beta-Adrenergic blocking agents with acute antihypertensive activity

J Med Chem. 1979 Jun;22(6):687-94. doi: 10.1021/jm00192a015.

Abstract

Modification of the pharmacological profile of the vasodilating/beta-adrenergic blocking agent 2-[4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-4-(trifluoromethyl)imidazole (1) has been investigated. Introduction of selected substitutents onto the imidazole ring, in place of the trifluoromethyl group, has yielded highly cardioselective beta-adrenergic blocking agents such as 7, 17, and 18. The placement of alkyl or chloro groups onto the aryl ring of 1, as illustrated by 33, has produced a class of compounds characterized as antihypertensive beta-adrenergic blocking agents. In these examples, the acute antihypertensive activity does not appear to be due to either vasodilating or beta 2-agonist properties.

MeSH terms

  • Adrenergic beta-Antagonists / chemical synthesis*
  • Airway Resistance / drug effects
  • Animals
  • Antihypertensive Agents / chemical synthesis*
  • Blood Pressure / drug effects
  • Dogs
  • Female
  • Heart / drug effects
  • Heart Rate / drug effects
  • Hypertension / physiopathology
  • Iliac Artery
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology
  • Male
  • Organ Specificity
  • Rats
  • Regional Blood Flow / drug effects
  • Structure-Activity Relationship

Substances

  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Imidazoles