CONJUGATES AND THEIR OBTAINING AND APPLICATION Russian patent published in 2023 - IPC C07H15/04 A61K47/50 A61P1/16 C12N15/113 

FIELD: medicinal chemistry.

SUBSTANCE: compound having the structure represented by formula (321). In the formula (321): n1 is an integer from 1 to 3, and n3 is an integer from 0 to 4; each of m1, m2 and m3 is independently an integer from 2 to 10; each of R₁₀, R₁₁, R₁₂, R₁₃, R₁₄ and R₁₅ is independently selected from H, methyl and ethyl; R₄ is a group capable of being associated with an active drug or active agent by a covalent link, where the active drug or active agent is an oligonucleotide and the bond is a phosphodiester bond; each L₁ is a connected combination of at least two of the groups A1, A4, A8, A10 and A11: where each j1 is independently an integer from 1 to 20; each j2 is independently an integer from 1 to 20; and represents the connection site of the group to the rest of the molecule; each S₁ is independently M₁ in which any active hydroxyl, if any, is protected by a hydroxyl protecting group; each M₁ is a ligand capable of binding to asialoglycoprotein receptors on the surface of liver cells (ASGPR). A conjugate, the use of a conjugate, and a method for inhibiting the expression of a particular gene in hepatocytes.

EFFECT: obtaining a conjugate that can specifically target hepatocytes, due to which it effectively solves the problems associated with the delivery of drugs based on oligonucleotides in vivo, and has low toxicity and excellent delivery efficiency, while maintaining high stability of the delivered oligonucleotide.

35 cl, 67 dwg, 24 tbl, 37 ex

Formula (321)