IONIZABLE LIPIDS AND COMPOSITIONS THEREOF IN FORM OF NANOPARTICLES Russian patent published in 2025 - IPC C07C323/26 C07C323/27 A61K9/16 A61K48/00 C12N15/86 C12N15/88 

FIELD: chemistry.

SUBSTANCE: invention relates to ionisable lipids of formula (I)

or pharmaceutically acceptable salts thereof, where R¹ and R^1’, each independently represents a linear or branched C_1-3 alkylene; R² and R^2’, each independently represents a linear or branched C_1-6 alkylene; R³ and R^3’, each independently represents a linear or branched C_1-6 alkyl; or alternatively, if R² is a branched C_1-6 alkylene, then R² and R³ together with their intermediate atom N form 4-8-membered heterocyclyl; or alternatively, if R^2' is a branched C_1-6 alkylene, then R^2' and R^3' together with their intermediate atom N form 4-8-membered heterocyclyl; R⁴ and R^4', each independently, are -CR^a, -C(R^a)₂CR^a or -[C(R^a)₂]₂CR^a; R^a for each case is independently H or C_1-3 alkyl; or alternatively, if R⁴ is C(R^a)₂CR^a or [C(R^a)₂]₂CR^a and if R^a is C_1-3 alkyl, then R³ and R⁴ together with intermediate atom N form 4-8-membered heterocyclyl; or alternatively, if R^4' is -C(R^a)₂CR^a or -[C(R^a)₂]₂CR^a and if R^a is C_1-3 alkyl, then R^3' and R^4' together with intermediate atom N form 4-8-membered heterocyclyl; R⁵ and R^5’, each independently, are C_4-20 alkyl; R⁶ and R^6' for each occurrence are independently C_1-20 alkylene, C_3-20 cycloalkylene or C_2-20 alkenylene; and m and n are each independently an integer selected from 1, 2, 3, 4 and 5, as well as to ionisable lipids selected from a group and pharmaceutically acceptable salts thereof, a lipid nanoparticle (LNP) for the delivery of a therapeutic nucleic acid, a pharmaceutical composition for delivering a transgene in the nucleic acid into the required recipient cells and the use of a lipid nanoparticle or a pharmaceutical composition for producing a drug for treating a genetic disorder in a subject.

EFFECT: lipid scaffolds are obtained, which not only demonstrate high efficiency along with reduced toxicity, but also have improved pharmacokinetics and intracellular kinetics, such as cell uptake and release of nucleic acid from a lipid carrier.

99 cl, 1 tbl, 2 ex, 19 dwg