Abstract
Using the PCILO method and the supermolecule approach, the hydration of the acid and base forms of the closely related pairs of compounds, oxymorphone and hydromorphone, and oxycodone and hydrocodone, have been studied. The presence of the axial C14—OH group in the oxy compounds causes a substantial increase in total hydration energy and an increase in proton affinity. These two effects should combine to cause a lowering of both apparent and intrinsic partition coefficients as well as provide an explanation of the observed increase in pK a of the oxy compounds.
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References
Mellett, L. B. and Woods, L. A.: Prog. Drug Res. 5, 156 (1963).
Kutter, E., Herz, A., Teschemacher, H.-J., and Hess, R.: J. Med. Chem. 13, 801 (1970).
Leo, A., Hansch, C., and Elkins, D.: Chem. Rev. 71, 525 (1971).
Hansch, C.: in C. J. Cavallito (ed.), Structure Activity Relationships, Section 5, Vol. 1, Pergamon Press, 1973, p. 75.
Meyerhoffer, A.: F.O.A. Reports (Research Inst. Nat. Defense - Sweden) Vol. 3, No. 13 (1973).
Pullman, A. and Pullman, B.: Quart. Rev. Biophys. 7, 505 (1975) and references therein.
Weinstein, H., Srebrenik, S., Mayani, S., and Sokolovsky, M.: Mol. Pharmacol. (1975).
Karle, I. L.: Acta Cryst. B30, 1682 (1974).
Diner, S., Malrieu, J. P., Jordan, F., and Gilliert, M.: Theoret. Chim. Acta 15, 100 (1969) and references therein.
Srebrenik, S., Weinstein, H., and Pauncz, R.: Chem. Phys. Letters 20, 419 (1973).
Alagona, A., Cimiraglia, R., Scrocco, E., and Tomasi, J.: Theoret. Chim. Acta 25, 103 (1972).
Kollman, P. and Allen, L. C.: J. Am. Chem. Soc. 93, 4991 (1971).
Bernath, G. and Koczka, K.: Chem. and Ind. (London), 1479 (1960).
Rappoport, H.: J. Am. Chem. Soc. 77, 4330 (1955).
Jolliffe, G. O. and Ahmad, M. M.: Bull. on Narcotics XXIII, 37 (1971).
Kaufman, J. J., Koski, W. S., and Semo, N.: J. Med. Chem. in press; personal communication, May, 1975.
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© 1976 D. Reidel Publishing Company, Dordrecht-Holland
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Loew, G., Weinstein, H., Berkowitz, D. (1976). Theoretical Study of the Solvent Effect on Ionization and Partition Behavior in Related Opiate Narcotics: Hydromorphone and Oxymorphone. In: Pullman, B. (eds) Environmental Effects on Molecular Structure and Properties. The Jerusalem Symposia on Quantum Chemistry and Biochemistry, vol 8. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-1837-1_15
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DOI: https://doi.org/10.1007/978-94-010-1837-1_15
Publisher Name: Springer, Dordrecht
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