Structure-activity relationship of a novel K+ channel opener, KRN4884, and related compounds in porcine coronary artery.
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.
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
H
H
Izumi
Y
Y
Tanaka
Y
Y
Okada
N
N
Ogawa
T
T
Izawa
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*
C096484:KRN 4884; D015221:Potassium Channels; D011725:Pyridines; D014665:Vasodilator Agents; D005905:Glyburide