MODIFIED OLIGONUCLEOTIDES AND METHOD FOR PRODUCTION THEREOF Russian patent published in 2019 - IPC A61K31/712 C07H19/10 C07H19/20 C07F9/24 A61P31/12 

FIELD: chemistry.

SUBSTANCE: invention relates to nucleotides and oligonucleotides, which can be used for in vitro and in vivo studies. Disclosed is a compound of formula (I)

where Z is selected from -O^- and -S^-; R¹ is selected from -NR^1AR^1B, -OR³, -H; R² is selected from -NR^2AR^2B; R³ is selected from -C_1-10alkyl; where R^1A, R^1B, R^2A and R^2B are selected from -H, -C_1-10alkyl; or optionally R^1A and R^2A form alkylene chain with length of 2–4 atoms; optionally R^1A and R^1B or R^2A and R^2B together with atom with which they are bonded, form 5-member heterocycle; X is selected from 5'-end of nucleoside, oligonucleotide; Y is selected from 3'-end of nucleoside, oligonucleotide, -OH or -O-PG; or Y is selected from 5'-end of nucleoside, oligonucleotide, and X is selected from 3'-end of nucleoside, oligonucleotide, -OH or -O-PG; oligonucleotide contains 2–500 nucleotides, PG represents a fluorescent label or residue of a fluorescence quencher. Disclosed is oligonucleotide of 2–500 nucleotides, in which at least one internucleotide phosphate group is modified in accordance with formula FVII

where indicates point of attachment of substitutes corresponding to oligonucleotide, R¹ is selected from -NR^1AR^1B, -OR³, -H; R² is selected from -NR^2AR^2B; R³ is selected from -C_1-10alkyl; R^1A, R^1B, R^2A and R^2B are selected from -H, -C_1-10alkyl; optionally R^1A and R^2A together form alkylene chain with length of 2–4 atoms; optionally R^1A and R^1B or R^2A and R^2B together with atom with which they are bonded, form 5-member heterocycle. Disclosed is a method of producing a compound of formula (I), comprising reacting H-phosphonate, obtained according to the H-phosphonate oligonucleotide synthesis method, or phosphite, obtained according to the amidophosphite oligonucleotide synthesis method, with corresponding imino derivative of general formula HN = CR¹R² or R^Si₃SiN = CR¹R² in the presence of an oxidising agent, where R¹ and R² are given above, R^Si is alkyl or aryl. Disclosed is a method of producing a compound of formula (I), comprising a reaction of phosphite obtained according to an amidophosphite oligonucleotide synthesis method, with an organic azide selected from formulae

where the counterion is selected from Cl^-, Br^-, I^-, CF₃SO₃^-, p-toluenesulphonate C₇H₇SO₃^-, PO₂Cl₂^-, ClO₄^-, BF₄^-, BPh₄^-, PF₆^-, where R^1A, R^1B, R^2A, R^2B, R² are defined above, optionally in the presence of a silylating reagent and/or base.

EFFECT: novel oligonucleotides and methods for preparing them, which are suitable for biomedical research.

6 cl, 47 ex, 8 dwg