Abstract
Solubilities of tricyclic analogs of acyclovir have been determined in water at 25, 35, and 45°C and in octanol, water-saturated octanol, and octanol-saturated water at 25°C. Octanol-water partition coefficients were determined at 25°C. Melting temperatures and molar enthalpies of fusion were measured. Activity coefficients in water, octanol, and in aqueous octanol solutions were determined and are discussed. The effect of hydrophilic and hydrophobic substituents in the tricyclic analogs on their thermodynamic properties are discussed. The standard Gibbs energy of transfer between the saturated phases were found to correlate with known values of the melting point of the solvents and the solubilities of the solute. For a number of the compounds examined, correlations between the minimum inhibitory concentration against the herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), thymidine kinase-deficient (TK−) strains of VZV and \(\Delta G_{{\text{W}} \to {\text{0}}}^0 ;\Delta G_{{\text{tr}}}^0\) were established. Detailed conclusions have been derived concerning the relationships between the structure and the thermodynamic parameters of the compounds examined.
Similar content being viewed by others
REFERENCES
C. Hansch and A. Leo, Substituent Constants for Correlation Analysis in Chemistry and Biology (Wiley, New York, 1979).
F. G. Topliss, Quantitative Structure Activity Relationships of Drugs (Academic Press, New York, 1983).
A. Leo, C. Hansch, and D. Elkins, Chem. Rev. 71, 525 1971.
H. Fujiwara, Yong-Zhong Da, K. Ito, T. Takagi, and Y. Nishioka, Bull. Chem. Soc. Jpn. 64, 3770 (1991).
C. Yamagami, K. Iwasaki, and A. Ishikawa, Chem. Pharm. Bull. 45, 1653 (1997).
Yong-Zhong Da, K. Ito, and H. Fujiwara, J. Med. Chem. 35, 3382 (1992).
B. Golankiewicz, T. Ostrowski, G. Andrei, R. Snoeck, and E. De Clercq, J. Med. Chem. 37, 3187 (1994).
J. Czaplicki, T. Bohner, A.-K. Habermann, G. Folkers, and A. Milon, J. Biomol. NMR 8, 261 (1996).
J. Boryski and B. Golankiewicz, Nucleosides, Nucleotides 8, 529 (1989).
J. Boryski, B. Golankiewicz, and E. De Clercq, J. Med. Chem. 31, 1351 (1988).
J. Boryski, B. Golankiewicz, and E. De Clercq, J. Med. Chem. 34, 2380 (1991).
S. I. Sandler, Chemical and Engineering Thermodynamics, 2nd ed. (Wiley New York, 1989), p. 408.
J. M. Prausnitz, R. N. Lichenthaler, and E. G. de Azevedo, Molecular Thermodynamics of Fluid-Phase Equilibria (Prentice-Hall, Englewood Cliffs, New Jersey 1986).
A. Kristl and G. Vesnaver, J. Chem. Soc. Faraday Trans. 91, 995 (1995).
J. H. Hildebrand and R. L. Scott, Regular Solutions, (Prentice-Hall, Englewood Cliffs, New Jersey, 1962).
N. R. Draper, H. Smith, Applied Regression Analysis (Wiley, New York, 1973), p. 459.
J. H. Smith, C. Hansch, and M. M. Ames, J. Pharm. Sci. 64, 599 (1975).
N. P. Franks, M. N. Abraham, and W. R. Lieb, J. Pharm. Sci. 82, 466 (1993).
M. Iwahashi, Y. Hayashi, N. Hachiya, H. Matsuzawa, and H. Kobayashi, J. Chem. Soc. Faraday Trans. 89, 707 (1993).
B. C. Lippold and M. S. Adel, Arch. Pharm. 305, 417 (1972).
A. J. Dallas and P. W. Carr, J. Chem. Soc. Perkin Trans. 2, 2155 (1992).
S. H. Yalkowsky and S. Banerjee, Aqueous Solubility (Marcel Dekker, New York, 1992).
A. Kristl, J. Chem. Soc. Faraday Trans. 92, 1721 (1996).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zielenkiewicz, W., Golankiewicz, B., Perlovich, G.L. et al. Aqueous Solubilities, Infinite Dilution Activity Coefficients and Octanol–Water Partition Coefficients of Tricyclic Analogs of Acyclovir. Journal of Solution Chemistry 28, 731–745 (1999). https://doi.org/10.1023/A:1021720128725
Issue Date:
DOI: https://doi.org/10.1023/A:1021720128725