[Preparation and anticonvulsant activity of new potential beta-adrenoreceptor blockers]. / Príprava a antikonvulzívna aktivita nových potenciálnych blokátorov beta-adrenoreceptorov.

Within the framework of a structure-effect relationships study in a group of new beta-adrenoreceptor blockers, a series of new derivatives derived from p-hydroxyacetophenone with modifications in the basic moiety of the side chain was prepared. The initial p-hydroxyacetophenone prepared by Fries rearrangement of phenylacetate in a reaction with 2-(chloromethyl)oxirane yields 1-[4-(2-oxiranylmetoxy)phenyl]-1-etanone, which combines with the appropriate amines to produce final substances. They were isolated either in the form of free bases, or salts with fumaric acid. Their structure was confirmed by interpretations of the IR, 1H-NMR and 13C-NMR-spectra. Within the framework of pharmacological evaluation of the prepared agents, the anticonvulsive effect as a protective effect against pentetrazole spasms was examined. The results of the evaluation were compared with the values of their distribution coefficients.

[Changes in basic nitrogen in a group of potential new beta- adrenolytics--derivatives of p-hydroxyacetophenone and p-hydroxypropiofenone]. / Obmeny na bázickom dusíku v skupine nových potenciálnych betaadrenolytík--derivátov p-hydroxyacetofenónu a p-hydroxypropiofenónu.

Within the relationship of the structure and effect of new beta-adrenolytic agents derivatived from p-hydroxyacetophenone and p-hydroxypropiophenone with a propoxymethyl group in the lipophilic part of the molecule and with a propanamine, a butanamine and a pyrrolidine in the side-chain were studied. In order to prepare these substances, a procedure was selected from several tested ones, in which 4-hydroxy-3propoxymethylphenylketone were treated with chloromethyloxirane and subsequent reaction a hydrobromic acid were prepared 4-(3-brom-2-hydroxypropoxy)-3-propoxymethylalkylketone. Final substances were prepared reaction with amine. The structure of prepared compounds was confirmed on the basic interpretation of the IR, UV and 1H NMR spectra. The results of pharmacological evaluation of selected compounds showed a significant beta 1-blocking activity lower than acebutolol. Their local anesthetic activity is low according with their partition coefficients. The characteristic of the prepared compounds was supplemented by the determination of their partition coefficients, surface tension, dissociation constants and acute toxicity.

[Derivatives of para-hydroxyacetophenone and para-hydroxypropiophenone as a potential new beta-adrenolytic agent]. / Deriváty para-hydroxyacetofenónu a para-hydroxypropiofenónu ako nové potenciálne beta-adrenolytiká.

Within the framework of the study of the structure-effect relationship, a series of novel potential beta-adrenolytic agents derived from p-hydroxyacetophenone and p-hydroxypropiophenone with an alyloxymethyl and a cycloalkyloxymethyl group in the lipophilic part of the molecule and an isopropyl and a tert-butyl group in the hydrophilic part on the basic nitrogen were prepared by means of a well-tried method. The structure of the prepared drugs was confirmed on the basis of interpretation of the IR, UV, 1H-NMR and mass spectra. The results of pharmacological evaluation of selected drugs show that the agents poses beta-adrenolytic and antiarrhythmic activity. From the viewpoint of comparison of the individual drugs subjected to testing the presence of an alyl seems more advantageous than that of a cyclohexyl. The characteristic of the prepared drugs was supplemented by the determination of their partition coefficients, surface tension and acute toxicity.

Relationship between the structure of carbonylcyanide phenylhydrazones and inhibition of growth of microorganisms, stimulation of respiration of yeast cells and rat liver mitochondria.

The effect of ten derivatives of carbonylcyanide phenylhydrazone on growth of bacteria, yeast and different species of filamentous fungi was investigated. In yeast and mitochondria isolated from rat liver the effect of these derivatives on the respiratory activity was also followed. The relative efficiency of the individual derivatives of carbonylcyanide phenylhydrazone was determined on the basis of the results obtained. It was shown that derivatives, in which the substituent on the benzene ring causes simultaneously an increase of acidity and lipophilicity of the derivative as compared with the non-substituted carbonylcyanide phenylhydrazone (4-trifluoromethoxy-, 3-chloro-, 4-chloro and 3,4-dichloro-derivatives) were most effective.