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


  • S. G. Isaev National University of Pharmacy, Ukraine
  • H. O. Yeryomina National University of Pharmacy, Ukraine
  • T. V. Zhukova National University of Pharmacy, Ukraine
  • T. M. Kryuchkova National University of Pharmacy, Ukraine
  • G. P. Zhegunova National University of Pharmacy, Ukraine



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


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.


Берхин Е.Б. // Хим.-фармац. журн. – 1977. – Т. 11, №5. – С. 3-11.

Девяткина А.А., Исаев С.Г., Бризицкий А.А., Яременко В.Д. // Матер. 5-й Междунар. науч. конф. «Фарм. образование 2013». – Воронеж, 2013. – С. 279-284.

Девяткіна А.О., Ісаєв С.Г., Жегунова Г.П., Яременко В.Д. // Укр. журн. клін. лаб. мед. – 2013. – Т. 8, №1. – С. 238-243.

Доклінічні дослідження лікарських засобів: метод. рекоменд. / За ред. О.В.Стефанова. – К.: Авіценна, 2001. – 528 с.

Ісаєв С.Г. Синтез, реакційна здатність і біологічна активність похідних орто-галогенoбензойних, ароматичних амінокислот та акридину: дис. … д-ра фармац. наук: 15.00.02. – Х., 2008. – 357 с.

Машковский В.Д. Лекарственные средства. – 16-е изд., испр. и доп. – М.: Новая волна, 2012. – 1216 с.

Пат. 91422 Україна, МПК С 07 С 229/58, А 61 К 31/196, А 61 Р 29/00, А 61 Р 31/10. 3-Нітро-N-(3’-ніт-рофеніл)антранілова кислота, що проявляє протизапальну, аналгетичну, діуретичну та протигрибкову активність / С.Г.Ісаєв, І.А.Зупанець, О.А.Бризицький та ін. – Заявка №200813252. – Заявл.: 17.11.2008. Опубл.: 26.10.2010. – Бюл. №14.

Alferova D.O., Gritsenko I.S., Isaev S.G. // Харбашиси (Kazakhstan). – 2013. – №1 (62). – Р. 214-219.

Anzali S., Barnickel G., Cezanne B. et al. // J. Med. Chem. – 2001. – №4 (15). – Р. 2432-2437.

Chikina E.L., Isaev S.G., Svechnikova E.N. / Proceedings of the IVTN – 2004 Computer application in scientific researches IVTN – 2004. – P. 31.

Isaev S.G., Svechnikova O.M., Devyatkina A.O., Zhukova T.V. // News of Pharmacy. – 2013. – №4 (76). – P. 15-18.

Isaev S.G., Svechnikova O.M., Devyatkina A.O. et al. // News of Pharmacy. – 2013. – №2 (74). – P. 45-48.

Gwanyanya A., Macianskiene R., Bito V. et al. // Biochem. and Biophys. Res. Communications. – 2010. – Vol. 402, issue 3. – P. 531-536.

Simons L., Caprathe B., Callahan M. et al. // Bioorg. Med. Chemistry Lett. – 2009. – Vol. 19, issue 3. – P. 654-657.






Synthesis and Analysis of Biologically Active Substances