Skip to main content
SpringerLink
Log in

Partitioning of Free Energies of Solvation into Fragment Contributions: Applications in Drug Design

  • Chapter
Fundamentals of Molecular Similarity

Part of the book series: Mathematical and Computational Chemistry ((MACC))

Abstract

It is recognised that solvation influences the activity of therapeutic agents at two different levels [1–6]: i) the binding with the receptor, and ii) the bioavailability of the drug in the organism. These aspects are complementary in drug discovery in the sense that lead optimisation should ideally concentrate on compounds having tight binding affinity and favorable ADME (absorption, distribution, metabolism, excretion) properties.

Send correspondence to F. J. Luque or M. Orozco

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Hansch, P. P. Maloney, T. Fujita and R. Mui, Nature 194, 178 (1963).

    Article  Google Scholar 

  2. Hansch , Acc. Chem. Res. 2, 232 (1969).

    Article  CAS  Google Scholar 

  3. Leo, C. Hansch and D. Elkins, Chem Rev. 71, 525 (1971).

    Article  CAS  Google Scholar 

  4. Y. C. Martin, Quantitative Drug Design: A Critical Introduction, Marcel Decker, NY (1978).

    Google Scholar 

  5. L. Horvath, Molecular Desing. Elsevier, Amsterdam (1992).

    Google Scholar 

  6. Hansch and A. Leo, Exploring QSAR: Fundaments and Applications in Chemistry and Biology, ACS, Washington DC (1995).

    Google Scholar 

  7. Hansch and A. Leo, Substituent Constants for Correlation Analysis in Chemistry and Biology, John Wiley, New York (1979).

    Google Scholar 

  8. G. Nys and R. F. Rekker, Chim. Therap. 8, 521 (1973).

    CAS  Google Scholar 

  9. Hopfinger and R. D. Battershell, J. Med. Chem. 19, 569 (1976).

    Article  CAS  Google Scholar 

  10. R. F. Rekker, The Hydrophobic Fragmental Constant, Elsevier, Amsterdam (1977).

    Google Scholar 

  11. Klopman and L. Iroff, J. Comp. Chem. 2, 157 (1981).

    Article  CAS  Google Scholar 

  12. K. Iwase, K. Komatsu, S. Hirono, S. Nakagawa and I. Moriguchi, Chem. Pharm. Bull. 33, 2114 (1985).

    Article  CAS  Google Scholar 

  13. Y. Suzuki and Y. Kudo, J. Comput-Aided Mol. Des. 4, 155 (1990).

    Article  CAS  Google Scholar 

  14. N. Bodor, Z. Gabany and C. K. Wong, J. Am. Chem. Soc. 111, 3783 (1989).

    Article  CAS  Google Scholar 

  15. K. Ghose and G. M. Crippen, J. Comput. Chem. 7, 565 (1986).

    Article  CAS  Google Scholar 

  16. V. N. Viswanadhan, A.K. Ghose, G. R. Revenkar and R. Robins, J. Chem. Inf. Comput. Sci. 29, 163 (1989).

    Article  CAS  Google Scholar 

  17. G. Klopman and S. Wang, J. Comput. Chem. 12, 1025 (1991).

    Article  CAS  Google Scholar 

  18. W. M. Meylan and P. H. Howard, J. Pharm. Sci. 84, 83 (1995).

    Article  CAS  Google Scholar 

  19. R. Mannhold and K. Dross, Quant. Struct.-Act Relat. 15, 403 (1996).

    Article  CAS  Google Scholar 

  20. R. Wang, Y. Fu and L. Lai, J. Chem. Inf. Comput. Sci. 37, 615 (1997).

    Article  CAS  Google Scholar 

  21. V. Gombar and K. Enslein, J. Chem. Inf. Comput. Sci. 36, 1127 (1996).

    Article  CAS  Google Scholar 

  22. S. C. Basak, B. D. Gute and G. D. Grunwald, J. Chem. Inf. Comput. Sci. 36, 1054 (1996).

    Article  CAS  Google Scholar 

  23. van de Waterbeemd and R. Mannhold, Quant. Struct.-Act. Relat. 15, 410 (1996).

    Article  Google Scholar 

  24. T. Convard, J. P. Dubost, H. Le Solleu and E. Kummer, Quant. Struct.-Act. Relat. 13, 34 (1994).

    CAS  Google Scholar 

  25. M. A. Gallop, et al., J. Med. Chem. 37, 1233 (1994).

    Article  CAS  Google Scholar 

  26. M. Gordon, et al., J. Med. Chem. 37, 1385 (1994).

    Article  CAS  Google Scholar 

  27. J. Martin, J. M. Blaney, M. A. Siani, D. C. Spellmeyer, A. K. Wong and W. H. Moos, J. Med. Chem. 38, 1431 (1995).

    Article  CAS  Google Scholar 

  28. W. P. W. Ajay and M. A. Murcko, J. Med. Chem. 41, 3314 (1998).

    Article  CAS  Google Scholar 

  29. Sadowski and H. Kubinyi, J. Med. Chem. 41, 3325 (1998).

    Article  CAS  Google Scholar 

  30. P. W. Finn, Drug. Disc. Today 1, 363 (1996).

    Article  CAS  Google Scholar 

  31. R. Carbó, L. Leyda and M. Arnau, Int. J. Quantum Chem. 17, 1185 (1980).

    Article  Google Scholar 

  32. R. Carbó (ed.), Molecular Similarity and Reactivity: From Quantum Chemical to Phenomenological Approaches, Kluwer, Amsterdam (1995).

