Document Report Card

ID: ALA1127796

Journal: J Med Chem

Title: Construction of a molecular shape analysis-three-dimensional quantitative structure-analysis relationship for an analog series of pyridobenzodiazepinone inhibitors of muscarinic 2 and 3 receptors.

Authors: Burke BJ, Dunn WJ, Hopfinger AJ.

Abstract: A generalized three-dimensional (3D) quantitative structure-property relationship (QSPR) formalism, based upon molecular shape analysis (MSA), has been applied to an analog series of pyridobenzodiazepinone inhibitors of muscarinic 2 (M2) and 3 (M3) receptors. The fundamental goal of this application is to establish MSA-3D-QSARs (P = A = inhibition activity) that are based upon identifying the active conformations of these flexible analogs. The repetitive use of partial least squares (PLS) analysis permits the construction of the MSA-3D-QSARs. In addition to molecular shape, the identification of the properties of a lipophilic binding site and specific nonallowed steric receptor sites govern the MSA-3D-QSARs. The M2 and M3 QSARs suggest receptor subtype specificity might be realized by targeting upon a specific nonallowed steric receptor site. One conformation, common to both M2 and M3 receptors, emerges as dominant in the optimum MSA-3D-QSARs. However, other similar conformations are also found to yield meaningful MSA-3D-QSARs.

CiteXplore: 7966137

DOI: 10.1021/jm00048a014