title: Structure-activity relationships in 1,4-benzodioxan-related compounds. Investigation on the role of the dehydrodioxane ring on alpha 1-adrenoreceptor blocking activity.
abstract: Several analogues of 2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzodioxa n (WB 4101, 1) were prepared and evaluated for their blocking activity on alpha 1- and alpha 2-adrenoreceptors in the isolated rat vas deferens. The results were compared with those obtained for 1 and benoxathian (2). It was shown that the two oxygens at positions 1 and 4 may have a different role in receptor binding. It seems that the oxygen at position 4 as such does not contribute to the binding while it is important in stabilizing an optimal conformation for drug-receptor interaction mechanism. On the other hand, the oxygen at position 1 might interact with a receptor polar pocket of reduced size by way of a donor-acceptor dipolar interaction. Furthermore, it was shown that replacement of the dehydrodioxane ring of 1 by a phenyl or a pyrrole nucleus causes a significant decrease in activity.
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000138:chemical synthesis* / Q000494:pharmacology; D004147:Dioxins / Q000138:chemical synthesis*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010075:Oxathiins / Q000494:pharmacology; D010100:Oxygen; D051381:Rats; D013329:Structure-Activity Relationship; D013455:Sulfur; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004147:Dioxins; D010075:Oxathiins; D013455:Sulfur; C050877:benoxathian; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D010100:Oxygen; D009638:Norepinephrine