Summary
A structure-activity study has been carried out on several compounds known as inhibitors of the serine protease prolyl endopeptidase. Conformational analysis has been done using different molecular mechanics methods such as molecular dynamics, or a randomized conformational search method. The conformers obtained were classified using geometric and energetic criteria. A pattern recognition analysis was done in order to divide conformers according to families. The resulting dominant families, for all compounds investigated, showed very similar geometric features. Based on the lowest energy conformers obtained after randomized conformational analysis, a 3D-QSAR model was established using the CoMFA approach. The validity of this model was verified by prediciting correctly the activity of other molecules not used in the construction of this model.
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Langer, T., Wermuth, C.G. Inhibitors of prolyl endopeptidase: Characterization of the pharmacophoric pattern using conformational analysis and 3D-QSAR. J Computer-Aided Mol Des 7, 253–262 (1993). https://doi.org/10.1007/BF00125501
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DOI: https://doi.org/10.1007/BF00125501