The synthesis of the title
ketone has been completed via a type of Mannich reaction starting from 4- thianone . An X-ray diffraction analysis has revealed that the solid system is a chair-boat conformer with the
sulfur atom in the boat portion of the bicyclic ring compound. Wolff- Kishner reduction of the
ketone group gave 7-benzyl-3-thia-7-azabicyclo [3.3.1]
nonane, which was isolated as the hydroperchlorate . However, X-ray diffraction analysis of the
salt showed this solid to be a chair-chair conformer. Addition of phenylmagnesium
bromide to the
ketone gave a tertiary alcohol with the C-C6H5 bond being equatorial with respect to the thiane ring and axial with respect to the
piperidine ring. The reaction of the Grignard
reagent with the
ketone to give this alcohol seems to be very stereospecific. An X-ray analysis of the hydroperchlorate of the alcohol confirmed the system to be a chair-chair form in the solid. The title compounds were screened for antiarrhythmic activity in anesthetized mongrel dogs in which
myocardial infarctions had been created when the left anterior descending coronary artery was ligated. Vagal-induced slowing of the sinus mode firing rate was used to determine the underlying ventricular automaticity in the dogs, which averaged 164 +/- 27 beats/min. Ventricular pacing was initiated to rates between 240 and 390/min. This technique resulted in the induction of rapid and sustained
ventricular tachycardia. At doses of 3 and 6 mg/kg of
body weight, 7-benzyl-3-thia-7-azabicyclo [3.3.1]
nonane hydroperchlorate in alcohol (the
solution was administered intravenously) was able to suppress markedly the induced
ventricular tachycardia in five of six dogs. The compound also caused
a 10-15% increase in blood pressure within a few minutes. The antiarrhythmic properties of this compound and others of related structure are discussed, and some comparison is made with the action of
lidocaine in similar dog preparations.