Synthesis and antiarrhythmic activity of disubstituted phenylpyridine derivative.
A series of disubstituted phenylpyridine derivatives was synthesized and their antiarrhythmic effects against chloroform-induced ventricular arrhythmias in mice were examined. Among them, 2- and 3-[2-(3-aminobutyramido)-4-(2,2,2-trifluroethoxy)phenyl]pyri dines (23h, 24h) and 3-[2-(3-aminobutyramido)-4-ethoxyphenyl]pyridine (24i) showed potent antiarrhythmic activity. They had approximately twice the potency of mexiletine (III). Compound 24i was selected from this series as a candidate for further development; it was found to have a class I B electrophysiological character and to show a slow kinetic rate-dependent block (RDB) of the sodium channel in cardiac muscle.
Shigyo
H
H
Tokyo Research Laboratories, Kowa Co., Ltd., Japan.
Sato
S
S
Shibuya
K
K
Takahashi
Y
Y
Yamaguchi
T
T
Sonoki
H
H
Ohta
T
T
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D051379:Mice; D008813:Mice, Inbred ICR; D010210:Papillary Muscles / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000517:prevention & control
D000889:Anti-Arrhythmia Agents; D011725:Pyridines