Constrained lipids and methods of use thereof

A compound of Formula IC:

• or a pharmaceutically acceptable salt thereof, wherein:
• A is selected from the group consisting of
• R1a is -L1-R1;
• L1 is C2-C6 alkylenyl;
• R1 is selected from the group consisting of —OH,
• R2a, R2b, and R2c are independently selected from the group consisting of hydrogen and C1-C6 alkyl;
• R3a, R3b, and R3c are independently selected from the group consisting of hydrogen and C1-C6 alkyl;
• R4a, R4b, and R4c are independently selected from the group consisting of hydrogen and C1-C6 alkyl;
• R5a, R5b, and R5c are independently selected from the group consisting of hydrogen and C1-C6 alkyl;
• R6a, R6b, and R6c are independently selected from the group consisting of hydrogen and C1-C6 alkyl;
• or
• R6a and R6b taken together with the nitrogen atom to which they are attached form a 4- to 8-membered heterocyclo;
• and R6c is selected from the group consisting of hydrogen and C1-C6 alkyl;
• R7a, R7b, and R7c are independently selected from the group consisting of hydrogen and C1-C6 alkyl;
• or
• R7a and R7b taken together with the nitrogen atom to which they are attached form a 4- to 8-membered heterocyclo;
• and R7c is selected from the group consisting of hydrogen and C1-C6 alkyl;
• R′ is hydrogen;
• R8a is -L2-R8;
• L2 is C2-C6 alkylenyl;
• R8 is selected from the group consisting of —NR9aR9b,
• R9a and R9b are independently selected from the group consisting of hydrogen and C1-C6 alkyl;
• or
• R9a and R9b taken together with the nitrogen atom to which they are attached form a 4- to 8-membered heterocyclo;
• Q1 is C1-C20 alkylenyl;
• W1 is selected from the group consisting of —C(═O)O—, —OC(═O)—, —C(═O)N(R12a)—, —N(R12a)C(═O)—, —OC(═O)N(R12a)—, —N(R12a)C(═O)O—, and —OC(═O)O—;
• R12a is selected from the group consisting of hydrogen and C1-C6 alkyl;
• X1 is optionally substituted branched C1-C15 alkylenyl;
• or
• X1 is a bond;
• Y1 is selected from the group consisting of —(CH2)m—, —O—, —S—, and —S—S—;
• m is 0, 1, 2, 3, 4, 5, or 6;
• Z1 is optionally substituted C5-C12 bridged cycloalkylenyl;
• R10 is selected from the group consisting of hydrogen, C1-C20 alkyl, and C2-C20 alkenyl;
• Q2 is C1-C20 alkylenyl;
• W2 is selected from the group consisting of —C(═O)O—, —OC(═O)—, —C(═O)N(R12b)—, —OC(═O)N(R12b)—, and —OC(═O)O—;
• R12b is selected from the group consisting of hydrogen and C1-C6 alkyl;
• X2 is optionally substituted C1-C15 alkylenyl;
• Y2 is —(CH2)n—;
• n is 0, 1, 2, 3, 4, 5, or 6;
• Z2 is —(CH2)p—;
• p is 0 or 1;
• and
• R11 is C1-C20 branched alkyl, wherein one or more methylene linkages of R11 is optionally and independently replaced with a group selected from —O—, and —CH═CH—.