Relationships between the lipophilicity of some 1,4-piperazine derivatives of aryloxyaminopropanols and their beta-andrenolytic activity.

Nineteen 1,4-piperazine derivatives of aryloxyaminopropanol were evaluated with respect to beta-adrenolytic activity. The retention factors obtained from HPLC, RM values obtained from partition TLC and the lipophilic Hansch's (4) constants pi were determined and the compounds were studied with respect to their lipophilicity based on chromatographic properties. The study of the influence of different substituents introduced at the para position on the phenyl ring on the retention factor indicated the log k vs. the number of carbon atoms in R1 substituent to be a linear relationship. Attempts have been made to relate the beta-adrenolytic activity to the lipohydrophilic parameters by deriving a quantitative relationship between them. Significant parabolic correlation was observed between the beta-adrenolytic activity and the logarithm of the retention factor, log k. An analogous relationship was obtained between the beta-adrenolytic activity of the compounds and the RM values obtained from partition TLC as well as Hansch's lipophilic constants pi.

[The effect of piperazine analogs of aryloxyaminopropanol (IIIq and IIIb) on the occurrence of reperfusion dysrhythmias in an in vivo experiment on rats]. / Vplyv piperazínových analógov aryloxyaminopropanolu (IIIq a IIIb) na výskyt reperfúznych dysrytmií u potkanov v pokusoch in vivo.

The present experimental study reports the beneficial effects of newly synthetized substances IIIq and IIIb in vivo. These aryloxyaminopropanol drugs have been shown to antagonize the contraction caused by calcium comparable to verapamil and flunarizine in the model of the isolated guinea pig terminal ileum. Effects of substances on both the incidence of arrhythmias during ischemia and the reperfusion period and mortality were investigated in the rat model ischemia-reperfusion injury. We can conclude that compound IIIq in a dose of 10(-6) mol/kg is effective in reducing the incidence of reperfusion-induced arrhythmias. Substance IIIb (10(-6) mol/kg) administered before ischemia was not able to suppress arrhythmias in the rat model of myocardial infarction and reperfusion.

[Piperazine analogs of aryloxyaminopropanols and a study of their effects on a model of the isolated guinea pig ileum]. / Piperazinové analogy aryloxyaminopropanolu a studium jejich úcinku na modelu izolovaného morcecího ilea.

Seven compounds belonging to the group of aryloxyaminopropanols with carbamate substitution of the aromatic ring and with derivatives of N-phenylpiperazine in the lipophilic part were prepared by a well-tried method. Selected drugs were pharmacologically evaluated by in vitro experiments. Aryloxyaminopropanol drugs confirmed their anti-calcium activity on the intestinal model. Significant anti-calcium activity of agents IIIq and IIIb (pA2 = 6,83 +/- 1,47; 7, 12 +/- 1, 12 was comparable to that found for the standards verapamil and flunarizine. These compounds were selected for in vivo experiments and evaluated for their effect on reperfusion-induced arrhythmias in anaesthetized rats. Results of these evaluations are given in the next article.

[Preparation and pharmacologic characteristics of aryloxyaminopropanol derivatives with an assumed cardiovascular effect]. / Príprava a farmakologická charakteristika aryloxyaminopropanolových derivátov s predpokladaným kardiovaskulárnym pôsobením.

In an attempt to prepare drugs favourably influencing pathologically changed functions of the cardiovascular system, such as hypertension and ischemic cardiac disease, several chemical compounds were prepared in which benzhydrylpiperazine, alkyl, or substituted phenylpiperazine (fragments of the structures of calcium antagonists) were bound to the fundamental aryloxyamino-propanol skeleton (the carrier of beta-adrenolytic effect). The selected four compounds underwent basic pharmacological analysis. In experiments on the isolated spontaneously beating guinea-pig atria (beta 1), three compounds competitively inhibited the positively chronotropic effect of isoprenaline (pA2 = 6.40-7.24) and in experiments on the isolated tracheal guinea-pig muscle they antagonised the relaxation effect of isoprenaline beta 2, the pA2 values ranging from 5.90-7.58. It follows from the experiments on the isolated guinea-pig aorta contracted with 50 mM KCl that all compounds under study possess mild relaxation effects, the intensity of which is, however, lower than in the used standards flunarizine and verapamil.