Skip to main content
SpringerLink
Log in

Solvent Effects on the Structure-Activity Relationship of Pharmacological Active 3-Substituted-5,5-Diphenylhydantoins

  • Original Paper
  • Published:
Journal of Solution Chemistry Aims and scope Submit manuscript

Abstract

Absorption spectra of eight 3-substituted-5,5-diphenylhydantoins have been recorded in fourteen solvents in the range 200–400 nm. The effect of solvent dipolarity/polarizability and solvent/solute hydrogen bonding interactions are analyzed by means of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The lipophilic activity of the investigated hydantoins was estimated by the calculation of log 10 P values with the Advanced Chemistry Development Software. The calculated values of log 10 P were correlated with the ratio of the contributions of specific solvent interactions, and, by employing the linear dependence thus obtained, the pharmacological activity of the studied hydantoin derivatives is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lopez, A.C., Trigo, C.G.: In: Katrizky, A.R. (ed.) The Chemistry of Hydantoins. Advances in Heterocyclic Chemistry. Academic Press, New York (1985)

    Google Scholar 

  2. Scholl, S., Koch, A., Henning, D., Kempter, G., Kleinpeter, E.: The influence of structure and lipophilicity of hydantoin derivatives on anticonvulsant activity. Struct. Chem. 10, 355–366 (1999)

    Article  CAS  Google Scholar 

  3. Knabe, J., Baldauf, J., Ahlhem, A.: Racemates and enantiomers of basic substituted 5-phenylhydantoins. Syntheses and antiarrhythmic activity. Pharmazie 52, 912–919 (1997)

    CAS  Google Scholar 

  4. Anger, T., Madge, D.J., Mulla, M., Riddall, D.: Medicinal chemistry of neuronal voltage-gated sodium channel blockers. J. Med. Chem. 44, 115–137 (2001)

    Article  PubMed  CAS  Google Scholar 

  5. Kleinpeter, E.: The structure of hydantoins in solution and in the solid state. Struct. Chem. 8, 161–173 (1997)

    Article  CAS  Google Scholar 

  6. Rodgers, T.R., LaMontagne, M.P., Markovac, A., Ach, A.B.: Hydantoins as antitumor agents. J. Med. Chem. 20, 591–594 (1977)

    Article  PubMed  CAS  Google Scholar 

  7. Meldrum, B.S.: Identification and preclinical testing of novel antiepileptic compounds. Epilepsia 38, S7–S15 (1997)

    PubMed  CAS  Google Scholar 

  8. Seydel, J.K., Schaper, K.J.: In: Schemische Struktur und Biologische Wirkung von Wirkstoffen, Metoden der Quantitativen Structur–Wirkungsanalyse. Verlag Chemie, Weinheim (1979)

    Google Scholar 

  9. Hacksell, U.: In: Krogsgaard-Larsen, P., Madsen, U. (eds.) A Textbook of Drug Design and Development. Harwood Academic Publishers, Amsterdam (1996)

    Google Scholar 

  10. Brouillette, W.J., Brown, G.B., DeLorey, T.M., Liang, G.: Sodium channel binding and anticonvulsant activities of hydantoin containing conformationally constrained 5-phenyl substituents. J. Pharm. Sci. 79, 871–874 (1990)

    Article  PubMed  CAS  Google Scholar 

  11. Brouillette, W.J., Jestkov, V.P., Brown, M.L., Akhtar, M.S., DeLorey, T.M., Brown, G.B.: Bicyclic hydantoins with a bridgehead nitrogen. Comparison of anticonvulsant activities with binding to the neuronal voltage-dependent sodium channel. J. Med. Chem. 37, 3289–3293 (1994)

    CAS  Google Scholar 

  12. Unverferth, K., Engel, J., Höfgen, N., Rostock, A., Günther, R., Lankau, H.J., Menzer, M., Rolfs, A., Liebscher, J., Müller, B., Hofmann, H.J.: Synthesis. anticonvulsant activity, and structure-activity relationships of sodium channel blocking 3-aminopyrroles. J. Med. Chem. 41, 63–73 (1998)

    CAS  Google Scholar 

  13. Poupaert, J.H., Vandervarst, D., Guiot, P., Moustafa, M.M.M., Dumont, P.: Structure–activity relationship of phenytoin-like anticonvulsant drugs. J. Med. Chem. 27, 76–78 (1984)

    Article  PubMed  CAS  Google Scholar 

  14. Jones, G.L., Woodbury, D.M.: Anticonvulsant structure–activity relationships: historical development and probable causes of failure. Drug Dev. Res. 2, 333–355 (1982)

    Article  CAS  Google Scholar 

  15. Kamlet, M.J., Abboud, J.L.M., Taft, R.W.: An examination of linear solvation energy relationships. Prog. Phys. Org. Chem. 13, 485–630 (1981)

    Article  CAS  Google Scholar 

  16. Abboud, J.L.M., Kamlet, M.J., Taft, R.W.: Regarding a generalized scale of solvent polarities. J. Am. Chem. Soc. 99, 8325–8327 (1977)

    Article  CAS  Google Scholar 

  17. Kamlet, M.J., Taft, R.W.: The solvatochromic comparison method. I. The β-scale of solvent hydrogen-bond acceptor (HBA) basicities. J. Am. Chem. Soc. 98, 377–383 (1976)

    Article  CAS  Google Scholar 

  18. Kamlet, M.J., Taft, R.W.: Linear solvation energy relationships. Part 3. Some reinterpretations of solvent effects based on correlations with solvent π * and α values. J. Chem. Soc. Perkin Trans. 2, 349–356 (1979)

