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Bioorg Med Chem. 2010 Oct 1;18(19):7065-77. doi: 10.1016/j.bmc.2010.08.002. Epub 2010 Aug 6.

Structure-activity relationships in 1,4-benzodioxan-related compounds. 10. Novel α1-adrenoreceptor antagonists related to openphendioxan: synthesis, biological evaluation, and α1d computational study.

Author information

1
Dipartimento Farmaco-Chimico, Università di Bari, via Orabona 4, 70125 Bari, Italy. carrieri@farmchim.uniba.it

Abstract

A series of novel openphendioxan analogues were synthesized and tested at α(1)-adrenoreceptor (AR) subtypes by binding and functional assays. The α(1d)-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 α(1d)-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.

PMID:
20801662
DOI:
10.1016/j.bmc.2010.08.002
[Indexed for MEDLINE]

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