Ionizable lipid compounds

A compound of formula (IV), or a pharmaceutically acceptable salt, isotopic variant, tautomer or stereoisomer thereof:

• wherein,
• M1 and M2 are independently selected from —(O)O—, —OC(O)O—, —OC(O)—, —SC(O)—, —C(O)S—, —C(O)NRa—, and —NRaC(O)—;
• Q is —C(O)O—;
• G5 is a chemical bond;
• G6a and G6b are independently a chemical bond or C1-7 alkylene;
• G6a and G6b have a total length of 0, 1, 2, 3, 4, 5, 6 or 7 carbon atoms;
• R9 and R10 are independently H or C1-8 alkyl;
• G1, G2, G3 and G4 are independently a chemical bond, C1-13 alkylene, C2-13 alkenylene or C2-13 alkynylene, which is optionally substituted with one or more Rs;
• G1 and G2 have a total length of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 carbon atoms;
• G3 and G4 have a total length of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 carbon atoms;
• R3 and R4 are independently H, C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3- to 14-membered cycloalkyl, 3- to 14-membered heterocyclyl, C6-10 aryl or 5- to 14-membered heteroaryl, which is optionally substituted with one or more R*:
• or, R3 and R4 are taken together with the N atom to which they are attached to form 3- to 14-membered heterocyclyl, which is optionally substituted with one or more R*;
• or, R4 and Ro are taken together with the atoms to which they are attached to form 3- to 14-membered heterocyclyl or 5- to 14-membered heteroaryl, which is optionally substituted with one or more R*;
• R* is independently H, halogen, cyano, C1-10 alkyl, C1-10 haloalkyl, -Lb-ORb, -Lb-SRb or -Lb-NRbR′b;
• R5, R6, R7 and R8 are independently C1-2 alkyl;
• R1 and R2 are independently C4-20 alkyl, C4-20 alkenyl or C4-20 alkynyl, which is optionally substituted with one or more R, and wherein one or more methylene units are optionally and independently replaced with —NR″—;
• Rs is independently H, C1-14 alkyl, -Ld-ORd, -Ld-SRd or -Ld-NRdR′d;
• R is independently H, C1-20 alkyl, -La-ORa, -La-SRa or -La-NRaR′a;
• R″ is independently H or C1-20 alkyl;
• La and Le are independently a chemical bond or C1-20 alkylene;
• Lb and Lf are independently a chemical bond or C1-10 alkylene;
• Ld is independently a chemical bond or C1-14 alkylene;
• Ra and R′a are independently H, C1-20 alkyl, 3- to 14-membered cycloalkyl, and 3- to 14-membered heterocyclyl, which are optionally substituted with one or more of the following substituents:
• H, C1-20 alkyl, -Le-ORe, -Le-SRe and -Le-NReR′e;
• Rb and R′b are independently selected from H, C1-10 alkyl, 3- to 14-membered cycloalkyl, and 3- to 14-membered heterocyclyl, which are optionally substituted with one or more of the following substituents:
• H, C1-10 alkyl, -Lf-ORf, -Lf-SRf and -Lf-NRfR′f,
• Rd and R′d are independently H or C1-14 alkyl;
• Re and R′e are independently H or C1-20 alkyl;
• Rf and R′f are independently H or C1-10 alkyl.