Search for new antiarrhythmic and hypotensive compounds. Synthesis, antiarrhythmic, antihypertensive, and alpha-adrenoceptor blocking activity of novel 1-[(2-hydroxy-3-amino)]-propylpyrrolidin-2-one derivatives

Arch Pharm (Weinheim). 1997 Jul;330(7):225-31. doi: 10.1002/ardp.19973300707.

Abstract

A series of the derivatives of 1-[2-hydroxy-3-(4-phenyl-1-piperazinyl])propyl]-pyrrolidin-2- one (MG-1) was synthesized and tested for electrocardiographic, antiarrhythmic, and antihypertensive activity as well as for alpha 1- and alpha 2-adrenoceptors binding affinities. Some of the compounds of this series slightly decreased the heart rate, prolonged P-Q, Q-T intervals and QRS complex. Only compound 7 (1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-pyrrolidine) possesses potent antiarrhythmic and a slight hypotensive properties, and affinity for alpha 1- and alpha 2-adrenoceptor. The results suggest that the antiarrhythmic and hypotensive effect of compound 7 and MG-1 is related to their adrenolytic properties, and that those properties depend on the presence of a phenylpiperazine moiety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / chemical synthesis*
  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Anti-Arrhythmia Agents / chemical synthesis*
  • Anti-Arrhythmia Agents / pharmacology*
  • Antihypertensive Agents / chemical synthesis*
  • Antihypertensive Agents / pharmacology*
  • Pyrrolidinones / chemical synthesis*
  • Pyrrolidinones / pharmacology*
  • Rats
  • Structure-Activity Relationship

Substances

  • Adrenergic alpha-Antagonists
  • Anti-Arrhythmia Agents
  • Antihypertensive Agents
  • Pyrrolidinones