, J.P.; Azab, M. Ann. J. Clin. Oncol., 1994, 17, 242-245; Jurayj, Haugwitz, R.D.; Varma, R.K.; Paull, K.D.; Barrett, J.F.; Cushman, M. J. Med. Chem., 1994, 37, 2190-2197 and references cited therein.
12. see, for example, Dalton, L.K.; Demerac, S.; Elmes, B.C.; Loder, J.W.; Swan, J.M.; Teitei, T. Aust. J. Chem., 1967, 20, 2715-2727; Mathé, G.; Hayat, M.; De Vassal, F.; Schwarzenberg, L.; Schneider, M.; Schumberger, J.R.; Jasmin, C.; Rosenfeld, C. Rev. Eur. Etud. Clin. Biol., 1970, 5, 541-545; Guthrie, R.W.; Brossi, A.; Mennona, F.A.; Mullin, J.G.; Kierstead, R.W.; Grunberg, E. J. Med. Chem., 1975, 18, 755-760; Le Pecq, J.B., Gosse, G., Dat-Xuong, N.; Cros, S.; Paoletti, C. Cancer Res., 1976, 36, 3067-3076 and references cited therein; Werbel, L.M.; Angelo, M.; Fry, D.W.; Worth, D.F. J. Med. Chem., 1986, 29, 1321-1322; Auclair, C.; Meunier, B.; Paoletti, C. Biochem. Pharmacol., 1983, 32, 3883-3886; Archer, S.; Ross, B.S.; Pica-Mattoccia, L.; Cioli, D. J. Med. Chem., 1987, 30, 1204-1210; Kattan, J; Durand, M; Droz, J.P.; Mahjoubi, M.; Marino, J.P.; Azab, M. Ann. J. Clin. Oncol., 1994, 17, 242-245; Jurayj, Haugwitz, R.D.; Varma, R.K.; Paull, K.D.; Barrett, J.F.; Cushman, M. J. Med. Chem., 1994, 37, 2190-2197 and references cited therein.
13. see, for example, Dalton, L.K.; Demerac, S.; Elmes, B.C.; Loder, J.W.; Swan, J.M.; Teitei, T. Aust. J. Chem., 1967, 20, 2715-2727; Mathé, G.; Hayat, M.; De Vassal, F.; Schwarzenberg, L.; Schneider, M.; Schumberger, J.R.; Jasmin, C.; Rosenfeld, C. Rev. Eur. Etud. Clin. Biol., 1970, 5, 541-545; Guthrie, R.W.; Brossi, A.; Mennona, F.A.; Mullin, J.G.; Kierstead, R.W.; Grunberg, E. J. Med. Chem., 1975, 18, 755-760; Le Pecq, J.B., Gosse, G., Dat-Xuong, N.; Cros, S.; Paoletti, C. Cancer Res., 1976, 36, 3067-3076 and references cited therein; Werbel, L.M.; Angelo, M.; Fry, D.W.; Worth, D.F. J. Med. Chem., 1986, 29, 1321-1322; Auclair, C.; Meunier, B.; Paoletti, C. Biochem. Pharmacol., 1983, 32, 3883-3886; Archer, S.; Ross, B.S.; Pica-Mattoccia, L.; Cioli, D. J. Med. Chem., 1987, 30, 1204-1210; Kattan, J; Durand, M; Droz, J.P.; Mahjoubi, M.; Marino, J.P.; Azab, M. Ann. J. Clin. Oncol., 1994, 17, 242-245; Jurayj, Haugwitz, R.D.; Varma, R.K.; Paull, K.D.; Barrett, J.F.; Cushman, M. J. Med. Chem., 1994, 37, 2190-2197 and references cited therein.
