AGENT FOR INHIBITING THE HUMAN TYROSYL-DNA-PHOSPHODIESTERASE 1 ENZYME BASED ON PENTAFURANOSYL NUCLEOSIDE DERIVATIVES Russian patent published in 2021 - IPC C07D307/20 C07D405/04 C07D473/30 C07D473/40 C07D473/18 C07D473/34 C07D493/04 A61K31/341 A61K31/506 A61K31/52 A61K31/522 A61P35/00 

FIELD: biology.

SUBSTANCE: invention relates to the field of molecular biology, medicinal chemistry, biochemistry, in particular to the use of pentafuranosyl nucleoside derivatives of general formula (I-II) as inhibitors of human tyrosyl-DNA phosphodiesterase 1:

where in formula (I) B = uracil-1-yl, or 5-methyluracil-1-yl (thimin-1-yl), or 5-(2-methoxycarbonylethen-1-yl)-6-methyluracil-3-yl, or 6-methyluracil-1-yl, or 4-O-methyluracil-1-yl, or 5-fluorouracil-1-yl, or 5-chlorouracil-1-yl, or 5-bromouracil-1-yl, or 5-yodouracil-1-yl, or 4-pyrimidon-1-yl, or 2-pyrimidon-1-yl, or cytosin-1-yl, or 6-chloropurin-9-yl, or 2-fluoro-6-chloropurine-9-yl, or 2,6-dichloropurin-9-yl, or hypoxanthin-9-yl, or N⁶-benzoyladenin-9-yl, or N⁶, N⁶-dibenzoyladenin-9-yl, R₁ = R₅ = H, R₂ = R₃ = R₄ = OBz (Bz-residue of benzoic acid or B = 5-iodouracil-1-yl, R₁ = R₃ = R₄ = OBz, R₂ = R₅ = H; or 1ʹ-O-α- or β-anomers or mixtures thereof , where В = ОАс (Ac-acetic acid residue R₁ = R₅ = H, R₂ = R₃ = R₄ = OBz; or 1ʹ-O-α- or β-anomers or their mixtures, where В = ОМе, R₁ = R₃ = R₄ = OBz, R₂ = R₅ = H; or 5ʹ-(R or S)-isomers or mixtures thereof, where B=uracil-3-yl, or cytosin-1-yl, or N⁶-benzoyladenin-9-yl, R₁ = H, R₂ = R₃ = R₄ = OBz, R₅ = CH₃; or B = N⁶-triphenylmethyladenin-9-yl or N²-isobutyroylguanine-9-yl, R₁ = R₅ = H, R₂ = R₃ = OH, R₄ = O-triphenylmethyl or 1ʹ-O-α- or b-anomers of 5ʹ-(R or S)-isomers or mixtures thereof, where В = ОАс or ОМе, R₁ = H, R₂ = R₃ = R₄ = OBz, R₅ = CH³ ; or B = uracil-1-yl, or 5-bromouracil-1-yl, or 5-iodouracil-1-yl, R₁ = R₅ = H, R₂, R₃ = 2ʹ, 3ʹ-O-cyclohexylidene R₄ = O-triphenylmethyl also their analogs of the L-series of the general formula (II): where B = uracil-1-yl or 5-methyluracil-1-yl (thimin-1-yl); or 1ʹ-O-α- or β-anomers or mixtures thereof, where B = OAc.

EFFECT: new use of pentafuranosyl nucleoside derivatives of general formula (I-II) as tyrosyl-DNA-phosphodiesterase inhibitors, which can be used for combined antitumor therapy, is proposed.

1 cl, 4 dwg, 1 tbl, 20 ex