3D-QSAR CoMFA study of benzoxazepine derivatives as mGluR5 positive allosteric modulators

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5922-4. doi: 10.1016/j.bmcl.2010.07.061. Epub 2010 Jul 30.

Abstract

Positive allosteric modulation of the metabotropic glutamate receptor subtype 5 was studied by conducting a comparative molecular field analysis on 118 benzoxazepine derivatives. The model with the best predictive ability retained significant cross-validated correlation coefficients of q(2) = 0.58 (r(2) = 0.81) yielding a standard error of 0.20 in pEC(50) for this class of compounds. The subsequent contour maps highlight the structural features pertinent to the bioactivity values of benzoxazepines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Allosteric Regulation
  • Benzoxazines / chemical synthesis
  • Benzoxazines / chemistry*
  • Benzoxazines / pharmacology
  • Drug Design
  • Models, Chemical
  • Models, Molecular
  • Quantitative Structure-Activity Relationship
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / chemistry*
  • Receptors, Metabotropic Glutamate / metabolism
  • Static Electricity

Substances

  • Benzoxazines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate