Ionizable lipids for nucleic acid delivery

A compound, or a pharmaceutically acceptable salt thereof, of Formula (II):

• wherein:
• E1 is selected from the group consisting of —OC(O)N(Q)-δ1, —N(Q)C(O)O-δ1, —N(Q)C(O)S-δ1, and —N(Q)C(O)N(Q)-δ1;
• δ1 designates the bond linked to group R1;
• each Q is independently H or a C1-C5 alkyl;
• R1 is
• R3 and R4 are each independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
• alternatively R3 and R4 may join to form a 4-6 membered ring containing oxygen (O) or up to 2 nitrogen (N), optionally substituted with 1-2 substituents, each independently selected from the group consisting of C1-C6 alkyl, cyclopropyl, OH, and C1-C3alkoxy;
• R5 is selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and a 2-hydroxyethyl;
• R6 is selected from H and C1-C6 alkyl;
• a is 1, 2, 3, 4, or 5;
• b and c are independently 0, 1, or 2;
• c′ is 1, 2, 3, 4, or 5;
• d is 1 or 2;
• e is 0, 1, or 2;
• E2 is selected from —OC(O)-δ2, —OC(O)O-δ2, —OC(O)N(Q)-δ2, —O-δ2, —OCH2CH2O-δ2, and —OC(O)(CH2)6C(O)O-δ2;
• δ2 designates the bond linked to the R2 group;
• R2 is
• L1 and L2 are each, independently, a bond, —O-δ3, —CH2OC(O)-δ3, or —CH2O-δ3;
• δ3 designates the bond to R7 or R8;
• R7 and R8 are each independently a C4-C10 alkyl, C4-C10 alkenyl or C4-C10 alkynyl;
• f is 0, 1, 2, 3, 4, or 5;
• L3 is selected from:
• R9 is selected from H and C4-C8 alkyl;
• g is an integer from 1-18;
• and
• h is 0, 1, 2, or 3.