Synthesis of ω-(7-aryl-8-oxo-7,8-dihydro[1,2,4]-triazolo-[4,3-a]pyrazin-3-yl)alkylcarboxylic acids and their amides as perspective pharmaceutical agents

K. Yu. Netyosova, S. S. Kovalenko, O. H. Drushlyak, I. O. Zhuravel, S. M. Kovalenko, E. L. Toryanik

Abstract


Previously designated a comfortable and effective scheme of 3,7-disubstituted [1,2,4]triazolo[4,3-a]pyrazin-8(7H)-ones synthesis was spread to derivatives of ω-(7-aryl-8-oxo-7,8-dihydro[1,2,4]triazolo[4,3-a]pyrazin-3-yl) alkylcarboxylic acids. Our approach consists of application of reaction of formerly described 3-hydrazinopyrazin-2-ones with cyclic anhydrides of dicarbonic acids such as succinic and glutaric anhydrides. Consequent cyclization was carried out in DMFA by means of boiling during 12 hours and resulted in creation of 3-(7-aryl-8-oxo-7,8-dihydro[1,2,4]triazolo[4,3-a]pyrazin-3-yl)propanoic acids or 4-(7-aryl-8-oxo-7,8-dihydro[1,2,4]triazolo[4,3-a]pyrazin-3-yl) butanoic acids with yield 51 – 65%. To obtain amides we used activation of carboxylic group of obtained acids by means of application of carbonilmidiimidazolamide along with anhydrous dioxane with intermidiate creation of imidazolilamide, subsequent reaction with both of aliphatic and aromatic amines was carried out by means of boiling for 12 hours. Yield of obtained amides was approxiametely 50 – 92%. The structure of obtained compounds was proved by means of elemental analysis and 1H NMR spectroscopy data. The synthesized compounds are of certain interest as potential pharmacologic agents associated with the regulation of lipid metabolism and ability of these compounds to have an impact on the level of lipoproteins, purine metabolism and receptivity of tissues to glucose.

Keywords


3-hydrazinopyrazin-2(1H)-one; [1;2;4]triazolo[4;3-a]pyrazin-8(7H)-one; succinic anhydride; glutaric anhydride; cyclization; amide formation

Full Text:

PDF

References


Doukhan G., Huynh Dinh Tam, Bisagni E. et al. // J. Med. Chem. – 1979. – Vol. 14, №4. – P. 375–380.

Kovalenko S.S., Kulikovska K.Yu., Drushlyak O.G. et al. // Chem. of Het. Compounds. – 2014. – №8. – Р. 1243–1249.

Koyama G., Umezawa H. // J. of Antibiotics. – 1965. – № 18A. – Р. 175–177.

Kulikovska K.Yu., Kovalenko S.S., Drushlyak O.G. et al. // ЖОрФХ. – 2014. – Vol. 12, №2 (46). – Р. 32–35.

Kulikovska K.Yu., Kovalenko S.S., Drushlyak O.G. et al. // Фармация Казахстана. – 2014. – № 9. – Р. 55–57.

Orechovich V.N. Institute of Biomedical Chemistry. PASS: http://www.pharmaexpert.ru/PASSOnline/.

Pat. US 2013/0196986 A1. Triazolopyrazinones as P2X7 receptor antagonists / M. Labroli, M. F. Czarniecki, C. S. Poker; applicant Merck Sharp & Dohme. – № EP2619204 A4; st. 16.09.2011; app. 20.03.2013.

Sarfati R. S., Gouyette C., Igolen J. et al. // J. Org. Chem. – 1979. – №44 (7). – Р. 1028–1035.

Sarges R., Howard H.R., Browne R.G. et al. // J. of Med. Chem. – 1990. – Vol. 33, № 8. – P. 2240–2254.

Zhou J., Yang M., Schneller S. W. // Tetrahedron. – 2004. – № 45. – Р. 8233–8234.


GOST Style Citations






DOI: https://doi.org/10.24959/88775

Abbreviated key title: Vìsn. farm.

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