Amino lipid compound and lipid nanoparticle for delivering bioactive ingredient

An amino lipid compound having a structure of formula (Va):

• or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof,
• wherein:
• A1, A2, and A3 are one of the following:
• (1) when the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are absent, A1 is C1-C5 hydrocarbyl or C1-C5 heterohydrocarbyl, A2 is C1-C5 hydrocarbyl or C1-C5 heterohydrocarbyl, and A3 is C1-C5 hydrocarbylene or a bond;
• (2) when the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 is C1-C3 hydrocarbylene or C1-C3 heterohydrocarbylene, A2 is C1-C3 hydrocarbylene or C1-C3 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene or a bond, and A1 and A2, together with the nitrogen atom to which they are both attached, form a four-, five-, or six-membered ring;
• or
• (3) when the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is C1-C3 hydrocarbylene or C1-C3 heterohydrocarbylene, A2 is C1-C5 hydrocarbyl or C1-C5 heterohydrocarbyl, A3 is C1-C5 hydrocarbylene, and A1 and A3, together with the nitrogen atom to which they are both attached, form a four-, five-, or six-membered ring;
• A4 is C1-C5 hydrocarbylene or a bond;
• A5 is C1-C16 hydrocarbylene or a bond;
• A6 is C1-C16 hydrocarbylene or a bond;
• A2 is C1-C18 hydrocarbylene or a bond;
• A8 is C1-C18 hydrocarbylene or a bond;
• R9 is C1-C18 hydrocarbyl, or C1-C18 heterohydrocarbyl containing O or S;
• and
• R11 is C1-C18 hydrocarbyl, or C1-C18 heterohydrocarbyl containing O or S.

An amino lipid compound having a structure of formula (II-Va):

• or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof,
• wherein:
• A1, A2, and A3 are one of the following:
• (1) when the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are absent, A1 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, A2 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, and A3 is C1-C5 hydrocarbylene or a bond;
• (2) when the dashed line connecting A1 and A2 is a bond and the dashed line connecting A1 and A3 is absent, A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene or a bond, and A1 and A2, together with the nitrogen atom to which they are both attached, form an N-containing heterocyclic ring;
• (3) when the dashed line connecting A1 and A3 is a bond and the dashed line connecting A1 and A2 is absent, A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is H, C1-C5 hydrocarbyl, or C1-C5 heterohydrocarbyl, A3 is C1-C5 hydrocarbylene, and A1 and A3, together with the nitrogen atom to which they are both attached, form an N-containing heterocyclic ring;
• or
• (4) when the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are a bond, A1 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A2 is C1-C5 hydrocarbylene or C1-C5 heterohydrocarbylene, A3 is C1-C5 hydrocarbylene, and A1, A2 and A3, together with the nitrogen atom to which they are all attached, form an N-containing spiro-, fused, or bridged heterocyclic ring;
• A4 is a bond;
• A5 and A6 are each independently C3, C4, C5, or C6 alkenylene;
• or each independently C7, C8, C9, or C10 alkenylene;
• A7 and A8 are each independently C1-C18 hydrocarbylene or a bond;
• A12 is a bond;
• and
• R9 and R11 are each independently C1-C24 hydrocarbyl, or C1-C24 heterohydrocarbyl containing O or S.

An amino lipid compound having a structure of formula (II-VIa-c):

• or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof,
• wherein:
• Z1 and Z2 are —C(═O)O—;
• A4 is a bond;
• A5 and A6 are each independently C3-C10 alkylene;
• A7 and A8 are each independently C2-C4 alkylene;
• each R9 is independently C3-C9 alkyl;
• each R is independently C3-C9 alkyl;
• and
• the dashed line connecting A1 and A2 and the dashed line connecting A1 and A3 are absent, A1 and A2 are each independently C1-C3 alkyl, and A3 is C2-C4 alkylene.