Low molecular weight cyclic amine containing cationic lipids for oligonucleotide delivery

摘要

The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids comprising at least one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

主权项

1. A cationic lipid of Formula A: wherein: R1 is selected from H, and (C1-C6)alkyl, wherein said alkyl are optionally substituted with one to three substituents selected from R″; n and m are 1; X is O; L1 is C12-C24 alkenyl, said alkenyl are optionally substituted with one or more substituents selected from R″; and L2 is selected from C3-C9 alkyl said alkyl are optionally substituted with one or more substituents selected from R″; R″ is independently selected from H and (C1-C6)alkyl; or any pharmaceutically acceptable salt or stereoisomer thereof.