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Structure–activity relationships of cannabinoids: A joint CoMFA and pseudoreceptor modelling study

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Abstract

A cannabinoid pseudoreceptor model for the CB1-receptor has been constructed for 31 cannabinoids using the molecular modelling software YAK. Additionally, two CoMFA studies were performed on these ligands, the first of which was conducted prior to the building of the pseudoreceptor. Its pharmacophore is identical with the initial superposition of ligands used for pseudoreceptor construction. In contrast, the ligand alignment for the second CoMFA study was taken directly from the final cannabinoid pseudoreceptor model. This altered alignment gives markedly improved cross-validated r2 values as compared to those obtained from the original alignment with\({\text{r}}_{{\text{cross}}}^2 \) values of 0.79 and 0.63, respectively, for five components. However, the pharmacophore alignment has the better predictive ability. Both the CoMFA and pseudoreceptor methods predict the free energy of binding of test ligands well.

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Authors and Affiliations

  1. Institute of Pharmacy, University of Tübingen, Auf der Morgenstelle 8, D-72076, Tübingen, Germany

    Silke Schmetzer, Karl-Artur Kovar & Meike Schulze-Alexandru

  2. Department of Pharmacy, ETH Zürich, CH-8057, Zürich, Switzerland

    Paulette Greenidge & Gerd Folkers

Authors
  1. Silke Schmetzer
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  2. Paulette Greenidge
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  3. Karl-Artur Kovar
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  4. Meike Schulze-Alexandru
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  5. Gerd Folkers
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Schmetzer, S., Greenidge, P., Kovar, KA. et al. Structure–activity relationships of cannabinoids: A joint CoMFA and pseudoreceptor modelling study. J Comput Aided Mol Des 11, 278–292 (1997). https://doi.org/10.1023/A:1007960712989

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