Phosphatidylamine compounds including a plurality of tertiary amino group structures and compositions thereof

A lipid composition, comprising a phosphatidylamine compound including a plurality of tertiary amino group structures, wherein the phosphatidylamine compound is a compound represented by formula (I) or a stereoisomer, a prodrug, and a pharmaceutically acceptable salt thereof:

• wherein n is an integer from 0-5;
• L1 and L2 are each independently C5-C30 alkyl, C5-C40 alkenyl, or —R′-M-R″;
• R1 and R2 are each independently C4-C30 alkyl, C2-C40 alkenyl, or —R′-M-R″;
• R3 and R4 are each independently C1-C30 alkyl, C2-C40 alkenyl, or —R′-M-R″;
• or R3 is H, C1-C30 alkyl, C2-C40 alkenyl, or —R′-M-R″, and R4 is C1-C30 alkyl, C2-C40 alkenyl, or —R′-M-R″;
• R′ is C1-C24 alkylene or C2-C24 alkenylene;
• M is selected from —C(O)—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(S)—, —C(O)S—, —SC(O)—, —C(S)S—, —SC(S)—, —S(O)2—, —S—S—, —C(O)N(Ra)—, —N(Ra)C(O)—, —OC(O)N(Ra)—, —N(Ra)C(O)O—, —N(Ra)C(O)N(Ra)—, —C(O—C(O)—Ra)(H)—C1-6 alkylene-O—C(O)—, —C(O)O—C1-6 alkylene-C(O)—O—, —CH(OH)—, —P(O)(ORb)O—, C6-C10 arylene, and 5 to 10 membered heteroarylene;
• R″, Ra and Rb are each independently selected from H, C1-C30 alkyl, and C2-C40 alkenyl;
• and
• L3, L4, and L5 are each independently C1-C12 alkylene, C2-C12 alkenylene, C3-C8 cycloalkylene, -A-Y—B—, -A-Y—, or —Y—B—, wherein A and B are each independently C1-C12 alkylene or C2-C12 alkenylene, and Y is —C(OH)—, —C(O)—, —C(O)O—, —OC(O)—, — C(O)N(H)—, —N(H)C(O)—, arylene, or heteroarylene, wherein
• R1 is one of following structures, or when R2 is present, R1 and R2 are each independently one of the following structures:
• and a therapeutic agent or a prophylactic agent.

A pharmaceutical composition, comprising a phosphatidylamine compound including a plurality of tertiary amino group structures, wherein the phosphatidylamine compound is a compound represented by formula (I) or a stereoisomer, a prodrug, a pharmaceutically acceptable salt thereof:

• wherein n is an integer from 0-5;
• L1 and L2 are each independently C5-C30 alkyl, C5-C40 alkenyl, or —R′-M-R″;
• R1 and R2 are each independently C4-C30 alkyl, C2-C40 alkenyl, or —R′-M-R″;
• R3 and R4 are each independently C1-C30 alkyl, C2-C40 alkenyl, or —R′-M-R″;
• or R3 is H, C1-C30 alkyl, C2-C40 alkenyl, or —R′-M-R″, and R4 is C1-C30 alkyl, C2-C40 alkenyl, or —R′-M-R″;
• R′ is C1-C24 alkylene or C2-C24 alkenylene;
• M is selected from —C(O)—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(S)—, —C(O)S—, —SC(O)—, —C(S)S—, —SC(S)—, —S(O)2—, —S—S—, —C(O)N(Ra)—, —N(Ra)C(O)—, —OC(O)N(Ra)—, —N(Ra)C(O)O—, —N(Ra)C(O)N(Ra)—, —C(O—C(O)—Ra)(H)—C1-6 alkylene-O—C(O)—, —C(O)O—C1-6 alkylene-C(O)—O—, —CH(OH)—, —P(O)(ORb)O—, C6-C10 arylene, and 5 to 10-membered heteroarylene;
• R″, Ra, and Rb are each independently selected from H, C1-C30 alkyl, and C2-C40 alkenyl;
• and
• L3, L4, and L5 are each independently C1-C12 alkylene, C2-C12 alkenylene, C3-C8 cycloalkylene, -A-Y—B—, -A-Y—, or —Y—B—, wherein A and B are each independently C1-C12 alkylene, or C2-C12 alkenylene, and Y is —C(OH)—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)N(H)—, —N(H)C(O)—, arylene, or heteroarylene, wherein
• R1 is one of the following structures, or when R2 is present, R1 and R2 are each independently one of the following structures:
• or a lipid composition comprising the phosphatidylamine compound, a therapeutic agent or a prophylactic agent, and a pharmaceutically acceptable diluent or excipient.