Structure—Activity Relationship of Local Anesthetics Based on Alkynylpiperidine Derivatives

The influence of the nature of the acyl (propionyl and benzoyl) moiety and the piperidine ring C 4 substituent on the activity of several alkynylpiperidine derivatives was studied. The presence of an alkyl (hexyl) radical on the triple bond of the piperidine ring C 4 substituent in the infiltration anesthesia model had a positive effect on the anesthesia index and the duration of both total and general anesthesia as compared to lidocaine, novocaine, and trimecaine taken as reference drugs. The ester of 4-(octyn-1-yl)piperidol-1-propionic acid was the most active anesthetic among the studied compounds. Modification of the triple bond (exhaustive hydrogenation and hydration) led to a decrease in the duration of anesthesia. The activity of the benzoate was greater than that of the propionate in the propionate-benzoate pair.