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Molecular modelling and conformational analysis of a GABAB antagonist

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Summary

Crystallographic database studies and molecular dynamics simulations in different media have enabled us to sample the conformational space of a GABAB antagonist. As a result, we have defined a pharmacophoric pattern for GABAB antagonists. This study has led us to compare the conformational preferences deduced from database studies and molecular dynamics simulations. The influence of the medium on the conformations has also been investigated.

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References

  1. Krogsgaard-Larsen, P., Frølund, B., Jørgensen, F.S. and Schousboe, A., J. Med. Chem., 37 (1994) 2489.

    Google Scholar 

  2. Bowery, N.G., Annu. Rev. Pharmacol. Toxicol., 33 (1993) 109.

    Google Scholar 

  3. Chapman, R.W., Hey, J.A., Rizzo, C.A. and Bolser, D.C., Trends Pharmacol. Sci., 14 (1993) 26.

    Google Scholar 

  4. Bittiger, H., Froestl, W., Mickel, S.J. and Olpe, H.R., Trends Pharmacol. Sci., 14 (1993) 391.

    Google Scholar 

  5. Berthelot, P., Vaccher, C., Musadad, A., Flouquet, N., Debaert, M. and Luyckx, M., J. Med. Chem., 30 (1987) 743.

    Google Scholar 

  6. Berthelot, P., Vaccher, C., Flouquet, N., Debaert, M., Luyckx, M. and Brunet, C., J. Med. Chem., 34 (1991) 2557.

    Google Scholar 

  7. Hammond, D.L. and Moy, M.L., Eur. J. Pharmacol., 229 (1992) 227.

    Google Scholar 

  8. Kerr, D.I.B., Ong, J., Johnston, G.A.R., Berthelot, P., Debaert, M. and Vaccher, C., Eur. J. Pharmacol., 164 (1989) 361.

    Google Scholar 

  9. Ong, J., Kerr, D.I.B., Berthelot, P., Vaccher, C., Flouquet, N. and Debaert, M., Eur. J. Pharmacol., 221 (1992) 145.

    Google Scholar 

  10. Pirard, B., Paquet, B., Evrard, G., Berthelot, P., Vaccher, C., Ansard, M.H., Debaert, M. and Durant, F., Eur. J. Med. Chem., 30 (1995) 851.

    Google Scholar 

  11. Froestl, W., Mickel, S.J., Von, Sprecher, G., Bittiger, H. and Olpe, H.R., Pharmacol. Commun., 2 (1992) 52.

    Google Scholar 

  12. Leach, A.R., In Lipkowitz, K.B. and Boyd, D.B. (Eds.) Reviews in Computational Chemistry, Vol. 2, VCH, New York, NY, 1991, pp. 1–55.

    Google Scholar 

  13. Allen, F.H. and Kennard, O., CDA News, 8 (1993) 31.

    Google Scholar 

  14. Allen, F.H., Johnson, O., Macrae, C.F., Smith, M.J., Motherwell, S.W.D., Galloy, J.J., Watson, D.G., Rowland, R.S., Edgington, P.R., Garner, S.E., Davies, J.E. and Mitchell, G.F., CSD System, Vol. 1, Cambridge Crystallographic Data Centre, Cambridge, 1992, pp. 639–645.

    Google Scholar 

  15. Willett, P., In Dean, P.M. (Ed.) Molecular Similarity in Drug Design, Blackie Academic & Professional, London, 1995, pp. 110–132.

    Google Scholar 

  16. Willett, P., Winterman, V. and Bawden, D., J. Chem. Inf. Comput. Sci., 26 (1986) 36.

    Google Scholar 

  17. Vanderveken, D.J. and Vercauteren, D.P., ZEDIT, Facultés Universitaires Notre-Dame de la Paix, Namur, 1992.

    Google Scholar 

  18. Auffinger, P. and Wipff, G., J. Comput. Chem., 11 (1990) 19.

    Google Scholar 

  19. Rekker, R.F. and Mannhold, R., Calculation of Drug Lipophilicity: The hydrophobic Fragmental Constant Approach, VCH, Weinheim, 1992.

    Google Scholar 

  20. DISCOVER, v. 2.9.5/94.0, Biosym Technologies, San Diego, CA, 1994.

  21. DISCOVER, v. 2.9.5/94.0, User Guide, Part 1, Biosym Technologies, San Diego, CA, 1994, pp 3.1–3.32.

  22. Maple, J.R., Hwang, M.-J., Stockfisch, T.P., Dinur, U., Waldman, M., Ewig, C.S. and Hagler, A.T., J. Comput. Chem., 15 (1994) 162.

    Google Scholar 

  23. Maple, J.R., Dinur, U. and Hagler, T., Proc. Natl. Acad. Sci. USA, 85 (1988) 5350.

    Google Scholar 

  24. Perez, J.J., Villar, H.O. and Loew, G.H., J. Comput.-Aided Mol. Design, 6 (1992) 175.

    Google Scholar 

  25. INSIGHT II, v. 2.3.0, Biosym Technologies, San Diego, CA, 1993.

  26. Coluci, W.J., Gandour, R.D. and Mooberry, E.A., J. Am. Chem. Soc., 108 (1986) 7147.

    Google Scholar 

  27. Vaccher, C., Berthelot, P., Flouquet, N., Marko, J. and Debaert, M., Spectrochim. Acta, 47 (1991) 1071.

    Google Scholar 

  28. Vaccher, C., Berthelot, P., Debaert, M., Vermeersch, G., Guyon, R., Pirard, B., Vercauteren, D.P., Dory, M., Evrard, G. and Durant, F., J. Mol. Struct., 301 (1993) 199.

    Google Scholar 

  29. Böhm, H.J., Klebe, G., Lorenz, T., Mietzner, T. and Siggel, L., J. Comput. Chem., 11 (1990) 1021.

    Google Scholar 

  30. Falch, E., Hedegaard, A., Nielsen, L., Jensen, B.R., Hjeds, H. and Krogsgaard-Larsen, P., J. Neurochem., 47 (1986) 898.

    Google Scholar 

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Authors and Affiliations

  1. Laboratoire de Chimie Moléculaire Structurale, Facultés Universitaires Notre-Dame de la Paix, rue de Bruxelles 61, B-5000, Namur, Belgium

    Bernard Pirard & François Durant

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  1. Bernard Pirard
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  2. François Durant
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Pirard, B., Durant, F. Molecular modelling and conformational analysis of a GABAB antagonist. J Computer-Aided Mol Des 10, 31–40 (1996). https://doi.org/10.1007/BF00124463

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