STRUCTURE-ACTIVITY RELATIONSHIP OF A NOVEL K-COMPOUNDS IN PORCINE CORONARY-ARTERY( CHANNEL OPENER, KRN4884, AND RELATED)

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