DOI: https://doi.org/10.24959/nphj.14.1962

Synthesis and properties of n-[2-(benzoylamino) (2-oxoindolin-3-ylidene)acetyl]amino acids ethyl esters

O. O. Altukhov

Abstract


Analysis of scientific and patent literature testifies that search of biologically active compounds among derivatives of 2-oxoindoline is prospective. They include well-known amino acids (tryptophane), neurohormone serotonine, a number of natural alkaloids and synthetic drugs (indomethacin, dimecarbin). For many years at the Analytical chemistry department of the National University of Pharmacy the extensive studies have been conducted in the field of development of synthetic methods and the study of physicochemical and biological characteristics of hetarylcarboxylic acids, in particular, 2-oxaindolineacetic acids and products of their transformation in order to search active and harmless medicines. The pharmacological research of (2-oxoindolin-3-ylidene)-2-oxoacetic acid derivatives allow making a conclusion that the highest nootropic activity is shown by substances containing amino acid esters moieties. Extending directions of the target-based search for biologically active compounds and basing on the previous studies it has been decided to include the fragments of amino acids into the core structure – 2-(benzoylamino)(2-oxoindolin-3-ylidene)-2-oxoacetic acid and to carry out the synthesis of N-[2-(benzoylamino)(1-R-2-oxoindolin-3-ylidene)acetyl]amino acids ethyl esters. The structure of the compounds synthesized has been confirmed by the data of elemental analysis, IR- and 1H NMRspectroscopy. In 1H NMR spectrum of N-[2-(benzoylamino)(1-R-2-oxoindolin-3-ylidene)acetyl]glycine the signal of the methylene group of the amino acid residue is observed as a duplet at δ 4.0 ppm. The signal of the carboxyl group proton in the spectrum of the acid is not observed as a result of deuterium exchange. The signal of СН2-group is shifted downfield (4.08 ppm) for the ester. The signals of the ethoxy group are recognized as a quartet at 4.20 ppm (2H, CH2) and a triplet at 1.21 ppm (3H, CH3).


Keywords


synthesis; derivatives of 2-(benzoylamino)(1-R-2-oxo-1,2-dihydro-3H-indol-3-ylidene) acetic acids; azlactone; amino acids; ethyl esters

Full Text:

PDF

References


Беллами Л. Инфракрасные спектры сложных молекул. – М.: Изд-во иностранной литературы, 1963. – 590 с.

Державна фармакопея України / Державне підприємство «Науково-експертний фармакопейний центр». – 1-е вид. – Х.: ООО «РИРЕГ», 2001. – 556 с.

Колісник С.В., Болотов В.В., Алтухов О.О., Шишкіна С.В. // ЖОФХ. – 2010. – Т. 8, вип. 3 (31). – С. 65-70.

Наканиси К. Инфракрасные спектры и строение органических соединений. – М.: Мир, 1965. – 216 с.

Пат. на корисну модель №38064 (2008) Україна // Б.В. – 2008. – №24.

Пат. на винахід №89542 (2010) Україна // Б.В. – 2010. – №3.

Пат. на винахід №90357 (2010) Україна // Б.В. – 2010. – №8.

Шатілов О.В., Штриголь С.Ю., Колісник С.В. та ін. // Актуальні проблеми сучасної медицини: Вісник Української медичної стоматологічної академії. – 2009. – Т. 9, Вип. 2(26). – С. 139-142.

Штриголь С.Ю., Стіхарний О.О., Колісник С.В. та ін. // Вісник фармації. – 2008. – №4 (56). – С. 75-77.

Штриголь С.Ю., Стіхарний О.О., Колісник С.В. та ін. // Вісник фармації. – 2008. – №3 (55). – С. 60-63.

Andreani A., Rambaldi M., Locatelli A. et al. // Acta Pharm. Nord. – 1991. – Vol. 3, №1. – P. 5-8.

Bouchikhi F., Rossignil E., Sancelme M. et al. // Eur. J. Med. Chem. – 2008. – №43. – P. 2316-2322.

Breitmaier E. Structure elucidation by NMR in organic chemistry. – 3rd ed. – Chichester: John Wiley & Sons, 2002. – 258 p.

Gruda J. // Can. J. Chem. – 1972. – Vol. 50, №1. – P. 18-23.

Hodjes R., Shannon J.S., Jamieson W.D., Taylor A. // Can. J. Chem. – 1968. – Vol. 46, №13. – P. 2189-2194.

Kenichi O., Ryota Sh., Takashi O. et al. // Bioorg. & Med. Chem. – 2008. – Vol. 16, №23. – P. 10001-10012.

Nagarajan K., Talwaker P., Goud A. et al. // Ind. J. Chem. «В». – 1998. – Vol. 27, №12. – Р. 1113-1123.

Stefanovich G., Mihailovich S. // Glasnik Khem. Drushiva. – 1959. – №22. – P. 459-471.

Terzioglu N., Karali N., Gürsoy A. et al. // ARKIVOC. – 2006. – Vol. 1. – P. 109-115.

Wikerson W., Kergaye A., Tam W. // J. Med. Chem. – 1993. – Vol. 36, №20. – Р. 2899-2907.


GOST Style Citations






Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abbreviated key title: Vìsn. farm.

ISSN 2415-8844 (Online), ISSN 1562-7241 (Print)