Structure-activity relationships in 1,4-benzodioxan-related compounds. 5. Effects of modification of the side chain on alpha-adrenoreceptor blocking activity

Farmaco. 1996 Jan;51(1):27-32.

Abstract

The observation that the insertion of a phenyl ring at position 3 of WB 4101 (1) afforded a potent and selective alpha 1-adrenoreceptor antagonist, phendioxan (2), prompted us to investigate the effect on alpha-adrenoreceptor blocking activity of replacing a hydrogen atom at the 2-position or on the 2-ylmethyl moiety of 1 and 2 by a methyl, ethyl or phenyl group. Thus compounds 3-11 were synthesized and their blocking activity and relative selectivity on alpha 1- and alpha 2-adrenoreceptors were evaluated in the isolated rat vas deferens in comparison to 1 and 2. The results of such investigation showed that this structural modification caused a decrease in affinity for alpha-adrenoreceptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Antagonists / chemical synthesis*
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Dioxanes / chemistry
  • Dioxanes / pharmacology
  • In Vitro Techniques
  • Male
  • Muscle, Smooth / drug effects
  • Rats
  • Structure-Activity Relationship
  • Vas Deferens / drug effects

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Antagonists
  • Dioxanes
  • (2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane