Enhancement of the base for 3,7-disubstituted [1,2,4]triazolo[4,3-a]pyrazin-8(7H)-one derivatives as promising pharmaceutical agents

K. Yu. Kulikovska, S. S. Kovalenko, O. G. Drushlyak, I. O. Zhuravel, S. M. Kovalenko

Abstract


A suitable and effective scheme for the synthesis of 3,7-disubstituted [1,2,4]triazolo[4,3-a]pyrazin-8(7H)-ones has been suggested and tested. It can provide a wide chemical diversity of the final products containing practically any substituent in position 3. The scheme previously developed starts from esters of oxalamic acid following with the cyclization of intermediate 3-hydrazinopyrazin-2-ones with carbonyl-containing compounds (ortho-esters or alkylcarbonic acid anhydrides). To introduce aryl or heteryl substituents in position 3 of the heterocyclic system we propose to use the reaction of 3-hydrazinopyrazin-2-ones with the corresponding carbonic acids preliminary activated by carbonyldiimidazole (CDI). The further cyclization is carried out by reflux for 24 hours in anhydrous DMFA. The structure of the compounds obtained has been proven by elemental analysis and 1H NMR spectroscopy data. Formation of [1,2,4]triazolo[4,3-a]pyrazin-8(7H)-one condensed system is in good correlation with spectral data, and is confirmed by the presence of signals of H-5 and H-6 protons of the pyrazinone fragment as doublets at d 7.15-7.28 ppm and d 7.50-7.59 ppm, respectively. The compounds synthesized are of particular interest as potential pharmacological objects with the cytotoxic, membrane-stabilizing, cerebroprotective, cardioprotective activity.

Keywords


3-hydrazinopyrazin-2(1H)-one; [1,2,4]triazolo[4,3-a]pyrazin-8(7H)-one; cyclization

Full Text:

PDF

References


Reinhard Sarges, Harry R. Howard, Roland G. Browne, Lorraine A. Lebel, Patricia A. Seymour, B. Kenneth Koe. J. of Medicinal Chemistry, 1990, Vol. 33, No.8, pp.2240-2254.

Mignani S., Stutzmann J.-M., Vuilhorgne M. Trends in Heterocyclic Chemistry, 2002, Vol. 8, pp.49-60.

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

Kovalenko S.S., Kulikovska K.Yu., Drushlyak O.G., Zhuravel I.O., Kovalenko S.M., Chernykh V.P. Chem. of Heterocyclic Compounds, 2014, Impress.

Schneller S.W., May J.L. J. Heterocyclic Chem, 1978, Vol. 15, pp.987-992.


GOST Style Citations






DOI: https://doi.org/10.24959/ophcj.14.794

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

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)