Ionizable lipids and compositions comprising same

A compound represented by Formula 3:

• wherein A represents a 5-membered heteroaryl, 5-membered cycloalkyl optionally comprising an unsaturated bond, or a 5-membered heterocyclyl optionally comprising an unsaturated bond, or by Formula 1:
• or Formula 2:
• or by Formula 4:
• wherein each X1 independently comprises CH, CH2, CHR2, CHR1, NR1, NR2, NH, N, O, or S;
• or by Formula 5:
• wherein Z represents (i) an optionally substituted bicyclic aliphatic ring optionally comprising between 1 and 4 X1, or (ii) an optionally substituted bicyclic ring optionally comprising between 1 and 4 X1, wherein at least one ring is aromatic,
• or by Formula 6:
• wherein each R independently comprises any of:
• wherein k,
• and y, are integers each independently being between 1 and 10;
• n and m are integers each independently being between 0 and 10;
• each X independently comprises CH2, CHR2, CHR1, C(R2)2, C(R1)2, NR1, NR2, NH, O, S, or is absent;
• X′ represents CH2, CHR2, CHR1, O, S, —CONH(R′), —CON(R′)2, —CO2R′, —OCOR′, —OC(═O)O—, —OC(═O)NR′, —OC(═S)OR′, —OC(═S)NR′, —SO2—, —SO—, —SO2O—, —SO2NR′;
• each L independently is absent, or represents a (C1-C5) alkyl, an ester, a carbonyl, an amide, CHR1, C(R1)2, NR1, NH, O, S, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), hydroxy(C1-C6 alkoxy), alkoxy(C1-C6 alkyl), alkoxy(C1-C6 alkoxy), C1-C6 alkyl-NR′2, C1-C6 alkyl-SR′, —CONH(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —CO2—, —CO2R′, —OCO—, —OCOR′, —OC(═O)O—, —OC(═O)NR′, —OC(═S)OR′, —OC(═S)NR′, —SO2—, —SO—, —SO2O—, —SO2NR′, or any combination thereof as allowed by valency;
• wherein each R1 is H or independently comprises (i) a C1-C30 alkyl, (ii) a C1-C30 alkenyl, (ii) a C1-C30 alkynyl, each of (i), (ii) and (iii) optionally comprising one or more heteroatoms;
• and wherein each R2 is independently absent, or represents one or more substituents selected from hydrogen, halogen, —NO2, —CN, —OH, oxo, imino, —CONH2, —CONR′2, —CNNR′2, —CSNR′2, —CONH—OH, —CONH—NH2, NHCOR′, —NHCSR′, —NHCNR′, —NC(═O)OR, —NC(═O)NR′, —NC(═S)OR′, —NC(═S)NR′, —SO2R′, —SOR′, —SR′, —SO2OR′, —SO2N(R′)2, —NHNR′2, —NNR′, C1-C6 haloalkyl, optionally substituted C1-C6 alkyl, —NH2, —NR′2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), hydroxy(C1-C6 alkoxy), alkoxy(C1-C6 alkyl), alkoxy(C1-C6 alkoxy), C1-C6 alkyl-NR′2, C1-C6 alkyl-SR′, —CONH(C1-C6 alkyl), —CON(C1-C6 alkyl)2, —CO2H, —CO2R′, —OCOR, —OCOR′, —OC(═O)OR′, —OC(═O)NR′, —OC(═S)OR′, —OC(═S)NR′, or a combination thereof;
• wherein each R′ independently represents hydrogen, or is selected from the group comprising optionally substituted C1-C10 alkyl, optionally substituted C1-C30 alkyl, optionally substituted C1-C30 alkenyl, optionally substituted C1-C30 alkynyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C3-C10 heterocyclyl, optionally substituted heteroaryl, optionally substituted aryl, hydroxy, amino, —NH2, —NR′2—NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkoxy, C1-C6 haloalkoxy, hydroxy(C1-C6 alkyl), hydroxy(C1-C6 alkoxy), alkoxy(C1-C6 alkyl), alkoxy(C1-C6 alkoxy), C1-C6 alkyl-NR′2, C1-C6 alkyl-SR′, or a combination thereof.