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Synthesis and antiarrhythmic activity of alpha-[(diarylmethoxy)methyl]-1-piperidineethanols. 1991
M L Hoefle, and
L T Blouin, and
R W Fleming, and
S Hastings, and
J M Hinkley, and
T E Mertz, and
T J Steffe, and
C S Stratton, and
L M Werbel
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
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.
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