title: Molecular properties of the WB4101 enantiomers and of its chiral methyl derivatives for alpha 1-adrenoceptor recognition.
abstract: The optical isomers of the well known alpha 1-antagonist WB4101 and of its derivatives with a methyl group in the oxyethyl moiety were prepared for the evaluation of their alpha-adrenoceptors binding affinity. By means of a detailed computational analysis, the present work shows that the introduction of a methyl group affects the behaviour of WB4101 in different ways. A limitation of the conformational freedom in certain regions of the torsional subspace of the potential energy function, differences in the reactivity of the protonated species towards a model proton acceptor and the quality of the superposition with the rigid template for alpha 1 antagonists, corynanthine, are examined and discussed in order to select a candidate bioactive form and possible features which act as modulators of the recognition process at the alpha 1-adrenoceptors.
authors: Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano.
authors: L
authors: L
authors: Villa
authors: E
authors: E
authors: Valoti
authors: A M
authors: AM
authors: Villa
authors: M
authors: M
authors: Pallavicini
authors: V
authors: V
authors: Ferri
authors: E
authors: E
authors: Iuliano
authors: N
authors: N
authors: Brunello
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D001665:Binding Sites; D004146:Dioxanes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008968:Molecular Conformation; D011522:Protons; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D004146:Dioxanes; D011522:Protons; D018340:Receptors, Adrenergic, alpha-1; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane