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Quantitative structure – activity relationship studies on membrane receptors inhibition by antipsychotic drugs. Application to schizophrenia treatment

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Abstract

There are presented six new QSAR models, which are correlating antipsychotic activity (pK i values at dopamine D1–D4 and serotonine (5-HT2C, 5-HT2A) receptors) with physicochemical parameters. A large data set of typical and atypical antipsychotics already approved for clinical treatment including as well representatives with new chemical structures which are exhibiting antipsychotic activity (tetrahydrofuran-, benzamide-, 3-aminoethyl-1-tetralones-, piperazine-, benzothiazepine- and pyrrolobenzazepine-derivatives) were incorporated within this study. The appropriate 2D and internal-3D molecular descriptors could be generated by use of the computational software MOE (Molecular Operating Environment). Significant q 2 (0.63–0.76) and r 2 (0.70–0.78) correlation coefficients were obtained, indicating that the established equations can be used within a wide range of binding constants (pK i = 5 to 9.76). By use of these linear models an assembly of new aripiprazole structures could be established. Some of them are showing significantly improved antipsychotic activity in comparison with the parent compound.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucharest, Romania

    Speranta Avram

  2. Pharmaceutical Chemistry, University of Vienna, Vienna, Austria

    Heinz Berner

  3. Institute of Biochemistry of the Romanian Academy, Bucharest, Romania

    Adina L. Milac

  4. Institute for Theoretical Chemistry, University of Vienna, Vienna, Austria

    Peter Wolschann

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  1. Speranta Avram
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  2. Heinz Berner
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  3. Adina L. Milac
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  4. Peter Wolschann
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Correspondence to Speranta Avram.

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Correspondence: Speranta Avram, Department of Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 76201 Bucharest, Romania.

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Avram, S., Berner, H., Milac, A. et al. Quantitative structure – activity relationship studies on membrane receptors inhibition by antipsychotic drugs. Application to schizophrenia treatment. Monatsh Chem 139, 407–426 (2008). https://doi.org/10.1007/s00706-007-0782-3

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