Synthesis of isomeric 4-(-methyltetrazolylamino)-2-phenyl-4-thiopyrano[2,3-]quinoline-3-carbaldehydes and 4-hydroxy-2-phenyl-4-thiopyrano[2,3-]quinoline-3-carbaldehyde based on tandem thiol-Michael and (aza)-Morita-Baylis-Hillman reactions and an study of the activity of the obtained compounds against influenza virus.

Unlabelled: 3-{[(1-Methyl-1-tetrazol-5-yl)imino]methyl}quinoline-2-thiol and 3-{[(2-methyl-2-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-1-tetrazol-5-yl)amino]-2-phenyl-4-thiopyrano[2,3-]quinoline-3-carbaldehyde, 4-[(2-methyl-2-tetrazol-5-yl)amino]-2-phenyl-4-thiopyrano[2,3-]-quinoline-3-carbaldehyde, and 4-hydroxy-2-phenyl-4-thiopyrano[2,3-]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-4-thiopyrano[2,3-]quinoline-3-carbaldehyde with a 1-methyl- or 5-amino-2-methyltetrazolyl fragment decreased antiviral activity. At the same time, 3-{[(1-methyl-1-tetrazol-5-yl)imino]-methyl}quinoline-2-thiol has a higher activity than 3-{[(2-methyl-2-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.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10593-022-03083-w.