14. see, for example, Dalton, L.K.; Demerac, S.; Elmes, B.C.; Loder, J.W.; Swan, J.M.; Teitei, T. Aust. J. Chem., 1967, 20, 2715-2727; Mathé, G.; Hayat, M.; De Vassal, F.; Schwarzenberg, L.; Schneider, M.; Schumberger, J.R.; Jasmin, C.; Rosenfeld, C. Rev. Eur. Etud. Clin. Biol., 1970, 5, 541-545; Guthrie, R.W.; Brossi, A.; Mennona, F.A.; Mullin, J.G.; Kierstead, R.W.; Grunberg, E. J. Med. Chem., 1975, 18, 755-760; Le Pecq, J.B., Gosse, G., Dat-Xuong, N.; Cros, S.; Paoletti, C. Cancer Res., 1976, 36, 3067-3076 and references cited therein; Werbel, L.M.; Angelo, M.; Fry, D.W.; Worth, D.F. J. Med. Chem., 1986, 29, 1321-1322; Auclair, C.; Meunier, B.; Paoletti, C. Biochem. Pharmacol., 1983, 32, 3883-3886; Archer, S.; Ross, B.S.; Pica-Mattoccia, L.; Cioli, D. J. Med. Chem., 1987, 30, 1204-1210; Kattan, J; Durand, M; Droz, J.P.; Mahjoubi, M.; Marino, J.P.; Azab, M. Ann. J. Clin. Oncol., 1994, 17, 242-245; Jurayj, Haugwitz, R.D.; Varma, R.K.; Paull, K.D.; Barrett, J.F.; Cushman, M. J. Med. Chem., 1994, 37, 2190-2197 and references cited therein.
15. see, for example, Dalton, L.K.; Demerac, S.; Elmes, B.C.; Loder, J.W.; Swan, J.M.; Teitei, T. Aust. J. Chem., 1967, 20, 2715-2727; Mathé, G.; Hayat, M.; De Vassal, F.; Schwarzenberg, L.; Schneider, M.; Schumberger, J.R.; Jasmin, C.; Rosenfeld, C. Rev. Eur. Etud. Clin. Biol., 1970, 5, 541-545; Guthrie, R.W.; Brossi, A.; Mennona, F.A.; Mullin, J.G.; Kierstead, R.W.; Grunberg, E. J. Med. Chem., 1975, 18, 755-760; Le Pecq, J.B., Gosse, G., Dat-Xuong, N.; Cros, S.; Paoletti, C. Cancer Res., 1976, 36, 3067-3076 and references cited therein; Werbel, L.M.; Angelo, M.; Fry, D.W.; Worth, D.F. J. Med. Chem., 1986, 29, 1321-1322; Auclair, C.; Meunier, B.; Paoletti, C. Biochem. Pharmacol., 1983, 32, 3883-3886; Archer, S.; Ross, B.S.; Pica-Mattoccia, L.; Cioli, D. J. Med. Chem., 1987, 30, 1204-1210; Kattan, J; Durand, M; Droz, J.P.; Mahjoubi, M.; Marino, J.P.; Azab, M. Ann. J. Clin. Oncol., 1994, 17, 242-245; Jurayj, Haugwitz, R.D.; Varma, R.K.; Paull, K.D.; Barrett, J.F.; Cushman, M. J. Med. Chem., 1994, 37, 2190-2197 and references cited therein.
16. Le Pecq, J.B.; Dat-Xuong, N.; Gosse, G.; Paoletti, C. Proc. Natl. Acad. Sci. USA, 1974, 71, 5078-5082.
17. see, for example, Delbarre, A.; Roques, B.P.; Le Pecq, J.B.; Lallemand, J.Y.; Dat-Xuong, N. Biophys. Chem., 1976, 4, 275-279; Jain, S.C.; Bhandary, K.K.; Sobell, H.M. J. Mol. Biol., 1979, 135, 813-840; Auclair, C, Voisen, E.; Banoun, H.; Paoletti, C.; Bernadon, J.; Meunier, B.; J. Med. Chem., 1984, 27, 1161-1166; Kuroda, R.; Sainsbury, M. J. Chem. Soc., Perkin Trans. 2, 1984, 1715-1753; Auclair, C.; Dague, B.; Meunier, B.; Paoletti, C. Biochem., 1986, 25, 1240-1245; Monnot, M.; Mauffret, O.; Simon, V.; Lescot, E.; Psaume, B.; Saucier, J-M.; Charra, M.; Belehradek, J.; Fermandjian, S. J. Biol. Chem., 1991, 266, 1820-1829; Froelich-Ammon, S.J.; Patchan, M.W.; Osheroff, N.; Thompson, R.B. J. Biol. Chem., 1995, 270, 14998-156004.