    Google Scholar 

  19. Kamlet, M.J., Doherty, R.M., Abboud, J.L.M., Abraham, M.H., Taft, R.W.: Solubility: a new look. Chemtech 16, 566–576 (1986)

    CAS  Google Scholar 

  20. Carr, P.W., Doherty, R.M., Kamlet, M.J., Taft, R.W., Melander, W., Horvath, C.: Study of temperature and mobile-phase effects in reversed-phase high–performance liquid chromatography by the use of the solvatochromic comparison method. Anal. Chem. 58, 2674–2680 (1986)

    Article  PubMed  CAS  Google Scholar 

  21. Ušćumlić, G.S., Mijin, D.Ž., Valentić, N.V., Vajs, V., Sušić, B.: Substituent and solvent effects on the UV/Vis absorption spectra of 5-(4-substituted arylazo)-6-hydroxy-4-methyl-3-cyano-2-pyridones. Chem. Phys. Lett. 397, 148–153 (2004)

    Article  Google Scholar 

  22. Mijin, D.Ž., Ušćumlić, G.S., Perišić-Janjić, N.U., Valentić, N.V.: Substituent and solvent effects on the UV/vis absorption spectra of 5-(3- and 4-substituted arylazo)-4,6-dimethyl-3-cyano-2-pyridones. Chem. Phys. Lett. 418, 223–229 (2006)

    Article  CAS  Google Scholar 

  23. Magnes, B.Z., Pines, D., Strashnikova, N., Pines, E.: Hydrogen-bonding interactions of photoacids: Correlation of optical solvatochromism with IR absorption spectra. Solid State Ionics 168, 225–233 (2004)

    Article  CAS  Google Scholar 

  24. Spange, S., Kunzmann, D., Sens, R., Roth, I., Seitfert, A., Thiel, W.R.: Solvatochromic azamethine dyes for probing the polarity of gold-cluster-functionalized silica particles. Chem. Eur. J. 9, 4161–4167 (2003)

    Article  CAS  Google Scholar 

  25. Vida, J.A., Samour, C.M., Reinhard, J.F.: Anticonvulsants. 1. Alkoxymethyl derivatives of barbiturates and diphenylhydantoin. J. Med. Chem. 14, 187–189 (1971)

    Article  PubMed  CAS  Google Scholar 

  26. Mai, K.H.X., Patil, G.: Preparation of 2-(1-hydroxyalkyl)-5,5-diphenylhydantoins as drug intermediates. U.S. Patent 4,709,042 (1987); Chem. Abstr. 108, 94560 (1987)

  27. Vida, J.A., Wilber, W.R., Reinhard, J.F.: Anticonvulsants. 2. Acyloxymethyl and halomethyl derivatives of barbituric acid and diphenylhydantoin. J. Med. Chem. 14, 190–193 (1971)

    Article  CAS  Google Scholar 

  28. Hoffmann, C.: Synthesis of some 3-substituted 5,5-diphenylhydantoins. Bull. Soc. Chim. Fr., 45–47 (1950)

  29. Muccioli, G.G., Wouters, J., Poupaert, J.H., Norberg, B., Poppitz, W., Scriba, E.K.G., Lambert, D.M.: Versatile access to benzhydryl-phenylureas through an unexpected rearrangement during microwave-enhanced synthesis of hydantoins. Org. Lett. 5, 3599–3602 (2003)

    Article  PubMed  CAS  Google Scholar 

  30. Kamlet, M.J., Abboud, J.L.M., Abraham, M.H., Taft, R.W.: Linear solvation energy relationships. 23. A comprehensive collection of the solvatochromic parameters, π *, α, and β, and some methods for simplifying the generalized solvatochromic equation. J. Org. Chem. 48, 2877–2887 (1983)

    Article  CAS  Google Scholar 

  31. Taft, R.W., Abboud, J.-L.M., Kamlet, M.J.: Solvatochromic comparison method. 20. Linear solvation energy relationships. 12. The dδ term in the solvatochromic equations. J. Am. Chem. Soc. 103, 1080–1086 (1981)

    Article  CAS  Google Scholar 

  32. Ušćumlić, G.S., Kshad, A.A., Mijin, D.Ž.: Synthesis and investigation of solvent effects on the ultraviolet absorption spectra of 1,3-bis-substituted-5,5-dimethylhydantoins. J. Serb. Chem. Soc. 68, 699–706 (2003)

    Article  Google Scholar 

  33. Ware, E.: The chemistry of the hydantoins. Chem. Rev. 46, 403–70 (1950)

    Article  CAS  Google Scholar 

  34. Vida, J.A., O’Dea, M.H., Samour, C.M., Reinhard, J.F.: Anticonvulsants. 5. Derivatives of 5-ethyl-5-phenylhydantoin and 5,5-diphenylhydantoin. J. Med. Chem. 18, 383–385 (1975)

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Organic Chemistry, Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, PO Box 3503, 11120, Belgrade, Serbia

    Nebojša Banjac, Gordana Ušćumlić, Nataša Valentić & Dušan Mijin

Authors
  1. Nebojša Banjac
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gordana Ušćumlić
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nataša Valentić
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dušan Mijin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nataša Valentić.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Banjac, N., Ušćumlić, G., Valentić, N. et al. Solvent Effects on the Structure-Activity Relationship of Pharmacological Active 3-Substituted-5,5-Diphenylhydantoins. J Solution Chem 36, 869–878 (2007). https://doi.org/10.1007/s10953-007-9153-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10953-007-9153-2

Keywords

Search

Navigation