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US 2026/0234115 A1Published application
Lipid compounds, compositions, and uses thereof
AssigneeLiberate Bio, Inc.
InventorsGregory Lawrence HAMILTON, Can SARISOZEN, Parminder Kaur MANKOO, Stephen S. SCULLY
Life of this patent
Estimating the term…
Abstract
The present disclosure provides lipid compounds and compositions (e.g., lipid nanoparticle (LNP) compositions) comprising lipid compounds of the present disclosure. The present disclosure provides methods of delivering an active agent (e.g., polynucleotide) to a cell or tissue in a subject, preferably an extrahepatic cell or tissue, comprising administering to the subject an effective amount of a lipid nanoparticle of the present disclosure, wherein the lipid nanoparticle comprises lipid compounds of the present disclosure and the active agent (e.g., polynucleotide).
Claims121
A compound of the following formula:
- or a pharmaceutically acceptable salt thereof;
- wherein:
- each of R1 and R1′ is independently:
- (C1-C9 alkyl)-R5, (C2-C9 alkenyl)-R5, (C2-C9 alkynyl)-R5, or (C1-C8 alkoxy)-R5;
- R1″ is independently:
- (C1-C9 alkyl)-R5, (C2-C9 alkenyl)-R5, (C2-C9 alkynyl)-R5, (C1-C8 alkoxy)-R5, or R12—R3;
- each R5 is independently:
- hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C2-C12 alkoxy, optionally substituted C3-C12 cycloalkyl, optionally substituted C5-C6 aryl, 1-adamantyl, 2-adamantyl, sterolyl, C(O)O—R6, OC(O)—R6, OC(O)O—R6, CH(R7)R8, C(O)O—CH—(R7)R8, C(O)O—C1-C4 alkyl-(R9)R10, OC(O)—C1-C4 alkyl-(R9)R10, or OC(O)CH(R9)R10;
- each R6 is independently:
- C7-C12 alkyl, C7-C12 alkenyl, C7-C12 alkynyl, C7-C12 alkoxy, optionally substituted C3-C12 cycloalkyl, optionally substituted C5-C6 aryl, 1-adamantyl, 2-adamantyl, or sterolyl;
- each R7 and R8 is independently:
- C7-C12 alkyl, C7-C12 alkenyl, C7-C12 alkynyl, or C7-C12 alkoxy;
- each R9 and R10 is independently:
- C1-C12 alkyl or C2-C12 alkenyl;
- X1 is O, NH, or CHR14;
- X2 is O, NH, or CHR1;
- R2 is C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C1-C12 alkoxy, (C1-C4 alkyl)-(C1-C4 alkoxy), optionally substituted C3-C12 cycloalkyl, (C1-C4 alkyl)-(optionally substituted C3-C12 cycloalkyl), optionally substituted C3-C6 heterocycle, (C1-C4 alkyl)-(optionally substituted C3-C6 heterocycle), optionally substituted C5-C6 aryl, or (C1-C4 alkyl)-(optionally substituted C5-C6 aryl);
- R2′ is hydrogen, C1-C12 alkyl, alkenyl, or alkynyl, C1-C12 alkoxy, (C1-C4 alkyl)-(C1-C4 alkoxy);
- wherein R2 and R2′ can combine to form an optionally substituted C4-C6 cycloalkyl, an optionally substituted C3-C6 cycloalkyl, or an optionally substituted C3-C6 heterocycle;
- R3 and R4 are each independently:
- hydrogen, C1-C6 alkyl, C1-C6 alkoxy, or C1-C6 hydroxyalkyl, or wherein R3 and R4 join together to form a heterocyclic ring comprising one or more N, O, or S heteroatoms;
- R11 is hydrogen or C1-C6 alkyl, or wherein R11 and R4 join together to form a heterocyclic ring comprising one or more N, O, or S heteroatoms;
- R12 is a bond or an optionally substituted, branched or unbranched C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl;
- R13 is hydrogen, an optionally substituted C3-C12 cycloalkyl, or an optionally substituted C5-C6 aryl;
- R14 is hydrogen or C1-C6 alkyl, or wherein R14 and R2 join together to form an optionally substituted C5-C8 cycloalkyl;
- m is 1-4;
- p is 0-4;
- and
- n is 1-5.
26 more elements
A compound of the following formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- each of R1 and R1′ is independently:
- (C1-C9 alkyl)-R5, (C2-C9 alkenyl)-R5, (C2-C9 alkynyl)-R5, or (C1-C8 alkoxy)-R5;
- R1″ is independently:
- (C1-C9 alkyl)-R5, (C2-C9 alkenyl)-R5, (C2-C9 alkynyl)-R5, (C1-C8 alkoxy)-R5, or R12—R3;
- each R5 is independently:
- hydrogen, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, C2-C12 alkoxy, optionally substituted C3-C12 cycloalkyl, optionally substituted C5-C6 aryl, 1-adamantyl, 2-adamantyl, sterolyl, C(O)O—R6, OC(O)—R6, OC(O)O—R6, CH(R7)R8, C(O)O—CH(R7)R8, C(O)O—C1-C4 alkyl-(R9)R10, OC(O)—C1-C4 alkyl-(R9)R10, or OC(O)CH(R9)R10;
- each R6 is independently:
- C7-C12 alkyl, C7-C12 alkenyl, C7-C12 alkynyl, C7-C12 alkoxy, optionally substituted C3-C12 cycloalkyl, optionally substituted C5-C6 aryl, 1-adamantyl, 2-adamantyl, or sterolyl;
- each R7 and R8 is independently:
- C7-C12 alkyl, C7-C12 alkenyl, C7-C12 alkynyl, or C7-C12 alkoxy;
- each R9 and R10 is independently:
- C1-C12 alkyl or C2-C12 alkenyl;
- X1 is O, NH, or CHR14;
- X2 is O, NH, or CHR11;
- R2 is C1-C12 alkyl, C2-C12 alkenyl, or C2-C12 alkynyl, C1-C12 alkoxy, (C1-C4 alkyl)-(C1-C4 alkoxy), optionally substituted C3-C12 cycloalkyl, (C1-C4 alkyl)-(optionally substituted C3-C12 cycloalkyl), optionally substituted C3-C6 heterocycle, (C1-C4 alkyl)-(optionally substituted C3-C6 heterocycle), optionally substituted C5-C6 aryl, or (C1-C4 alkyl)-(optionally substituted C5-C6 aryl);
- R3 and R4 are each independently:
- hydrogen, C1-C6 alkyl, C1-C6 alkoxy, or C1-C6 hydroxyalkyl, or wherein R3 and R4 join together to form a heterocyclic ring comprising one or more N, O, or S heteroatoms;
- R12 is a bond or an optionally substituted, branched or unbranched C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl;
- R13 is hydrogen, an optionally substituted C3-C12 cycloalkyl, or an optionally substituted C5-C6 aryl;
- R11 is hydrogen or C1-C6 alkyl, or wherein R11 and R4 join together to form a heterocyclic ring comprising one or more N, O, or S heteroatoms;
- R14 is hydrogen or C1-C6 alkyl, or wherein R14 and R2 join together to form an optionally substituted C5-C8 cycloalkyl;
- n is 1-5;
- and
- m is 1-4.
22 more elements
The compound of 17, wherein R13 is an optionally substituted fused C3-C12 cycloalkyl, an optionally substituted bridged C3-C12 cycloalkyl, or an optionally substituted spiro C3-C12 cycloalkyl.
Dependencies are inferred from the claim text.