Synthesis and biological activity of KCB-328 and its analogues: novel class III antiarrhythmic agents with little reverse frequency dependence.
A series of 3,4-dimethoxyphenethylamine derivatives was prepared, and their prolongation effects on effective refractory period of contractile response (ERPc) and action potential duration (APD) in isolated guinea-pig papillary muscles at 1 Hz and 3 Hz were examined. SAR studies led to the identification of KCB-328 (51) which is a novel class III antiarrhythmic agent with little reverse frequency dependence.
Kim
D I
DI
C&C Research Laboratories, Kyunggi-do, Korea.
Kim
H Y
HY
Kwon
L S
LS
Park
S D
SD
Jeon
G H
GH
Jung
K Y
KY
Min
J K
JK
Nam
W H
WH
Lee
K
K
Chung
Y S
YS
Tanabe
S
S
Kozono
T
T
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010627:Phenethylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*