SUBSTITUTED 3,4,12,12A-TETRAHYDRO-1H-[1,4]OXAZINO[3,4-C]PYRIDO[2,1-F][1,2,4]TRIAZINE-6,8-DIONE, PHARMACEUTICAL COMPOSITION, METHODS FOR PRODUCTION AND USE THEREOF Russian patent published in 2020 - IPC C07D498/14 A61K31/5383 A61P31/16 

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound which is substituted 3,4,12,12a-tetrahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-ƒ][1,2,4]triazine-6,8-dione of general formula 1 and its stereoisomer. Compounds have high antiviral activity and can be used as an effective agent for preventing and treating viral diseases, including influenza. In general formula 1

R¹ is 6,7-difluoro-5,10-dihydrothieno[3,2-c][2]benzothiepin-10-yl,(3,4-difluorophenyl)(phenyl)methyl, (3,4-difluorophenyl)(2-methylsulphanylphenyl)methyl, diphenylmethyl, bis(4-fluorophenyl)methyl, R² denotes hydrogen, benzyl or {[(C₁-C₃ alkyl)oxycarbonyl]-oxy}methyl. Compound of formula 1 is obtained by reacting (12aR)-7-(benzyloxy)-3,4,12,12a-tetrahydro-1H-[1,4]oxazino[3,4-c]-pyrido[2,1-f][1,2,4]triazine-6,8-dione (2) with 6,7-difluoro-5,10-dihydrothieno[3,2-c][2]benzothiepin-10-ol (3), or with (3,4-difluorophenyl) (phenyl) methanol (5), or with (3,4-difluorophenyl)(2-methylsulphanylphenyl)methanol (6), or with diphenylmethanol (7), or with bis(4-fluorophenyl) methanol (8):

to obtain corresponding benzyloxy compounds, further if necessary debenzylation thereof in dimethylsulphoxide in the presence of LiCl or in acetonitrile in the presence of MgBr₂⋅Et₂O to obtain compounds, where R² denotes H, followed by, if necessary, acylation of the obtained compounds with chloromethyl methylcarbonate in dimethylacetamide in the presence of potassium iodide and potassium carbonate to obtain the corresponding methyl-methylcarbonates.

EFFECT: compounds of formula 1 exhibit higher activity than the known antiviral compound, having the trade name Xofluza, used for treating influenza A and B infection.

17 cl, 5 tbl, 25 ex, 3 dwg