Targeted synthesis of a series of 4-o-aryl- and 4-N-alkyl/arylquinazolines for stu-dying the JNK-kinase activity

I. Yu. Kapustyansky, S. M. Kovalenko, L. V. Yevsieieva, O. V. Zaremba

Abstract


To study the JNK-kinase activity of quinazoline derivatives a series of 4-O-aryl- and 4-N-alkylquinazolines have been synthesized in standard condition of nucleophilic substitution of 4-chloroquinazolines in the presence of potassium carbonate. 4-Chloroquinazolines have been obtained by the reaction of POCl3 with 3H-quinazolin-4-оnes using DMFA as a solvent. The abovementioned conditions have not yielded the desired results for the synthesis of 4-N-arylquinazolines, so acetic acid is used for the reaction catalysis. Therefore, 40 compounds of 4-(O)N-(aryl) alkylquinazolines class have been obtained. The structures of the compounds synthesized have been confirmed by NMR 1H-spectroscopy data. Characteristic signals of quinazoline protons in the second position are observed in the spectra of the compounds obtained. The signals of other protons are in good correlation with the expected structures. The melting points and purity of the compounds synthesized have been also determined. Using the PASS Professional programme the computer prediction of the biological activity of the compounds synthesized has been conducted; according to its results the compounds with the potential kinase activity have been selected. They are 4-N-arylquinazolines. The biological examination have been conducted under conditions in vitro in the culture medium of hepatocytes. The impact of substances on the activity of alanine aminotransferase has been determined and the activity of 4-N-(cyanoaryl)quinazolines as JNK-kinase inhibitors has been confirmed.

Keywords


4-O-aryl- and 4-N-alkyl(aryl)quinazolines; 4-N-(cyanoaryl)quinazolines; JNK-kinase inhibitors

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DOI: https://doi.org/10.24959/ophcj.14.792

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

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