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Using a pharmacophore representation concept to elucidate molecular similarity of dopamine antagonists

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Abstract

The pharmacophoric concept plays an important role in ligand-based drug design methods to describe the similarity and diversity of molecules, and could also be exploited as a molecular representation scheme. A three-point pharmacophore method was used as a molecular representation perception. This procedure was implemented for dopamine antagonists of the D2 receptor subtype. The molecular structures of the antagonists included in this analysis were categorized into two structurally distinct classes. Using structural superposition with internal energy minimization, two pharmacophore models were deduced. Based on these two models other D2 antagonists that fulfil them were derived and studied. This procedure aided the identification of the common 3D patterns present in diverse molecules that act at the same biological target and the extraction of a common molecular framework for the two structural classes. The pharmacophoric information was found to be suitable for guiding superposition of structurally diverse molecules, using a more biologically meaningful selection of the targeting points.

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Acknowledgement

The authors would like to gratefully acknowledge Professor Stavros Hamodrakas for his advices and help.

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Authors and Affiliations

  1. Biomedical Informatics Unit, Foundation for Biomedical Research of the Academy of Athens, Soranou Efesiou 4, 11527, Athens, Greece

    V. Atlamazoglou & T. Thireou

  2. Institute of Computer Science, Foundation for Research and Technology Hellas, Heraklion, Crete, Greece

    T. Thireou

  3. Laboratory of Genetics, Agricultural University of Athens, Athens, Greece

    E. Eliopoulos

Authors
  1. V. Atlamazoglou
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  2. T. Thireou
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  3. E. Eliopoulos
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Correspondence to V. Atlamazoglou.

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Atlamazoglou, V., Thireou, T. & Eliopoulos, E. Using a pharmacophore representation concept to elucidate molecular similarity of dopamine antagonists. J Comput Aided Mol Des 21, 239–249 (2007). https://doi.org/10.1007/s10822-007-9110-6

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  • DOI: https://doi.org/10.1007/s10822-007-9110-6

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