Synthesis and antiarrhythmic activity of alpha-[(diarylmethoxy)methyl]-1-piperidineethanols.
A series of alpha-[(diarylmethoxy)methyl]-1-piperidineethanols was evaluated for antiarrhythmic activity in the coronary artery ligated dog model. Structure-activity relationship studies indicated that the 2,6-dimethylpiperidine group afforded the best antiarrhythmic agents in this series and was essential for long duration of action. This investigation indicated that quaternary ammonium salts were not essential for a long duration of action. It was also shown that the antiarrhythmic activity could be separated from the tachycardia frequently caused by this type of agent.
Hoefle
M L
ML
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Blouin
L T
LT
Fleming
R W
RW
Hastings
S
S
Hinkley
J M
JM
Mertz
T E
TE
Steffe
T J
TJ
Stratton
C S
CS
Werbel
L M
LM
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis*; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000889:Anti-Arrhythmia Agents; D001593:Benzyl Compounds; D010880:Piperidines