18. see, for example, Delbarre, A.; Roques, B.P.; Le Pecq, J.B.; Lallemand, J.Y.; Dat-Xuong, N. Biophys. Chem., 1976, 4, 275-279; Jain, S.C.; Bhandary, K.K.; Sobell, H.M. J. Mol. Biol., 1979, 135, 813-840; Auclair, C, Voisen, E.; Banoun, H.; Paoletti, C.; Bernadon, J.; Meunier, B.; J. Med. Chem., 1984, 27, 1161-1166; Kuroda, R.; Sainsbury, M. J. Chem. Soc., Perkin Trans. 2, 1984, 1715-1753; Auclair, C.; Dague, B.; Meunier, B.; Paoletti, C. Biochem., 1986, 25, 1240-1245; Monnot, M.; Mauffret, O.; Simon, V.; Lescot, E.; Psaume, B.; Saucier, J-M.; Charra, M.; Belehradek, J.; Fermandjian, S. J. Biol. Chem., 1991, 266, 1820-1829; Froelich-Ammon, S.J.; Patchan, M.W.; Osheroff, N.; Thompson, R.B. J. Biol. Chem., 1995, 270, 14998-156004.
19. see, for example, Delbarre, A.; Roques, B.P.; Le Pecq, J.B.; Lallemand, J.Y.; Dat-Xuong, N. Biophys. Chem., 1976, 4, 275-279; Jain, S.C.; Bhandary, K.K.; Sobell, H.M. J. Mol. Biol., 1979, 135, 813-840; Auclair, C, Voisen, E.; Banoun, H.; Paoletti, C.; Bernadon, J.; Meunier, B.; J. Med. Chem., 1984, 27, 1161-1166; Kuroda, R.; Sainsbury, M. J. Chem. Soc., Perkin Trans. 2, 1984, 1715-1753; Auclair, C.; Dague, B.; Meunier, B.; Paoletti, C. Biochem., 1986, 25, 1240-1245; Monnot, M.; Mauffret, O.; Simon, V.; Lescot, E.; Psaume, B.; Saucier, J-M.; Charra, M.; Belehradek, J.; Fermandjian, S. J. Biol. Chem., 1991, 266, 1820-1829; Froelich-Ammon, S.J.; Patchan, M.W.; Osheroff, N.; Thompson, R.B. J. Biol. Chem., 1995, 270, 14998-156004.
20. see, for example, Delbarre, A.; Roques, B.P.; Le Pecq, J.B.; Lallemand, J.Y.; Dat-Xuong, N. Biophys. Chem., 1976, 4, 275-279; Jain, S.C.; Bhandary, K.K.; Sobell, H.M. J. Mol. Biol., 1979, 135, 813-840; Auclair, C, Voisen, E.; Banoun, H.; Paoletti, C.; Bernadon, J.; Meunier, B.; J. Med. Chem., 1984, 27, 1161-1166; Kuroda, R.; Sainsbury, M. J. Chem. Soc., Perkin Trans. 2, 1984, 1715-1753; Auclair, C.; Dague, B.; Meunier, B.; Paoletti, C. Biochem., 1986, 25, 1240-1245; Monnot, M.; Mauffret, O.; Simon, V.; Lescot, E.; Psaume, B.; Saucier, J-M.; Charra, M.; Belehradek, J.; Fermandjian, S. J. Biol. Chem., 1991, 266, 1820-1829; Froelich-Ammon, S.J.; Patchan, M.W.; Osheroff, N.; Thompson, R.B. J. Biol. Chem., 1995, 270, 14998-156004.
