US 12,404,232 B2
Compounds and compositions for intracellular delivery of therapeutic agents
Kerry E. Benenato, Cambridge, MA (US); and Mark Cornebise, Cambridge, MA (US)
Assigned to ModernaTX, Inc., Cambridge, MA (US)
Filed by ModernaTX, Inc., Cambridge, MA (US)
Filed on Nov. 30, 2021, as Appl. No. 17/538,217.
Application 17/538,217 is a continuation of application No. 16/555,045, filed on Aug. 29, 2019, granted, now 11,220,476.
Application 16/555,045 is a continuation of application No. 15/846,084, filed on Dec. 18, 2017, granted, now 10,442,756, issued on Oct. 15, 2019.
Application 15/846,084 is a continuation of application No. 15/476,253, filed on Mar. 31, 2017, granted, now 9,868,691, issued on Jan. 16, 2018.
Application 15/476,253 is a continuation of application No. PCT/US2016/052352, filed on Sep. 16, 2016.
Claims priority of provisional application 62/393,940, filed on Sep. 13, 2016.
Claims priority of provisional application 62/382,740, filed on Sep. 1, 2016.
Claims priority of provisional application 62/333,557, filed on May 9, 2016.
Claims priority of provisional application 62/266,460, filed on Dec. 11, 2015.
Claims priority of provisional application 62/253,433, filed on Nov. 10, 2015.
Claims priority of provisional application 62/252,316, filed on Nov. 6, 2015.
Claims priority of provisional application 62/220,085, filed on Sep. 17, 2015.
Claims priority of provisional application 62/220,091, filed on Sep. 17, 2015.
Prior Publication US 2022/0380299 A1, Dec. 1, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07C 229/12 (2006.01); A61K 9/00 (2006.01); A61K 9/127 (2006.01); A61K 9/1272 (2025.01); A61K 9/16 (2006.01); A61K 9/51 (2006.01); A61K 31/7105 (2006.01); A61K 38/17 (2006.01); A61K 38/18 (2006.01); A61K 47/54 (2017.01); A61K 47/69 (2017.01); A61K 48/00 (2006.01); C07C 227/16 (2006.01); C07C 227/18 (2006.01); C07C 229/16 (2006.01); C07C 233/36 (2006.01); C07C 233/72 (2006.01); C07C 235/10 (2006.01); C07C 255/24 (2006.01); C07C 263/20 (2006.01); C07C 271/20 (2006.01); C07C 275/14 (2006.01); C07C 279/12 (2006.01); C07C 279/24 (2006.01); C07C 279/28 (2006.01); C07C 279/32 (2006.01); C07C 311/05 (2006.01); C07C 335/08 (2006.01); C07D 207/27 (2006.01); C07D 233/72 (2006.01); C07D 249/04 (2006.01); C07D 263/20 (2006.01); C07D 265/33 (2006.01); C07D 271/06 (2006.01); C07D 271/10 (2006.01); C07D 277/38 (2006.01); C07F 9/09 (2006.01); C07K 14/505 (2006.01); A61K 9/1271 (2025.01)
CPC C07C 229/12 (2013.01) [A61K 9/0019 (2013.01); A61K 9/0043 (2013.01); A61K 9/0073 (2013.01); A61K 9/127 (2013.01); A61K 9/1272 (2013.01); A61K 9/1617 (2013.01); A61K 9/1641 (2013.01); A61K 9/5123 (2013.01); A61K 9/5146 (2013.01); A61K 31/7105 (2013.01); A61K 38/1725 (2013.01); A61K 38/1816 (2013.01); A61K 47/543 (2017.08); A61K 47/6911 (2017.08); A61K 48/0033 (2013.01); A61K 48/005 (2013.01); C07C 227/16 (2013.01); C07C 227/18 (2013.01); C07C 229/16 (2013.01); C07C 233/36 (2013.01); C07C 233/72 (2013.01); C07C 235/10 (2013.01); C07C 255/24 (2013.01); C07C 263/20 (2013.01); C07C 271/20 (2013.01); C07C 275/14 (2013.01); C07C 279/12 (2013.01); C07C 279/24 (2013.01); C07C 279/28 (2013.01); C07C 279/32 (2013.01); C07C 311/05 (2013.01); C07C 335/08 (2013.01); C07D 207/27 (2013.01); C07D 233/72 (2013.01); C07D 249/04 (2013.01); C07D 263/20 (2013.01); C07D 265/33 (2013.01); C07D 271/06 (2013.01); C07D 271/10 (2013.01); C07D 277/38 (2013.01); C07F 9/091 (2013.01); C07K 14/505 (2013.01); A61K 9/1271 (2013.01); A61K 48/00 (2013.01); C07C 2601/02 (2017.05); C07C 2601/04 (2017.05); C07C 2601/14 (2017.05); C07C 2601/18 (2017.05)] 15 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a salt or isomer thereof, wherein:
R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;
R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
R4 is selected from the group consisting of

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′) C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O) (OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
each R′ is independently selected from the group consisting of C4-18 alkyl, C4-18 alkenyl, —R*YR″, —YR″, and H;
each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;
each Y is independently a C3-6 carbocycle; and
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.