Structure-activity relationship of a novel K+ channel opener, KRN4884, and related compounds in porcine coronary artery

Gen Pharmacol. 1996 Sep;27(6):985-9. doi: 10.1016/0306-3623(95)02139-6.

Abstract

1. KRN4884 (5-amino-N-[2-(2-chlorophenyl) ethyl]-N'-cyano-3-pyridinecarboxamidine), Ki3005 (5-deamino KRN4884), Ki5624 (2-dechloro KRN4884) and Ki1769 (5-deamino-2-dechloro KRN4884) produced concentration-dependent relaxations in isolated porcine coronary arteries contracted by 25 mM KC1. The order of relaxant potency was KRN4884 > Ki3005 > Ki5624 > Ki1769. 2. The relaxation induced by these compounds was antagonized by glibenclamide; they had almost no effect on coronary arteries contracted by 60 mM KC1. 3. The present results suggest that these pyridinecarboxamidine derivatives have vasodilating ability based on a K+ channel opening action, and that both the amino groups in the pyridine nucleus and the chlorine atom in the benzene nucleus in pyridinecarboxamidine are important for their potency as a K+ channel opener.

MeSH terms

  • Animals
  • Coronary Vessels / drug effects*
  • Coronary Vessels / physiology
  • Dose-Response Relationship, Drug
  • Glyburide / pharmacology
  • Potassium Channels / drug effects*
  • Pyridines / pharmacology*
  • Structure-Activity Relationship
  • Swine
  • Vasodilator Agents / pharmacology*

Substances

  • KRN 4884
  • Potassium Channels
  • Pyridines
  • Vasodilator Agents
  • Glyburide