US 12,440,569 B2
Ionizable lipids and compositions for nucleic acid delivery
Xiangrong Song, Chengdu (CN); Xiawei Wei, Chengdu Tianfu International Bio-Town (CN); and Yuquan Wei, Chengdu Tianfu International Bio-Town (CN)
Assigned to WESTGENE BIOPHARMA CO., LTD, Tianfu International Bio-Town (CN)
Filed by WESTGENE BIOPHARMA CO., LTD, Tianfu International Bio-Town (CN)
Filed on Nov. 6, 2023, as Appl. No. 18/387,296.
Application 18/387,296 is a continuation of application No. 18/117,049, filed on Mar. 3, 2023, granted, now 11,839,657.
Application 18/117,049 is a continuation of application No. PCT/CN2022/086310, filed on Apr. 12, 2022.
Claims priority of application No. 202110396368.4 (CN), filed on Apr. 13, 2021.
Prior Publication US 2024/0100167 A1, Mar. 28, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/54 (2017.01); A61K 9/51 (2006.01); A61K 39/215 (2006.01); A61K 47/24 (2006.01); A61K 47/28 (2006.01); A61K 47/60 (2017.01); C07C 229/12 (2006.01); C07C 237/06 (2006.01); C07C 271/20 (2006.01); C07C 323/25 (2006.01); A61K 39/00 (2006.01)
CPC A61K 47/543 (2017.08) [A61K 9/5123 (2013.01); A61K 39/215 (2013.01); A61K 47/24 (2013.01); A61K 47/28 (2013.01); A61K 47/60 (2017.08); C07C 229/12 (2013.01); C07C 237/06 (2013.01); C07C 271/20 (2013.01); C07C 323/25 (2013.01); A61K 2039/6018 (2013.01)] 19 Claims
 
1. A compound of Formula (I-1):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
m1, m2, m3, and m4 are the same, all of which are 1, 2, 3, 4, or 5;
L1, L2, L3, and L4 are the same, all of which are selected from —CH(OH)—, —C(═O)—,  —C(═O)O—  ,  —OC(═O)—  ,  —C(═O)NRa—  ,  —NRaC(═O)—  , or absent, wherein
 — represents the point which attaches to R1-4; —  represents the point which attaches to —(CH2)m1-m4—; and
each Ra is independently —H or optionally substituted C1-C6 alkyl;
R1, R2, R3, and R4 are the same, all of which are selected from optionally substituted C6-C18 alkyl, or optionally substituted C6-C18 alkenyl;
G1 and G2 are the same, and G3 and G4 are the same, when G1 and G2 are —Rc—, G3 and G4 are selected from —Rc—, *—RcC(═O)Rd—**, *—RcC(═O)ORd—**, *—RcOC(═O)Rd—**, *—RcC(═O)N(Rb)Rd—**, *—RN(Rb)C(═O)Rd—**, or absent; wherein
*— represents the point which attaches to the —CH2— group next to the terminal tertiary amine atom as shown in Formula (I-1); —** represents the point which attaches to the —CH2— group next to the middle tertiary amine atom as shown in Formula (I-1);
when G3 and G4 are —Rc—, G1 and G2 are selected from —Rc—, #—RcC(═O)Rd—##, #—RcC(═O)ORd—##, #—RcOC(═O)Rd—##, #—RcC(═O)N(Rb)Rd—##, #—RN(Rb)C(═O)Rd-##, #—RcN(Rb)C(═O)ORd—##, #—RcOC(═O)N(Rb)Rd—##, or absent;
wherein
#— represents the point which attaches to the —CH2— group next to the middle tertiary amine atom as shown in Formula (1-1); —## represents the point connecting G1 and G2; and
each Rb is independently —H or optionally substituted C1-C6 alkyl;
each Rc and Rd are independently —(CH2)n—, and n is 0, 1, 2, 3, or 4;
R5 and R6 are the same, both of which are selected from-H or optionally substituted C1-C4 alkyl.