Screening studies of new sukcinamine acid derivatives have been carried out, acute toxicity of these compounds and their effect on the functional state of the nervous system in laboratory animals has been studied. The purpose of the study: the examine the general effect and acute toxicity of 20 new compounds - derivatives of 3,5-dibromo-4-amino-benzene sulfonyl succinate amino acids, as well as the study of their effect on the functional state of the central nervous system. Research materials and methods. The investigated compounds are white with blue hue crystalline substances, odorless, with a clear melting point, soluble in polar organic solvents, solutions of caustic bases, mineral acids, alcohols. The structure of synthesized substances was confirmed by physic-chemical methods of elemental analysis, UV, IR, PMR and mass spectrometry, counter-synthesis, and purity of substances was controlled by thin-layer chromatography. The pharmacological activity of these substances was compared with the action of medicinal products: aminazine, caffeine-benzoate sodium, which met the requirements of the current specifications. Investigation of pharmacological activity of synthesized compounds was carried out by methods of special pharmacological screening. The study of neurotropic activity was performed on the interaction test with barbiturates. Experiments were carried out on non-breeding rats weighing 150-200 g for seven animals in each group. The investigational compounds were administered intraperitoneally at a dose of 0.01 LD50, and 30 minutes later, sodium ethamalum was injected 30 mg / kg intraperitoneally. The length of the medication sleep was judged by the time during which the animals were in the lateral position, that is, from the moment of loss of the reflex of the overturning. The results of the experiment were processed by the method of mathematical statistics using the Stjudent criterion. The analysis of the obtained results shows that LD50 of investigated gin-wines is in the range of 205 - 825 mg / kg and according to the classification of K.K. Sidorov data substances are low-toxic compounds. During the evaluation of the total action of the substances, the depressant effect of compounds 5, 9, 10 and 20 was observed. The most pronounced inhibitory effect on the nervous system was provided by Compound 19. In mice injected with compound 10, an increase in diuresis was observed, which is apparently associated with gain excretory renal function under the action of this substance. The introduction of the remaining compounds did not affect the amount of excreted urine. When studying the effects of derivatives of succinic acids on the functional state of the nervous system on the test of interaction with barbiturates, it was found out that all studied derivatives potentiate the duration of ethanol-sodium in white rats. Among the compounds studied, no substances were found that would cause animal stimulation and reduced the duration of drug sleep. It was also found out that substances 19 and 5 containing propylidene amine and amine radicals in their structure showed a marked such activity that exceeded such a comparator - aminazine. Derivatives of 3,5-dibromo-4-aminobenzene sulfonylsuccinamic acid affect the functional state of the central nervous system, increase the duration of drug sleep. Compound 19, the action of which exceeded the effect of the drug comparing the aminazine by 1.3 times, was the most active. The compounds 19 and 5, which exhibited pronounced neurotropic activity, are valuable for further study. The derivatives of succinic acids are a promising group of compounds for further pharmacological study to create drugs with sedative properties.
Keywords: succinic acid derivatives, acute toxicity, narcotic
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