SYNTHESIS OF ISOMERIC 4-(<i>N</i>-METHYLTETRAZOLYLAMINO)-2-PHENYL-4<i>H</i>-THIOPYRANO[2,3-<i>b</i>]QUINOLINE-3-CARBALDEHYDES AND 4-HYDROXY-2-PHENYL-4<i>H</i>-THIOPYRANO[2,3-<i>b</i>]QUINOLINE-3-CARBALDEHYDE BASED ON TANDEM THIOL-MICHAEL AND (AZA)-MORITA–BAYLIS–HILLMAN REACTIONS AND AN <i>in vitro</i> STUDY OF THE ACTIVITY OF THE OBTAINED COMPOUNDS AGAINST INFLUENZA VIRUS

Abstract

3-{[(1-Methyl-1H-tetrazol-5-yl)imino]methyl}quinoline-2-thiol and 3-{[(2-methyl-2H-tetrazol-5-yl)imino]methyl}quinoline-2-thiol were synthesized. The sequence of the thiol-Michael reaction and the (aza)-Morita–Baylis–Hillman reaction yielded 4-[(1-methyl-1H-tetrazol-5-yl)amino]-2-phenyl-4H-thiopyrano[2,3-b]quinoline-3-carbaldehyde, 4-[(2-methyl-2H-tetrazol-5-yl)amino]-2-phenyl-4H-thiopyrano[2,3-b]quinoline-3-carbaldehyde, and 4-hydroxy-2-phenyl-4H-thiopyrano[2,3-b]quinoline-3-carbaldehyde.  Cytotoxicity and antiviral activity against the A/Puerto Rico/8/34 (H1N1) influenza virus strain in MDCK cell culture were determined for the obtained compounds. The study showed that the replacement of the hydroxyl group in 4-hydroxy-2-phenyl-4H-thiopyrano[2,3-b]quinoline-3-carbaldehyde with a 1-methyl- or 5-amino-2-methyltetrazolyl fragment decreased antiviral activity. At the same time, 3-{[(1-methyl-1H-tetrazol-5-yl)imino]-methyl}quinoline-2-thiol has a higher activity than 3-{[(2-methyl-2H-tetrazol-5-yl)imino]methyl}quinoline-2-thiol. This fact indicates a possible relationship between the arrangement of substituents in the tetrazole ring and the antiviral activity of the tested heterocyclic system.