Skip to main content
SpringerLink
Log in

Bioisosteric equivalence of five-membered heterocycles

  • Published:
Chemistry of Heterocyclic Compounds Aims and scope

A variety of factors can affect bioisosteric relationships between structural motifs in a medicinal chemistry optimization project, both in terms of ligand affinity to a given target and off-target profile. Such parameters, e.g. the ability to participate in hydrogen bonding and π–π interactions, basicity, and solubility are discussed with a particular focus on five-membered heterocycles and their application in drug design.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Notes

  1. V. Y. Dudkin, K. Rickert, C. Kreatsoulas, C. Wang, K. Arrington, M. E. Fraley, G. D. Hartman, Y. Yan, M. Ikuta, S. Stirdivant, R. A. Drakas, E. S. Walsh, K. Hamilton, C. Buser, R. B. Lobell, L. Sepp-Lorenzino, Bioorg. Med. Chem. Lett., in press.

References

  1. C. G. Wermuth, The Practice of Medicinal Chemistry, Academic Press, London, 1996.

    Google Scholar 

  2. G. A. Patani and E. J. LaVoie, Chem. Rev., 96, 3147 (1996).

    Article  CAS  Google Scholar 

  3. H. L. Friedman, NAS-NRS Publication No. 206, Washington (1951), p. 295.

  4. C. F. Matta, A. A. Arabi, and D. F. Weaver, Eur. J. Med. Chem, 45, 1868 (2010).

    Article  CAS  Google Scholar 

  5. S. R. Langdon, P. Ertl, and N. Brown, Mol. Inf., 29, 366 (2010).

    Article  CAS  Google Scholar 

  6. N. A. Meanwell, J. Med. Chem., 54, 2529 (2011).

    Article  CAS  Google Scholar 

  7. C. Laurence and M. Berthelot, Perspect. Drug Discovery Des., 18, 39 (2000).

    Article  CAS  Google Scholar 

  8. M. H. Abraham, P. P. Duce, D. V. Prior, D. G. Barratt, J. J. Morris, and P. J. Taylor, J. Chem. Soc., Perkin Trans. 2, 1355 (1989).

  9. M. H. Abraham, P. L. Grellier, D. V. Prior, P. P. Duce, J. J. Morris, and P. J. Taylor, J. Chem. Soc., Perkin Trans. 2, 699 (1989).

  10. C. Laurence, K. A. Brameld, J. Graton, J.-Y. Le Questel, and E. Renault. J. Med. Chem., 52 4073 (2009).

    Article  CAS  Google Scholar 

  11. A. C. Pierce, K. L. Sandretto, and G. W. Bemis, Proteins: Struct., Funct., Genet., 49, 567 (2002).

    Article  CAS  Google Scholar 

  12. S. Ioannidis, M. L. Lamb, A. M. Davies, L. Almeida, M. Su, G. Bebernitz, M. Ye, K. Bell, M. Alimzhanov, and M. Zinda, Bioorg. Med. Chem. Lett., 19, 6524 (2009).

    Article  CAS  Google Scholar 

  13. A. C. Pierce, E. ter Haar, H. M. Binch, D. P. Kay, S. R. Patel, and P. Li, J. Med. Chem., 48, 1278 (2005).

    Article  CAS  Google Scholar 

  14. M. L. Lolli, C. Giordano, D. S. Pickering, B. Rolando, K. B. Hansen, A. Foti, A. Contreras-Sanz, A. Amir, R. Fruttero, A. Gasco, B. Nielsen, and T. N. Johansen, J. Med. Chem., 53, 4110 (2010).

    Article  CAS  Google Scholar 

  15. M. T. Bilodeau, A. E. Balitza, T. J. Koester, P. J. Manley, L. D. Rodman, C. Buser-Doepner, K. E. Coll, C. Fernandes, J. B. Gibbs, D. C. Heimbrook, W. R. Huckle, N. Kohl, J. J. Lynch, X. Mao, R. C. McFall, D. McLoughlin, C. M. Miller-Stein, K. W. Rickert, L. Sepp-Lorenzino, J. M. Shipman, R. Subramanian, K. A. Thomas, B. K. Wong, S. Yu, and G. D. Hartman, J. Med. Chem., 47, 6363 (2004).

    Article  CAS  Google Scholar 

  16. M. T. Bilodeau, L. D. Rodman, G. B. McGaughey, K. E. Coll, T. J. Koester, W. F. Hoffman, R. W. Hungate, R. L. Kendall, R. C. McFall, K. W. Rickert, R. Z. Rutledge, and K. A. Thomas, Bioorg. Med. Chem. Lett., 14, 2941 (2004).

    Article  CAS  Google Scholar 

  17. J. T. Sisko, T. J. Tucker, M. T. Bilodeau, C. A. Buser, P. A. Ciecko, K. E. Coll, C. Fernandes, J. B. Gibbs, T. J. Koester, N. Kohl, J. J. Lynch, X. Mao, D. McLoughlin, C. M. Miller-Stein, L. D. Rodman, K. W. Rickert, L. Sepp-Lorenzino, J. M. Shipman, K. A. Thomas, B. K. Wong, and G. D. Hartman, Bioorg. Med. Chem. Lett., 16, 1146 (2006).

    Article  CAS  Google Scholar 

  18. S. Ioannidis, M. L. Lamb, L. Almeida, H. Guan, B. Peng, G. Bebernitz, K. Bell, M. Alimzhanov, and M. Zinda, Bioorg. Med. Chem. Lett., 20, 1669 (2010).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA, 18486, USA

    V. Y. Dudkin

Authors
  1. V. Y. Dudkin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. Y. Dudkin.

Additional information

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 32-37, January, 2012.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dudkin, V.Y. Bioisosteric equivalence of five-membered heterocycles. Chem Heterocycl Comp 48, 27–32 (2012). https://doi.org/10.1007/s10593-012-0964-8

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10593-012-0964-8

Keywords

Search

Navigation