Structure-activity relationship in cinnamamides. 2. Synthesis and pharmacological evaluation of some (E)- and (Z)-N-alkyl-alpha, beta-dimethylcinnamamides substituted on the phenyl group.
Several (E)- and (Z)-N-alkyl-alpha,beta-dimethylcinnamamides variously substituted on the phenyl group were synthesized from their corresponding acids and characterized through their NMR spectra. The compounds were tested to determine the relationship existing between their action on the CNS and the activity exhibited by the corresponding amides unsubstituted on the phenyl, previously studied. Substitution with the same group always had the same effects on the biological activity of the (E)-N-alkyl-alpha,beta-dimethylcinnamamides selected; these effects mainly regarded anticonvulsant activity which is the most noteworthy action of these compounds. This activity was reduced by electron-donating substituents and increased by electron-withdrawing ones. In the Z series the p-phenyl substitution with a halogen reduced or suppressed the CNS stimulant activity exhibited by the parent compounds.
D000478:Alkylation; D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis; D001522:Behavior, Animal / Q000187:drug effects; D002934:Cinnamates / Q000138:chemical synthesis* / Q000494:pharmacology; D004341:Drug Evaluation; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D051379:Mice; D013329:Structure-Activity Relationship; D014202:Tremor / Q000517:prevention & control
D000577:Amides; D000927:Anticonvulsants; D002934:Cinnamates