    Google Scholar 

  33. R. Carbó-Dorca and P. G. Mezey (eds.), Advances in Molecular Similarity, Vol. 1, JAI Press, Greenwich, CT (1996).

    Google Scholar 

  34. Gorse, A. Rees, M. Kaczorek and R. Lahana, Drug Disc. Today 4, 257 (1999).

    Article  CAS  Google Scholar 

  35. M. Ter Laak, R. S. Tsai, G. M. Donné-Op den Kelder, P. A. Carrupt, B. Testa and H. Timmerman, Eur. J. Pharm. Sci. 2, 373 (1994).

    Article  Google Scholar 

  36. R. Mannhold, K. P. Dross and R. F. Rekker, Quant. Struct.-Act. Relat. 9, 21 (1990).

    Article  CAS  Google Scholar 

  37. P. Artursson and J. Karlsson, Biochem. Biophys. Res. Commun. 175, 880 (1991).

    Article  CAS  Google Scholar 

  38. M. Orozco, C. Alhambra, X. Barril, J. M. López, M. A. Busquets and F. J. Luque, J. Mol. Model. 2, 1 (1996).

    Article  Google Scholar 

  39. W. L. Jorgensen, in Computer Simulation of Biomolecular Systems: Theoretical and Experimental Applications, W.F van Gunsteren and P.K. Weiner (eds.), ESCOM, Leiden (1989), p. 60.

    Google Scholar 

  40. L. Rivail and D. Rinaldi, in Computational Chemistry, Review of Current Trends, J. Leszcynski (ed.), Word Scientific Publishing, Singapore (1996), p. 139.

    Chapter  Google Scholar 

  41. J. Tomasi and M. Persico, Chem. Rev. 94, 2027 (1994).

    Article  CAS  Google Scholar 

  42. J. Cramer and D. G. Truhlar, in Solvent Effects and Chemical Reactivity, O. Tapia and J. Bertrán (eds.), Kluwer Academic Publishers, Dordrecht (1996), p. 1.

