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Structure-activity relationships in 1,4-benzodioxan-related compounds. Investigation on the role of the dehydrodioxane ring on alpha 1-adrenoreceptor blocking activity.

Authors
  • Pigini, M
  • Brasili, L
  • Giannella, M
  • Giardinà, D
  • Gulini, U
  • Quaglia, W
  • Melchiorre, C
Type
Published Article
Journal
Journal of medicinal chemistry
Publication Date
Dec 01, 1988
Volume
31
Issue
12
Pages
2300–2304
Identifiers
PMID: 2903932
Source
Medline
License
Unknown

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.

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