21. see, for example, Delbarre, A.; Roques, B.P.; Le Pecq, J.B.; Lallemand, J.Y.; Dat-Xuong, N. Biophys. Chem., 1976, 4, 275-279; Jain, S.C.; Bhandary, K.K.; Sobell, H.M. J. Mol. Biol., 1979, 135, 813-840; Auclair, C, Voisen, E.; Banoun, H.; Paoletti, C.; Bernadon, J.; Meunier, B.; J. Med. Chem., 1984, 27, 1161-1166; Kuroda, R.; Sainsbury, M. J. Chem. Soc., Perkin Trans. 2, 1984, 1715-1753; Auclair, C.; Dague, B.; Meunier, B.; Paoletti, C. Biochem., 1986, 25, 1240-1245; Monnot, M.; Mauffret, O.; Simon, V.; Lescot, E.; Psaume, B.; Saucier, J-M.; Charra, M.; Belehradek, J.; Fermandjian, S. J. Biol. Chem., 1991, 266, 1820-1829; Froelich-Ammon, S.J.; Patchan, M.W.; Osheroff, N.; Thompson, R.B. J. Biol. Chem., 1995, 270, 14998-156004.
22. see, for example, Delbarre, A.; Roques, B.P.; Le Pecq, J.B.; Lallemand, J.Y.; Dat-Xuong, N. Biophys. Chem., 1976, 4, 275-279; Jain, S.C.; Bhandary, K.K.; Sobell, H.M. J. Mol. Biol., 1979, 135, 813-840; Auclair, C, Voisen, E.; Banoun, H.; Paoletti, C.; Bernadon, J.; Meunier, B.; J. Med. Chem., 1984, 27, 1161-1166; Kuroda, R.; Sainsbury, M. J. Chem. Soc., Perkin Trans. 2, 1984, 1715-1753; Auclair, C.; Dague, B.; Meunier, B.; Paoletti, C. Biochem., 1986, 25, 1240-1245; Monnot, M.; Mauffret, O.; Simon, V.; Lescot, E.; Psaume, B.; Saucier, J-M.; Charra, M.; Belehradek, J.; Fermandjian, S. J. Biol. Chem., 1991, 266, 1820-1829; Froelich-Ammon, S.J.; Patchan, M.W.; Osheroff, N.; Thompson, R.B. J. Biol. Chem., 1995, 270, 14998-156004.
23. see, for example, Delbarre, A.; Roques, B.P.; Le Pecq, J.B.; Lallemand, J.Y.; Dat-Xuong, N. Biophys. Chem., 1976, 4, 275-279; Jain, S.C.; Bhandary, K.K.; Sobell, H.M. J. Mol. Biol., 1979, 135, 813-840; Auclair, C, Voisen, E.; Banoun, H.; Paoletti, C.; Bernadon, J.; Meunier, B.; J. Med. Chem., 1984, 27, 1161-1166; Kuroda, R.; Sainsbury, M. J. Chem. Soc., Perkin Trans. 2, 1984, 1715-1753; Auclair, C.; Dague, B.; Meunier, B.; Paoletti, C. Biochem., 1986, 25, 1240-1245; Monnot, M.; Mauffret, O.; Simon, V.; Lescot, E.; Psaume, B.; Saucier, J-M.; Charra, M.; Belehradek, J.; Fermandjian, S. J. Biol. Chem., 1991, 266, 1820-1829; Froelich-Ammon, S.J.; Patchan, M.W.; Osheroff, N.; Thompson, R.B. J. Biol. Chem., 1995, 270, 14998-156004.
24. see, for example, Le Pecq, J.B.; Paoletti, C. US patent 4310667 (1981), Chem. Abstr., 1982, 96, 181489; Wanner, M.J.; Koome, G.J.; Pandit, U.K. Tetrahedron, 1983, 39, 3673-3681; Auclair, C.; Bernadon, J.E.; Cier, A.; Meunier, G.A.; Meunier, B.; Paoletti, C. Fr Demande FR 2,527,209 (1983), Chem. Abstr., 1984, 100, 156585; Langendoen, A.; Koomen, G.J.; Pandit, U.K. Tetrahedron, 1988, 44, 3627-3631; Honda, T.; Kato, M.; Inoue, M.; Shimamoto, T.; Shima, K.; Nakanishi, T.; Yoshida, T.; Noguchi, T. J. Med. Chem., 1988, 311, 1295-1305.