    Google Scholar 

  43. J. Cramer and D. G. Truhlar, Chem. Rev. 99, 2161 (1999).

    Article  CAS  Google Scholar 

  44. J. Luque, X. Barril and M. Orozco, J. Comput.Aided Mol. Design 13, 139 (1999).

    Article  CAS  Google Scholar 

  45. J. Giesen, C. C. Chambers, C. J. Cramer and D. G. Truhlar, J. Phys. Chem. B 101, 5084 (1997).

    Article  CAS  Google Scholar 

  46. D. Hawkins, C. J. Cramer and D. G. Truhlar, J. Phys. Chem. B 102, 3257 (1998).

    Article  CAS  Google Scholar 

  47. S. Miertus, E. Scrocco and J. Tomasi, Chem.Phys. 55, 117 (1981).

    Article  CAS  Google Scholar 

  48. S. Miertus and J. Tomasi, Chem.Phys. 65, 239 (1982).

    Article  CAS  Google Scholar 

  49. J. S. Dewar and W. Thiel, J. Am Chem. Soc. 99, 4899 (1977).

    Article  CAS  Google Scholar 

  50. J. S. Dewar, E. G. Zoebisch, E. F. Horsley and J. J. P. Stewart, J. Am. Chem. Soc. 107, 3902 (1985).

    Article  CAS  Google Scholar 

  51. J. J. P. Stewart, J. Comput. Chem. 10, 209 (1989).

    Article  CAS  Google Scholar 

  52. P. C. Hariharan and J. A. Pople, Theor. Chim. Acta 28, 213 (1973).

    Article  CAS  Google Scholar 

  53. J. Luque, M. J. Negre and M. Orozco, J.. Phys. Chem. 97, 4386 (1993).

    Article  CAS  Google Scholar 

  54. Orozco and F. J. Luque, Chem. Phys. 182, 237 (1994).

    Article  CAS  Google Scholar 

  55. M. Bachs, F. J. Luque and M. Orozco, J. Comput. Chem. 15, 446 (1994).

    Article  CAS  Google Scholar 

  56. J. Luque, M. Bachs and M. Orozco, J. Comput. Chem. 15, 847 (1994).

    Article  CAS  Google Scholar 

  57. M. Orozco, M. Bachs and F. J. Luque, J. Comput. Chem. 16, 563 (1995).

    Article  CAS  Google Scholar 

  58. J. Luque, M. Bachs, C. Alemán and M. Orozco, J. Comput. Chem. 17, 806 (1996).

    Article  CAS  Google Scholar 

  59. J. Luque, Y. Zhang, C. Alemán, M. Bachs, J. Gao and M. Orozco, J. Phys. Chem. 100, 4269 (1996).

    Article  CAS  Google Scholar 

  60. L. Coitiño, J. Tomasi and R. Cammi, J. Comput. Chem. 16, 20 (1995).

    Article  Google Scholar 

  61. R. Cammi and J. Tomasi, J. Comput. Chem. 16, 1449 (1995).

    Article  CAS  Google Scholar 

  62. R. A. Pierotti, Chem. Rev. 76, 717 (1976).

    Article  CAS  Google Scholar 

  63. Claverie, in Intermolecular Interactions: From Diatomics to Biomolecules, B. Pullman (ed.), Wiley, Chichester (1978).

    Google Scholar 

  64. J. Luque, J. M. Bofill and M. Orozco, J. Chem. Phys. 103, 10183 (1995).

    Article  CAS  Google Scholar 

  65. J. G. Ángydn, J. Chem. Phys. 107, 1291 (1997).

    Article  Google Scholar 

  66. F. J. Luque, J. M. Bofill and M. Orozco, J. Chem. Phys. 107, 1293 (1997).

    Article  CAS  Google Scholar 

  67. F. J. Luque and M. Orozco, J. Phys. Chem. 101, 5573 (1997).

    CAS  Google Scholar 

  68. M. Orozco, R. Roca, C. Alemán, M. A. Busquets, J. M. López and F. J. Luque, J. Mol. Struct. (THEOCHEM) 371, 269 (1996).

    Article  CAS  Google Scholar 

  69. L. H. Krarup, I. T. Christensen, L. Hovgaard and S. Frokjaer, Pharm. Res. 15, 972 (1998).

    Article  CAS  Google Scholar 

  70. K. Palm, K. Luthman, A.-L. Ungell, G. Strandlund and P. Artursson, J. Pharn Sci. 85, 32 (1996).

    Article  CAS  Google Scholar 

  71. K. Palm, K. Luthman, A.-L. Ungell, G. Strandlund, F. Beigi, P. Lundahl and P. Artursson, J. Med. Chem. 41, 5382 (1998).

    Article  CAS  Google Scholar 

  72. D. E. Clark, J. Pharm. Sci. 88, 815 (1999).

    Article  CAS  Google Scholar 

  73. S. C. Basak, B. D. Gute and L. R. Drewes, Pharm. Res. 13, 775 (1996).

    Article  CAS  Google Scholar 

  74. M. H. Abraham, K. Takacs-Novak and R. C. Mitchell, J. Pharm. Sci. 86, 310 (1997).

    Article  CAS  Google Scholar 

  75. Artursson and J. Karisson, Biochem. Biophys. Res. Commun. 175, 880 (1991).

    Article  CAS  Google Scholar 

  76. L. Amidon, P. J. Sinko and D. Fleisher, D., Pharm. Res.5, 651 (1988).

    Article  CAS  Google Scholar 

  77. J. P. Stewart, MOPAC-93 Rev. 2. Fujitsu Limited, 1993. Modified by F. J. Luque and M. Orozco, University of Barcelona, Barcelona (1997).

    Google Scholar 

  78. F. J. Luque, J. M. López-Bes, J. Cemeli, M. Aroztegui and M. Orozco, Theor. Chem. Acc. 96, 105 (1997).

    Article  CAS  Google Scholar 

  79. D. R. Lide (ed.), Handbook of Organic Solvents, CRC Press, Boca Raton, FL (1995).

    Google Scholar 

  80. V. Segarra, M. Lopez, H. Ryder and J. M. Palacios, Quant. Struct. Act. Relat. 18, 474 (1999).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departament de Fisicoquímica, Facultat de Farmàcia, Avgda Diagonal s/n, Barcelona, 08028, Spain

    J. Muñoz, X. Barril & F. J. Luque

  2. Departament de Bioquímica i Biologia Molecular, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1, Barcelona, 08028, Spain

    J. L. Gelpí & M. Orozco

Authors
  1. J. Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. X. Barril
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. J. Luque
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. L. Gelpí
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Orozco
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Girona, Girona, Catalonia, Spain

    Ramon Carbó-Dorca  & Xavier Gironés  & 

  2. University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    Paul G. Mezey

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Science+Business Media New York

About this chapter

Cite this chapter

Muñoz, J., Barril, X., Luque, F.J., Gelpí, J.L., Orozco, M. (2001). Partitioning of Free Energies of Solvation into Fragment Contributions: Applications in Drug Design. In: Carbó-Dorca, R., Gironés, X., Mezey, P.G. (eds) Fundamentals of Molecular Similarity. Mathematical and Computational Chemistry. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-3273-3_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-3273-3_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-3344-7

  • Online ISBN: 978-1-4757-3273-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation