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

Authors

  • K. Yu. Netyosova National University of Pharmacy, Ukraine
  • S. S. Kovalenko National University of Pharmacy, Ukraine
  • O. H. Drushlyak National University of Pharmacy, Ukraine
  • I. O. Zhuravel National University of Pharmacy, Ukraine
  • S. M. Kovalenko V. N. Karazin Kharkiv National University, Ukraine
  • E. L. Toryanik National University of Pharmacy, Ukraine

DOI:

https://doi.org/10.24959/nphj.16.2095

Keywords:

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

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.

Author Biographies

K. Yu. Netyosova, National University of Pharmacy

Assistant of Department of Toxicological Chemistry

S. S. Kovalenko, National University of Pharmacy

Quality Management Department

O. H. Drushlyak, National University of Pharmacy

Quality Management Department

I. O. Zhuravel, National University of Pharmacy

Department of Toxicological Chemistry

S. M. Kovalenko, V. N. Karazin Kharkiv National University

Department of Organic Chemistry

E. L. Toryanik, National University of Pharmacy

Department of Clinical Laboratory Diagnostics

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.

Downloads

Published

2016-06-13

Issue

Section

Synthesis and Analysis of Biologically Active Substances