[Investigation of some basic propyl(alkyl)-phenyl ketones with local-anesthetic activity (author's transl)].
We synthetised several ketone analogues of procain (II) with different lipophilic substituents (XVI). In order to investigate structure-activity relationship, the Rm values (measure for the partition coefficient), the -CO- wave frequency (expression of electron density) and the local anesthetic activity (rabbit cornea) were determined. The studied lipophilic substituents do not influence the inductive or mesomeric effect on the carbonyl oxygen and so do not increase its electron density. On the other hand, they do increase the partition coefficient, therefore the hydrophobic binding effect of the substituents is improved. The lower efficacy of the carbonyl group in ketones against the acrboxyl group can be compenstaed for by introduction of groups with higher liposolubility, so that even in ketones it is possible to prepare substances with high local-anesthetic activity.
D000779:Anesthetics, Local / Q000138:chemical synthesis*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology; D008055:Lipids; D011343:Procaine / Q000031:analogs & derivatives / Q000138:chemical synthesis; D011817:Rabbits; D012995:Solubility; D013329:Structure-Activity Relationship
D000779:Anesthetics, Local; D007659:Ketones; D008055:Lipids; D011343:Procaine
Untersuchung einiger basischer Propyl(Aklyl)-phenyl-ketone mit lokalanästhetischer Wirkung