DOI: https://doi.org/10.24959/nphj.14.1963

Synthesis, structure and research of the pharmacological activity of methyl esters of 6-nitro-n-phenilanthranilic acids

S. G. Isaev, H. O. Yeryomina, T. V. Zhukova, T. M. Kryuchkova, G. P. Zhegunova

Abstract


Analysis of scientific and patent literature shows the promising results of searching biologically active compounds among derivatives of aromatic aminoacids. For many years at the Medical Chemistry department of the National University of Pharmacy the research has been conducted in the field of development of synthetic methods and study of physico-chemical and pharmacological properties of aromatic acids, in particular, N-phenylanthranilic acids and products of their transformation in order to search active and harmless medicines. The synthesis of methyl esters of 6-nitro-N-phenylanthranilic acids has been carried out by Fisher esterification in the absolute methanol medium in the presence of concentrated sulfuric acid. Substituted 6-nitro-N-phenylanthranilic acids have been obtained by Ullmann reaction by the interaction of 6-nitro-2-chlorobenzoic acids with arylamines and by arylation of 6-nitro-N-phenylanthranilic acids by halogenobenzenes derivatives in the medium of n-amylalcohol, in the medium of dimethylformamide, without a solvent in the presence of copper or CuO. The structure of the compounds has been confirmed by elemental analysis, IR- and NMR-spectroscopy. The purity has been controlled by the method of thin-layer chromatography in methanol-hexane (1:1.5) and ethylacetate-methanol-ammonia (8.5:1:0.5). The computer prognosis of possible types of the biological activity of 9 methyl esters of 6-nitro-N-phenylanthranilic acids synthesized for the first time has been conducted with the help of PASS programme. It has been found experimentally that the substances synthesized possess the anti-inflammatory, analgesic, diuretic, bacteriostatic, fungistatic and antidiuretic activities. According to the classification by K.K.Sydorov the compounds synthesized when introduced intragastrically belong to low toxic compounds (DL50=1200-2500 mg/kg). Some regularities of the “structure – biological activity – toxicity” relationship have been determined.


Keywords


synthesis; methyl esters of N-phenylanthranilic acids; pharmacological activity

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