Relations between chemical structure, physico-chemical properties, chemical reactivity and effect of various positionally isomeric local anesthetics 31.2.

Abstract:  1. In the introduction, a short survey on the effect of different structural isomers on the activity of drugs is giben. The inductive, resonance and steric effect of the ring substitution are discussed and probable mechanism of local-anesthetic action is dealth with. 2. As model substances in this work, the diethylamino-ethyl-e ster-hydrochlorides of amino-, butylamino, butoxy- and butyl-benzoic acids are synthesized and their purity tests as well as the spectroscopic identifications are made. Further more the data on the pKa, ionisation degree, turbidity pH, water solubility of the bases, partition coefficient and the surface activity of these substances are given. 3. The electron density of the carbonyl groups (sigma-values and IR-frequencies), the hydrolysis constants and the protein-binding values are studied as the measure of the chemical reactivity of the model substances. 4. Although a fairly good correlation between different physico-chemical properties of these substances was found, a satisfactory correlation of the hydrolysis constants, the partition constants, the electronic densities as well as the sigma-constants to the local anesthetic activity of these substances is compared only in the p-substituted compounds. For the inconsistency in the o- and m-derivatives, the steric effect of the substituents could be called responsible.