25. see, for example, Le Pecq, J.B.; Paoletti, C. US patent 4310667 (1981), Chem. Abstr., 1982, 96, 181489; Wanner, M.J.; Koome, G.J.; Pandit, U.K. Tetrahedron, 1983, 39, 3673-3681; Auclair, C.; Bernadon, J.E.; Cier, A.; Meunier, G.A.; Meunier, B.; Paoletti, C. Fr Demande FR 2,527,209 (1983), Chem. Abstr., 1984, 100, 156585; Langendoen, A.; Koomen, G.J.; Pandit, U.K. Tetrahedron, 1988, 44, 3627-3631; Honda, T.; Kato, M.; Inoue, M.; Shimamoto, T.; Shima, K.; Nakanishi, T.; Yoshida, T.; Noguchi, T. J. Med. Chem., 1988, 311, 1295-1305.
26. see, for example, Le Pecq, J.B.; Paoletti, C. US patent 4310667 (1981), Chem. Abstr., 1982, 96, 181489; Wanner, M.J.; Koome, G.J.; Pandit, U.K. Tetrahedron, 1983, 39, 3673-3681; Auclair, C.; Bernadon, J.E.; Cier, A.; Meunier, G.A.; Meunier, B.; Paoletti, C. Fr Demande FR 2,527,209 (1983), Chem. Abstr., 1984, 100, 156585; Langendoen, A.; Koomen, G.J.; Pandit, U.K. Tetrahedron, 1988, 44, 3627-3631; Honda, T.; Kato, M.; Inoue, M.; Shimamoto, T.; Shima, K.; Nakanishi, T.; Yoshida, T.; Noguchi, T. J. Med. Chem., 1988, 311, 1295-1305.
27. see, for example, Le Pecq, J.B.; Paoletti, C. US patent 4310667 (1981), Chem. Abstr., 1982, 96, 181489; Wanner, M.J.; Koome, G.J.; Pandit, U.K. Tetrahedron, 1983, 39, 3673-3681; Auclair, C.; Bernadon, J.E.; Cier, A.; Meunier, G.A.; Meunier, B.; Paoletti, C. Fr Demande FR 2,527,209 (1983), Chem. Abstr., 1984, 100, 156585; Langendoen, A.; Koomen, G.J.; Pandit, U.K. Tetrahedron, 1988, 44, 3627-3631; Honda, T.; Kato, M.; Inoue, M.; Shimamoto, T.; Shima, K.; Nakanishi, T.; Yoshida, T.; Noguchi, T. J. Med. Chem., 1988, 311, 1295-1305.
28. see, for example, Le Pecq, J.B.; Paoletti, C. US patent 4310667 (1981), Chem. Abstr., 1982, 96, 181489; Wanner, M.J.; Koome, G.J.; Pandit, U.K. Tetrahedron, 1983, 39, 3673-3681; Auclair, C.; Bernadon, J.E.; Cier, A.; Meunier, G.A.; Meunier, B.; Paoletti, C. Fr Demande FR 2,527,209 (1983), Chem. Abstr., 1984, 100, 156585; Langendoen, A.; Koomen, G.J.; Pandit, U.K. Tetrahedron, 1988, 44, 3627-3631; Honda, T.; Kato, M.; Inoue, M.; Shimamoto, T.; Shima, K.; Nakanishi, T.; Yoshida, T.; Noguchi, T. J. Med. Chem., 1988, 311, 1295-1305.
29. see, for example, Le Pecq, J.B.; Paoletti, C. US patent 4310667 (1981), Chem. Abstr., 1982, 96, 181489; Wanner, M.J.; Koome, G.J.; Pandit, U.K. Tetrahedron, 1983, 39, 3673-3681; Auclair, C.; Bernadon, J.E.; Cier, A.; Meunier, G.A.; Meunier, B.; Paoletti, C. Fr Demande FR 2,527,209 (1983), Chem. Abstr., 1984, 100, 156585; Langendoen, A.; Koomen, G.J.; Pandit, U.K. Tetrahedron, 1988, 44, 3627-3631; Honda, T.; Kato, M.; Inoue, M.; Shimamoto, T.; Shima, K.; Nakanishi, T.; Yoshida, T.; Noguchi, T. J. Med. Chem., 1988, 311, 1295-1305.
