Synthesis and biological activity of KCB-328 and its analogues: Novel class III antiarrhythmic agents with little reverse frequency dependence

• Published in: Bioorganic & medicinal chemistry letters Vol. 9; no. 1; pp. 85 - 90
• Main Authors: Kim, Dong-Ick, Kim, Hak-Yeop, Kwon, Lae-Sung, Park, Sung-Dae, Jeon, Gee-Ho, Jung, Kyung-Yun, Min, Jae-Ki, Nam, Woong-Hyun, Lee, Kiho, Chung, You-Sup, Tanabe, Shigeru, Kozono, Toshiro
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 04-01-1999; Elsevier
• Subjects: Animals; Anti-Arrhythmia Agents - chemical synthesis; Anti-Arrhythmia Agents - chemistry; Anti-Arrhythmia Agents - pharmacology; Antiarrhythmic agent; Antiarythmic agents; Biological and medical sciences; Cardiovascular activity; Cardiovascular system; Drug Evaluation, Preclinical; Guinea Pigs; In Vitro Techniques; Medical sciences; Muscle Contraction - drug effects; Myocardial Contraction - drug effects; Papillary Muscles - drug effects; Pharmacology. Drug treatments; Phenethylamines - chemical synthesis; Phenethylamines - chemistry; Phenethylamines - pharmacology; Potassium channel blockers; Reverse frequency dependence; Structure-Activity Relationship; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacology; Reverse frequency dependence; Cardiovascular activity; Potassium channel blockers; Antiarrhythmic agent; Sulfonamide; Papillary muscle; Rodentia; Aminoether; Action potential; In vitro; Vertebrata; Mammalia; Guinea pig; Structure activity relation; Animal; Benzenic compound; Chemical synthesis; Primary amine
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(98)00689-1

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.
A series of 3,4-dimethoxyphenethylamine derivatives was prepared, and tested for their antiarrhythmic activities at different pacing frequencies. SAR studies led to the identification of KCB-328, which showed novel class III antiarrhythmic effects with little reverse frequency dependence.