US 12,233,161 B1
Lipids and lipid nanoparticle formulations
Longgui Zhang, Guangdong (CN); Yuebao Zhang, Guangdong (CN); Chen Liu, Guangdong (CN); Xiuting Xu, Guangdong (CN); Yan Wang, Guangdong (CN); Meigui Liang, Guangdong (CN); Yuanyuan Xu, Guangdong (CN); Wenting Song, Guangdong (CN); Zehao Liao, Guangdong (CN); Qinying Zhu, Guangdong (CN); and Yingxin Lu, Guangdong (CN)
Assigned to LONGUIDE BIOPHARMA CORPORATION, Guangdong (CN)
Filed by LONGUIDE BIOPHARMA CORPORATION, Guangdong (CN)
Filed on May 20, 2024, as Appl. No. 18/669,214.
Application 18/669,214 is a continuation of application No. PCT/CN2024/086718, filed on Apr. 9, 2024.
Int. Cl. A61K 9/127 (2006.01); A61K 9/51 (2006.01); A61K 31/7105 (2006.01); C07C 219/06 (2006.01); C07C 233/05 (2006.01); C07D 409/12 (2006.01)
CPC A61K 9/1271 (2013.01) [A61K 9/5123 (2013.01); A61K 31/7105 (2013.01); C07C 219/06 (2013.01); C07C 233/05 (2013.01); C07D 409/12 (2013.01)] 30 Claims
 
1. A compound of Formula I-1:

OG Complex Work Unit Chemistry
wherein:
L1 is C1-10 alkylene or C2-10 heteroalkylene; wherein the C2-10 heteroalkylene is optionally substituted with R6;
L2 is C1-10 alkylene or C2-10 heteroalkylene; wherein the C2-10 heteroalkylene is optionally substituted with R6;
X is —CH2—, —NR3—, —N(R3)2+—, —O—, —O—CH2CH2—O—, or —NR3—(CH2)m—NR3—;
m is an integer from 1 to 6;
R1, R2, and R3 are each independently hydrogen, C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, C2-20 heteroalkyl,

OG Complex Work Unit Chemistry
wherein the C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, or C2-20 heteroalkyl is independently optionally substituted with one to five halo, cyano, —OR4, —SR4, —NR42, —N(R4)3+, oxo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 haloalkyl;
each Ra is independently hydrogen, C1-12 alkyl, or —C(O)—C1-12 alkyl;
each R4 is independently hydrogen, C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl; wherein each C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl is independently optionally substituted with one to five halo, cyano, —OH, —SR5, —NR52, —N(R5)3+, or oxo;
each R5 is independently hydrogen, C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl; wherein each C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl is independently optionally substituted with one to five halo, cyano, —OH, —SH, —NH2, —NH(C1-6 alkyl), —N(C1-6 alkyl)2, —N(C1-6 alkyl)3+, or oxo;
each R6 is independently

OG Complex Work Unit Chemistry
each L is independently C1-10 alkylene or C3-10 heteroalkylene;
each Y is independently —O— or —NR7—;
each R7 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 haloalkyl;
wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 haloalkyl is independently optionally substituted with one to five halo, cyano, —OH, —NH2, —NH(C1-6 alkyl), —N(C1-6 alkyl)2, —N(C1-6 alkyl)3+, oxo, C1-6 alkoxy, or C1-6 haloalkoxy;
each n is independently an integer from 1-20;
each R is independently hydrogen, —Z—C1-20 alkyl, —Z—C2-20 alkenyl, —Z—C2-20 alkynyl, —Z-heterocyclyl, —Z1—C1-6 alkylene-Z—C1-20 alkyl, —Z1—C1-6 alkylene-Z—C2-20 alkenyl, —Z1—C1-6 alkylene-Z—C2-20 alkynyl, —Z1—C1-6 alkylene-Z-heterocyclyl, —Z1—C2-6 alkenyl-Z—C1-20 alkyl, —Z1—C2-6 alkenyl-Z—C2-20 alkenyl, —Z1—C2-6 alkenyl-Z—C2-20 alkynyl, —Z1—C2-6 alkynyl-Z—C1-20 alkyl, —Z1—C2-6 alkynyl-Z—C2-20 alkenyl, or —Z1—C2-6 alkynyl-Z—C2-20 alkynyl;
each Z is independently a bond, —O—, —NR4—, —S—, —S—S—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)NR4—, —S(O)—, —S(O)2—, —NR4C(O)—, —NR4C(O)O—, —NR4C(O)NR4—, —NR4S(O)—, or —S(O)2NR4—; and
each Z1 is independently —O—, —NR4—, —S—, —S—S—, —C(O)—, —C(O)O—, —C(O)NR4—, —S(O)—, —S(O)2—, —NR4C(O)—, —NR4C(O)O—, —NR4C(O)NR4—, —NR4S(O)—, or —S(O)2NR4—;
provided that each

OG Complex Work Unit Chemistry
moiety comprises at least 6 linear atoms.