US 12,065,396 B2
Lipids for use in lipid nanoparticle formulations
Xinyao Du, Richmond (CA)
Assigned to Acuitas Therapeutics, Inc., Vancouver (CA)
Appl. No. 16/638,726
Filed by ACUITAS THERAPEUTICS, INC., Vancouver (CA)
PCT Filed Aug. 17, 2018, PCT No. PCT/US2018/000284
§ 371(c)(1), (2) Date Feb. 12, 2020,
PCT Pub. No. WO2019/036000, PCT Pub. Date Feb. 21, 2019.
Claims priority of provisional application 62/546,887, filed on Aug. 17, 2017.
Prior Publication US 2020/0172472 A1, Jun. 4, 2020
Int. Cl. C07C 229/24 (2006.01); A61K 9/51 (2006.01); A61K 47/14 (2017.01); C07C 233/36 (2006.01); C07C 237/06 (2006.01); C12N 15/113 (2010.01)
CPC C07C 229/24 (2013.01) [A61K 9/5123 (2013.01); A61K 47/14 (2013.01); C07C 233/36 (2013.01); C07C 237/06 (2013.01); C12N 15/113 (2013.01); C12N 2310/11 (2013.01)] 18 Claims
 
1. A compound having a structure of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein:
L1 and L2 are each independently —O(C═O)—, —(C═O)O—, —C(═O)—,—O—, —S(O)x—, —S—S—, —C(═O)S—, —SC(═O)—, —NRaC(═O)—, —C(═O)NRa—, —NRaC(═O)NRa—, —OC(═O)NRa or —NRa C(═O)O—;
G1 is C1-C2 alkylene, —(C═O)—, —O(C═O)—, —SC(═O)—, —NRaC(═O)— or a direct bond;
G2 is a direct bond;
G3 is C1-C6 alkylene;
Ra is, at each occurrence, independently H or C1-C12 alkyl;
R1a and R1b are, at each occurrence, independently either: (a) H or C1-C12 alkyl; or (b) R1a is H or C1-C12 alkyl, and R1b together with the carbon atom to which it is bound is taken together with an adjacent R1b and the carbon atom to which it is bound to form a carbon-carbon double bond;
R2a and R2b are, at each occurrence, independently either: (a) H or C1-C12 alkyl; or (b) R2a is H or C1-C12 alkyl, and R2b together with the carbon atom to which it is bound is taken together with an adjacent R2b and the carbon atom to which it is bound to form a carbon-carbon double bond;
R3a and R3b are, at each occurrence, independently either (a): H or C1-C12 alkyl; or (b) R3a is H or C1-C12 alkyl, and R3b together with the carbon atom to which it is bound is taken together with an adjacent R3b and the carbon atom to which it is bound to form a carbon-carbon double bond;
R4a and R4b are, at each occurrence, independently either: (a) H or C1-C12 alkyl; or (b) R4a is H or C1-C12 alkyl, and R4b together with the carbon atom to which it is bound is taken together with an adjacent R4b and the carbon atom to which it is bound to form a carbon-carbon double bond;
R5 and R6 are each independently H or methyl;
R7 is C1-C2 alkyl;
R8 is OH;
a and d are each independently an integer from 1 to 24;
b and c are each independently an integer from 2 to 12; and
x is 0, 1 or 2.