Advertisement

Chemotherapy pp 167-181 | Cite as

Analogues and Metabolites of Cyclophosphamide

  • K. Norpoth

Abstract

In 1969 I proposed a mechanism of biological Cyclophosphamide (CYM) activation ( 18) which is shown by figure 1. This pathway was concluded from circumstantial evidence that 4-carboxy-CYM is the main CYM metabolite and the C-4 atom of the molecule ring is the preferential site of biological oxidation. I assumed that one of the metabolites should account for the tumour specific activity of the drug. This we could rule out concerning 4-carboxyCYM although this compound has been identified as the main metabolite by Struck and co-workers in addition to 4-keto-CYM, a non toxic minor metabolite (27).

Keywords

Urine Metabolite Anthranilic Acid Chloroacetic Acid Test Tumour Phosphoramide Mustard 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Alarcon, R.A. and Meienhofer, J. (1971). Nature, New Biology, 233, 250–252.Google Scholar
  2. 2.
    Alarcon, R.A., Meienhofer, J. and Atherton, E. (1972). Cancer Research, 32, 2519–2523.PubMedGoogle Scholar
  3. 3.
    Alarcon, R.A. Symposium on Metabolism and Mechanism of Action of Cyclophosphamide, London July 10th-12th, 1975. (In press)Google Scholar
  4. 4.
    Ardenne, M. von, Reitnauer, P.G. and Rohde, K. (1971). Arch. Geschwulstforsch, 38, 15–26.Google Scholar
  5. 5.
    Bakke, J.E., Feil, V. J., Fjeilstul, C.E. and Thacker, E.J. (1972). J.Agr.Food Chem., 20, 384.CrossRefGoogle Scholar
  6. 6.
    Benckhuysen, C., Van Der Steen, J. and Spanjersberg, E.J. Symposium on Metabolism and Mechanism of Action of Cyclophosphamide, London, July 10th-12th 1975 (In press).Google Scholar
  7. 7.
    Brock, N. Symposium on Metabolism and Mechanism of Action of Cyclophosphamide, London, July 10th-12th 1975 (In press)Google Scholar
  8. 8.
    Brock, N. (1972). Czechoslowak Medical Press, Vol. II, Avicenum, Prague, p. 749–756.Google Scholar
  9. 9.
    Connors, T.A., Cox, P.J., Farmer, P.B., Foster, A.B., Jarman, M. and Macleod, J.K. ( 1974). Biomedical Mass Spectrometry, 1, 130–136.PubMedCrossRefGoogle Scholar
  10. 10.
    Connors, T.A., Farmer, P.B., Foster, A.B. and Jarman, M. (1974). Biochem. Pharmacol., 23, 115–129.PubMedCrossRefGoogle Scholar
  11. 11.
    Cox, P.J., Farmer, P.B., Foster, A.B., Gilby, E.D. and Jarman, M. Symposium on Metabolism and Mechanism of Action of Cyclophosphamide. London, July 10th-12th, 1975 (In press).Google Scholar
  12. 12.
    Druckrey, H. (1970). J. Kanser (Ankara), 1, 131–149.Google Scholar
  13. 13.
    Hill, D.L., Laster, W.R., Jr. and Struck, R.F. (1972). Cancer Research, 32, 658–665.PubMedGoogle Scholar
  14. 14.
    Hill, D.L., Laster, W.R., Jr., Kirk, M.C., El Dreer, S. and Struck, R.F. (1973). Cancer Research, 33, 1016–1022.PubMedGoogle Scholar
  15. 15.
    Hohorst, H.J. ( 1973). Paper held at the second meeting of the European Association for Cancer Research, Heidleberg, October 2–5th.Google Scholar
  16. 16.
    Kaye, C.M. (1973). Biochem. J., 134, 1093–1101.PubMedGoogle Scholar
  17. 17.
    Kaye, C.M. and Joung, (1974). Biochem. Soc. Trans. 2, 308.Google Scholar
  18. 18.
    Norpoth, K. (1969). Habilitationsschrift, Munster.Google Scholar
  19. 19.
    Norpoth, K., Addicks, H.W. and Witting, U. (1973). Arzneim. Forsch. (Drug Res.), 23, 1529–1535.Google Scholar
  20. 20.
    Norpoth, K., Wust, G. and Witting, U. (1972). Verhandlungen der Deutschen Gesellschaft fur Innere Medizin, 78, 1561–1564.PubMedGoogle Scholar
  21. 21.
    Norpoth, K. Symposium on Metabolism and Mechanism of Action of Cyclophosphamide, London, July 10–12th, 1975.Google Scholar
  22. 22.
    Norpoth, K., Witting, U. and Rauen, H.M. (1974). Arzneim. Forsch. (Drug Res.), 24, 86–89.Google Scholar
  23. 23.
    Norpoth, K. and Witting, U. Unpublished results.Google Scholar
  24. 24.
    Peter, G. and Hohorst, H.J. Symposium on Metabolism and Mechanism of Action of Cyclophosphamide. London, July 10–12th, 1975. ( In press).Google Scholar
  25. 25.
    Sawicki, E., Bender, D.F., Hanser, T.R., Wilson, R.M. and Meeker, J.E. (1963). Anal. Chem., 35, 1479–1486.CrossRefGoogle Scholar
  26. 26.
    Sawicki, E. and Sawicki, C.R. (1969). Ann. N.Y. Acad. Sci., 163, 895–920.CrossRefGoogle Scholar
  27. 27.
    Struck, R.F., Kirk, M.C, Mellet, L.B., El Dareer, S. and Hill, D.L. (1971). Molecular Pharmacology, 7, 519–529.PubMedGoogle Scholar
  28. 28.
    Struck, R.F. (1974). Cancer Research, 34, 2933–2935.PubMedGoogle Scholar
  29. 29.
    Takamizawa, A., Matsumoto, S., Iwata, T., Katagiri, K., Tochino, Y. and Yamaguchi, K. (1973). J. Am. Chem. Soc, 95, 985–986.CrossRefGoogle Scholar
  30. 30.
    Takamizawa, A., Matsumoto, S. and Iwata, T. (1974). Tetrahedron Letters, 6, 517–520.CrossRefGoogle Scholar
  31. 31.
    Takamizawa, A., Iwata, T., Matsumoto, S., Yamagucki, K., Shiratory, O., Harada, M. and Tochino, Y. Symposium on Metabolism and Mechanism of Action of Cyclophosphamide. London, July 10–12th, 1975. (In press).Google Scholar
  32. 32.
    Whitehouse, M.W., Beck, F.J. and Kacena, A. (1974). Agents and Action, 4, 1.CrossRefGoogle Scholar
  33. 33.
    Yllner, S. (1971). Acta pharmacol. et toxicol., 30, 69–80.CrossRefGoogle Scholar
  34. 34.
    Yllner, S. (1971). Acta pharmacol. et toxicol., 30, 257–265.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • K. Norpoth
    • 1
  1. 1.Institute for Pneumoconiosis Research and Occupational MedicineUniversity of MuensterGerman Federal Republic

Personalised recommendations