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

Abstract

3-{[(1-Methyl-1 H -tetrazol-5-yl)imino]methyl}quinoline-2-thiol and 3-{[(2-methyl-2 H -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 H -tetrazol-5-yl)amino]-2-phenyl-4 H -thiopyrano[2,3- b ]quinoline-3-carbaldehyde, 4-[(2-methyl-2 H -tetrazol-5-yl)amino]-2-phenyl-4 H -thiopyrano[2,3- b ]-quinoline-3-carbaldehyde, and 4-hydroxy-2-phenyl-4 H -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-4 H -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-1 H -tetrazol-5-yl)imino]-methyl}quinoline-2-thiol has a higher activity than 3-{[(2-methyl-2 H -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.

Update on thiopyran-fused heterocycle synthesis (2013–2024)

“…48 Very recently, the synthesis of thiopyrano[2,3-b]quinolines incorporating a tetrazole moiety was reported by Khramchikhin et al, and the antiviral activity of synthesized compounds was studied. 49 The reaction took place by an Scheme 17 Sc(OTf ) 3 -catalyzed diastereoselective synthesis of indole-annulated thiopyrans.…”

“…Very recently, the synthesis of thiopyrano[2,3- b ]quinolines incorporating a tetrazole moiety was reported by Khramchikhin et al , and the antiviral activity of synthesized compounds was studied. 49 The reaction took place by an initial condensation of carbaldehyde 102 with 1-methyl-1 H -tetrazole-5-amine 159 to yield imine 160 . The latter underwent thiol-Michael and aza-Morita-Baylis-Hilman reactions with aldehyde 161 , yielding final annulated product 162 .…”

Novel 1,2,4-Triazole- and Tetrazole-Containing 4H-Thiopyrano[2,3-b]quinolines: Synthesis Based on the Thio-Michael/aza-Morita–Baylis–Hillman Tandem Reaction and Investigation of Antiviral Activity

“…The reaction between 2-mercaptoquinoline-3-carbaldehyde and the key annulation reagent, 3-phenyl-2-propynal, was used as our model system. We demonstrated, for the first time, that the interaction of these reagents proceeds through a tandem reaction pathway involving the thio-Michael/Morita-Baylis-Hillman reaction, resulting in the formation of 4-hydroxy-2-phenyl-4H-thiopyrano[2,3-b]quinoline-3-carbaldehyde 1 (Scheme 1) [22]. Usually, in both intermolecular and intramolecular Morita-Baylis-Hillman reactions, relatively expensive tertiary amines such as DABCO, DBU, and tertiary phosphines are used as catalysts and these reactions can endure for extended durations, spanning hours or even weeks [20].…”

“…Synthesis and analytical data for compounds 1, 5a, 6a, 9a, and 10a were described by us in the short communication [22]. Crystals of compounds 1, 9a and 10a were obtained from DMF for RSA.…”