30. see, for example, Le Pecq, J.B.; Paoletti, C. US patent 4310667 (1981), Chem. Abstr., 1982, 96, 181489; Wanner, M.J.; Koome, G.J.; Pandit, U.K. Tetrahedron, 1983, 39, 3673-3681; Auclair, C.; Bernadon, J.E.; Cier, A.; Meunier, G.A.; Meunier, B.; Paoletti, C. Fr Demande FR 2,527,209 (1983), Chem. Abstr., 1984, 100, 156585; Langendoen, A.; Koomen, G.J.; Pandit, U.K. Tetrahedron, 1988, 44, 3627-3631; Honda, T.; Kato, M.; Inoue, M.; Shimamoto, T.; Shima, K.; Nakanishi, T.; Yoshida, T.; Noguchi, T. J. Med. Chem., 1988, 311, 1295-1305.
31. see, for example, Rivalle, C.; Ducrocq, C.; Bisagni, E. J. Chem. Soc., Perkin Trans. 1, 1979, 138-141; Ducrocq, C.; Bisagni, E.; Rivalle, C.; Lhoste, J-M. ibid., 1979, 142-145; Moustacchi, E.; Favaudon, V.; Bisagni, E. Cancer Res., 1983, 43, 3700-3706; Fontaine-Aupart, M.P.; Laguitton-Pasquier, H.; Pansu, R.; Brian, L.; Renault, E.; Marden, M.C.; Rivalle, C.; Bisagni, E. J. Chem.Soc., Perkin Trans. 2, 1996, 1767-1774.
32. see, for example, Rivalle, C.; Ducrocq, C.; Bisagni, E. J. Chem. Soc., Perkin Trans. 1, 1979, 138-141; Ducrocq, C.; Bisagni, E.; Rivalle, C.; Lhoste, J-M. ibid., 1979, 142-145; Moustacchi, E.; Favaudon, V.; Bisagni, E. Cancer Res., 1983, 43, 3700-3706; Fontaine-Aupart, M.P.; Laguitton-Pasquier, H.; Pansu, R.; Brian, L.; Renault, E.; Marden, M.C.; Rivalle, C.; Bisagni, E. J. Chem.Soc., Perkin Trans. 2, 1996, 1767-1774.
33. see, for example, Rivalle, C.; Ducrocq, C.; Bisagni, E. J. Chem. Soc., Perkin Trans. 1, 1979, 138-141; Ducrocq, C.; Bisagni, E.; Rivalle, C.; Lhoste, J-M. ibid., 1979, 142-145; Moustacchi, E.; Favaudon, V.; Bisagni, E. Cancer Res., 1983, 43, 3700-3706; Fontaine-Aupart, M.P.; Laguitton-Pasquier, H.; Pansu, R.; Brian, L.; Renault, E.; Marden, M.C.; Rivalle, C.; Bisagni, E. J. Chem.Soc., Perkin Trans. 2, 1996, 1767-1774.
34. see, for example, Rivalle, C.; Ducrocq, C.; Bisagni, E. J. Chem. Soc., Perkin Trans. 1, 1979, 138-141; Ducrocq, C.; Bisagni, E.; Rivalle, C.; Lhoste, J-M. ibid., 1979, 142-145; Moustacchi, E.; Favaudon, V.; Bisagni, E. Cancer Res., 1983, 43, 3700-3706; Fontaine-Aupart, M.P.; Laguitton-Pasquier, H.; Pansu, R.; Brian, L.; Renault, E.; Marden, M.C.; Rivalle, C.; Bisagni, E. J. Chem.Soc., Perkin Trans. 2, 1996, 1767-1774.
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36. Measured by titration of 2 (0.054 g) in ethanol (5 ml) against 0.1019 M HCl using a Crison digilab 517 pH meter following standard procedures (Albert, A.A.; Sarjeant, E.P. The Determination of Ionisation Constants, Chapman and Hall, London, 1971)
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