A series of novel openphendioxan analogues were synthesized and tested at α1-adrenoreceptor (AR) subtypes by binding and functional assays. The α1d-AR binding profile was also examined by means of 2D, 3D-QSAR together with docking studies. Multiple regression analysis suggested the relevance of adequate number of heteroatoms in the whole molecule and of passive membrane diffusion to enhance α1d-AR affinity. Docking simulations against a computational structural model of the biological target further proved this evidence and furnished support for chemiometric analysis, where polar, electrostatic, hydrophobic and shape effects of the ortho substituents in the phenoxy terminal, most likely governing ligand binding, helped the depiction of pharmacophore hypothesis for the examined ligands data set.
Structure-activity relationships in 1,4-benzodioxan-related compounds. 10. Novel alpha1-adrenoreceptor antagonists related to openphendioxan: synthesis, biological evaluation, and alpha1d computational study
PIERGENTILI, Alessandro;DEL BELLO, FABIO;GIANNELLA, Mario;PIGINI, Maria;QUAGLIA, Wilma
2010-01-01
Abstract
A series of novel openphendioxan analogues were synthesized and tested at α1-adrenoreceptor (AR) subtypes by binding and functional assays. The α1d-AR binding profile was also examined by means of 2D, 3D-QSAR together with docking studies. Multiple regression analysis suggested the relevance of adequate number of heteroatoms in the whole molecule and of passive membrane diffusion to enhance α1d-AR affinity. Docking simulations against a computational structural model of the biological target further proved this evidence and furnished support for chemiometric analysis, where polar, electrostatic, hydrophobic and shape effects of the ortho substituents in the phenoxy terminal, most likely governing ligand binding, helped the depiction of pharmacophore hypothesis for the examined ligands data set.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
