Synthesis and Some Properties of New 5-Hydroxy-2-[(hetarylthio)methyl]-4H-pyran-4-ones

V. V. Dotsenko,D. D. Guz,V. K. Kindop,E. E. Netreba,I. V. Aksenova,N. A. Aksenov,D. T. Tebiev

doi:10.1134/s107036322109005x

Abstract

The reaction of 2-thioxoazines with chlorokojic acid in the presence of KOH in DMF led to the formation of new hybrid molecules containing fragments of kojic acid and azaheterocycle linked by the SCH2 spacer. In silico prediction of bioavailability parameters was carried out, possible protein targets were predicted by the protein ligand docking method.

Highlights

One of the most accessible methods of functionalization of kojic acid is its transformation into bromo- or chlorokojic acid 11, with further replacement of the halogen atom by various nucleophiles such as thioureas [28,29,30,31,32,33], alkyl mercaptans [29, 30, 34], thiophenols [21, 35], sodium arylsulfinates [36], alkali metal thiocyanates [36,37,38,39], S-glycosylisothiuronium salts [40], various mercaptoazoles [22, 25, 28, 29, 41], 2-mercaptopyrimidines [24, 42], 2-mercaptoquinazolines [43, 44], mono- and dithiophosphates [45, 46]
It was found that 2-thioxopyridines 12а, 12b react with chloride 11 in the presence of 1 equiv. of 10% aqueous KOH with the formation of previously unknown hybrid molecules 13а, 13b containing kojic acid and nicotinonitrile fragments (Scheme 2)
In the context of the known biological activity of kojic acid derivatives [7,8,9,10,11], nicotinonitriles, and quinoxalines, it seemed appropriate to perform a preliminary in silico study of possible targets, ADMET parameters, and the bioavailability criteria for new hybrid molecules

Summary

Hlg O

The analysis of literature data allows us to conclude that the reaction of halokojic acids with heterocyclic S-nucleophiles has been relatively little studied. We performed the reaction of some active S-nucleophiles of the azaheterocyclic series with chlorkojic acid 11 (Hlg = Cl). The IR spectra of compounds 13 and 15 show an absorption band at 1646–1649 cm–1, corresponding to stretching vibrations of the conjugated carbonyl group of γ-pyrone, as well as a broad band at 3226–3253 cm–1 (O–H). The spectra of compounds 13а, 13b show an absorption band in the range of 2218–2223 cm–1 (conjugated cyano group). The 1Н NMR spectra of compounds 13 and 15 exhibit singlets at 4.47–4.64 ppm (SCH2), as well as signals of the 5-hydroxypyran-4-one fragment at 6.47–6.59 (Н3), 8.01–8.09 (Н6), and 9.11– 9.15 ppm (OH). The 13C NMR spectra of compounds 13 and 15 contain characteristic

Cl O

Gastrointestinal absorption

OH O

Overall assessment of protein ligand interaction

OPEN ACCESS