Skip to main content
SpringerLink
Log in

Investigation of substituent effect of 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides on CCR5 binding affinity using QSAR and virtual screening techniques

  • Published:
Journal of Computer-Aided Molecular Design Aims and scope Submit manuscript

Summary

A linear quantitative–structure activity relationship model is developed in this work using Multiple Linear Regression Analysis as applied to a series of 51 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides derivatives with CCR5 binding affinity. For the selection of the best variables the Elimination Selection-Stepwise Regression Method (ES-SWR) is utilized. The predictive ability of the model is evaluated against a set of 13 compounds. Based on the produced QSAR model and an analysis on the domain of its applicability, the effects of various structural modifications on biological activity are investigated. The study leads to a number of guanidine derivatives with significantly improved predicted activities.

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. Burrows J.N., Cumming J.G., Fillery S.M., Hamlin G.A., Hudson J.A., Jackson R.J., McLaughlin S., Shaw J.S., (2005) Bioorg. Med. Chem. Lett. 15: 25

    Article  CAS  Google Scholar 

  2. Kazmierski W., Bifoulco N., Yang H., Boone L., DeAnda F., Watson C., Kenakin T., (2003) Bioorg. Med. Chem. 11: 2663

    Article  CAS  Google Scholar 

  3. Pipitone N., Pitzalis C., (2000) Curr. Opin. Anti-inflammat. Immunomodulat. Invset. Drugs 2: 9

    CAS  Google Scholar 

  4. Sellebjerg F., Madsen H.O., Jensen C.V., Jensen J., Garred P.J, (2000) J. Neuroimmunol. 102: 98

    Article  CAS  Google Scholar 

  5. Fischereder M., Luckow B., Wuthrich R.P., Rothenpieler U., Schneeberger H., Panzer U., Stahl R.A.K., Hauser I.A, Budde K., Neumayer H.-H., Kramer B.K., Land W., Schlondorff D., (2001) Lancet 387: 1758

    Article  Google Scholar 

  6. Andres P.G., Beck P.L., Mizoguchi E., Mizoguchi A., Bhan A.K., Dawson T., Kuziel W.A., Maeda N., MacDermott N., Podolsky R.P, Reinecker D.K., (2000) J. Immunol. 164: 6303

    CAS  Google Scholar 

  7. Debnath A.K., (2003) J. Med. Chem. 46: 4501

    Article  CAS  Google Scholar 

  8. Xu Y., Liu H., Niu C., Luo C., Shen J., Chen K., Jiang H., (2004) Bioorg. Med. Chem. 12: 6193

    Article  CAS  Google Scholar 

  9. Song M., Breneman C.M., Sukumar N., (2004) Bioorg. Med. Chem. 12: 489

    Article  CAS  Google Scholar 

  10. Leonard J.T., Roy K., (2004) QSAR Comb. Sci. 23: 387

    Article  CAS  Google Scholar 

  11. Roy K., Leonard J.T., (2005) J. Chem. Inf. Model. 45: 1352

    Article  CAS  Google Scholar 

  12. Todeschini, R., Consonni, V., Mannhold, R. (Series Editor), Kubinyi, H. (Series Editor) and Timmerman, H. (Series Editor), Handbook of Molecular Descriptors, Wiley-VCH, Weinheim, 2000

  13. Efroymson, M.A., In Ralston, A. and Wilf, H.S. (Eds.), Mathematical Methods for Digital Computers, Wiley, NY, 1960

  14. Efron B., (1983) J. Am. Stat. Assoc., 78: 316

    Article  Google Scholar 

  15. Osten D.W., (1998) J. Chemom. 2: 39

    Article  Google Scholar 

  16. Wold, S. and Eriksson, L., In Van de Waterbeemd, H. (Ed.), Chemometrics Methods In Molecular Design, VCH Weinheim, Germany, 1995

  17. Tropsha A., Gramatica P., Gombar V.K., (2003) QSAR Comb. Sci. 22: 1

    Article  Google Scholar 

  18. Golbraikh A., Tropsha A., (2002) J. Mol. Graph. Mod. 20: 269

    Article  CAS  Google Scholar 

  19. Shen M., Beguin C., Golbraikh A., Stables J., Kohn H., Tropsha A., (2004) J. Med. Chem. 47: 2356

    Article  CAS  Google Scholar 

  20. Atkinson A. 1985. Plots, Transformations and Regression. Clarendon Press, Oxford (UK)

    Google Scholar 

  21. Walters W.P.A., Murcko M.A., (1999) Curr. Opin. Chem. Biol. 3: 384

    Article  CAS  Google Scholar 

  22. Devillers, J. (Ed.), Comparative QSAR. Taylor and Francis, Washington, DC, 1998

  23. Hansch C., Leo A., 1995. Exploring QSAR: Fundamentals and Applications in Chemistry and Biology. ACS, Washington, DC

    Google Scholar 

  24. Melagraki G., Afantitis A., Sarimveis H., Igglessi-Markopoulou O., Supuran C.T, (2006). Bioorg. Med. Chem. 14: 1108

    Article  CAS  Google Scholar 

  25. Melagraki, G., Afantitis, Α., Sarimveis, H., Igglessi-Markopoulou, O. and Alexandridis, A., Mol. Div. (2006) In Press ID AP_11030_2005_9008

  26. Golbraikh A., Tropsha A., (2000) Mol. Div. 5: 231

    Article  CAS  Google Scholar 

  27. Aptula A.O., Jeliazkova N.G., Schultz T.W., Cronin M.T.D., (2005) QSAR Comb. Sci. 24: 385

    Article  CAS  Google Scholar 

  28. Afantitis, Α., Melagraki, G., Sarimveis, H., Koutentis, P.A., Markopoulos, J. and Igglessi-Markopoulou, O., Mol. Div. (2006) In Press DOI MODI28R2

Download references

Acknowledgements

A.A. wishes to thank Cyprus Research Promotion Foundation (Grant No. PENEK/ENISX/0603/05) for its financial support. A.A and G.M. whish to thank Leventis Foundation for its financial support.

Author information

Authors and Affiliations

  1. School of Chemical Engineering, National Technical University of Athens, Athens, Greece

    Antreas Afantitis, Georgia Melagraki, Haralambos Sarimveis & Olga Igglessi-Markopoulou

  2. Department of ChemoInformatics, NovaMechanics Ltd, Larnaca, Cyprus

    Antreas Afantitis

  3. Department of Chemistry, University of Cyprus, P.O. Box 20537, 1678, Nicosia, Cyprus

    Panayiotis A. Koutentis

  4. Department of Chemistry, University of Athens, Athens, Greece

    John Markopoulos

Authors
  1. Antreas Afantitis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Georgia Melagraki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haralambos Sarimveis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Panayiotis A. Koutentis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John Markopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Olga Igglessi-Markopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Haralambos Sarimveis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Afantitis, A., Melagraki, G., Sarimveis, H. et al. Investigation of substituent effect of 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides on CCR5 binding affinity using QSAR and virtual screening techniques. J Comput Aided Mol Des 20, 83–95 (2006). https://doi.org/10.1007/s10822-006-9038-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10822-006-9038-2

Keywords

Search

Navigation