Structure-activity relationships for prazosin and WB 4101 analogues as alpha 1-adrenoreceptor antagonists

J Med Chem. 1985 Sep;28(9):1354-7. doi: 10.1021/jm00147a042.

Abstract

Several alpha-adrenoreceptor antagonists were prepared by coupling one of the two moieties of WB 4101 (1) with one of the two moieties of prazosin (2). Their blocking activity and relative selectivity on alpha 1- and alpha 2-adrenoreceptors were evaluated in the isolated rat vas deferens. Although retaining a significant selectivity toward alpha 1-adrenoreceptors, all the drugs were weaker antagonists than the parent compounds 1 and 2. Opening the piperazine ring of 2 gave 3, which displayed a very high activity and selectivity toward alpha 1-adrenoreceptors (alpha 1/alpha 2 = 3890). This may have relevance in understanding the mode of action of prazosin. In addition, 3 may represent a valuable tool in the characterization of alpha-adrenoreceptor subtypes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / chemical synthesis*
  • Animals
  • Chemical Phenomena
  • Chemistry
  • Dioxanes / pharmacology*
  • Dioxins / pharmacology*
  • Male
  • Methylation
  • Prazosin / analogs & derivatives
  • Prazosin / pharmacology*
  • Quinazolines / pharmacology*
  • Rats
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / physiology
  • Structure-Activity Relationship
  • Vas Deferens / physiology

Substances

  • Adrenergic alpha-Antagonists
  • Dioxanes
  • Dioxins
  • Quinazolines
  • Receptors, Adrenergic, alpha
  • (2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
  • Prazosin