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US 12,636,368 B2Granted
Ionizable lipids for nucleic acid delivery
AssigneeGlobal Life Sciences Solutions Canada ULC
InventorsAnitha Thomas, Nikita Jain, Andrew William Brown
Life of this patent
Estimating the term…
Abstract
The present document describes compounds, or pharmaceutically acceptable salt thereof, of a core formula (I) Wherein R1 includes an amino group. These compounds are particularly useful in the formulation and in vivo and ex vivo delivery of nucleic acid and protein therapeutics for preparing and implementing T cell transfection, gene editing, cancer therapies, cancer prophylactics, and in the preparation of vaccines.
Claims23
A compound, or a pharmaceutically acceptable salt thereof, of formula (II):
- wherein E1 is selected from the group consisting of —O-δ1, —OC(O)O-δ1, —OC(O)-δ1, —OC(O)N(Q)-δ1, —OC(O)S-δ1, —C(O)N(Q)-δ1, —C(O)O-δ1, —N(Q)C(O)-δ1, —N(Q)C(O)O-δ1, —N(Q)C(O)S-δ1, and —N(Q)C(O)N(Q)-δ1;
- Q is H or a C1-C5 alkyl;
- δ1 designates the bond linked to R1;
- R1 is selected from the group consisting of:
- wherein:
- R3 and R4 are each independently selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
- alternatively R3 and R4 may join to form a 4-6 membered ring containing oxygen (O) or up to 2 nitrogen (N), optionally substituted with 1-2 substituents, each independently selected from the group consisting of C1-C6 alkyl, cyclopropyl, OH, and C1-C3 alkoxy;
- R5 is selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, and 2-hydroxyethyl;
- R6 is H or a C1-C6 alkyl;
- a is 1, 2, 3, 4 or 5;
- b and c are independently 0, 1, or 2;
- c′ is 1, 2, 3, 4, or 5;
- d is 1 or 2;
- e is 0, 1, or 2;
- each of E2 is selected from the group consisting of —OC(O)-δ2, —OC(O)O-δ2, —OC(O)N(Q)-δ2, —O-δ2, —OCH2CH2O-δ2, and —OC(O)(CH2)6C(O)O-δ2;
- Q is H or a C1-C5 alkyl;
- δ2 designates the bond linked to R2;
- R2 is
- or has the formula —(CH2)g-[L3-(CH2)]h—R9, wherein:
- L1 and L2 are each, independently, a direct bond, —O-δ3, —CH2OC(O)-δ3, or —CH2O-δ3;
- δ3 designates the bond linked to the respective one of R7 and R8;
- R7 and R8 are each independently a C4-C10 alkyl, a C4-C10 alkenyl or a C4-C10 alkynyl;
- f is 0, 1, 2, 3, 4, or 5;
- L3 is selected from the group consisting of
- R9 is H or a C4-C8 alkyl;
- g is an integer in the range of 1-18;
- and
- h is 0, 1, 2, or 3.
25 more elements
A compound, or a pharmaceutically acceptable salt thereof, of formula (II)
- wherein E1 is selected from the group consisting of —OC(O)O-δ1, —OC(O)-δ1, —OC(O)N(Q)-δ1, and —OC(O)S-δ1;
- Q is H or a C1-C5 alkyl;
- and δ1 designates the bond linked to R1;
- R1 is selected from the group consisting of:
- wherein:
- R3 and R4 are each independently selected from C1-C6 alkyl;
- alternatively R3 and R4 may join to form a 5-6 membered ring containing up to 2 nitrogen (N), optionally substituted with 1-2 substituents, each independently selected from C1-C6 alkyl;
- R5 is a C1-C6 alkyl or a C3-C6 cycloalkyl;
- R6 is an H or a C1-C6 alkyl;
- a is 1, 2, 3, or 4;
- b and c are independently 0, 1, or 2;
- c′ is 2, 3, or 4;
- d is 2;
- e is 0 or 1;
- each of E2 is selected from the group consisting of —O-δ2, —OC(O)-δ2, —OCH2CH2O-δ2, and —OC(O)(CH2) 6C(O)O-δ2;
- where δ2 designates the bond linked to R2;
- R2 is
- or has the formula —(CH2)g-[L3-(CH2)]h—R9, wherein:
- L1 and L2 are each, independently, a direct bond, —O-δ3, —CH2OC(O)-δ3, or —CH2O-δ3;
- δ3 designates the bond linked to the respective one of R7 and R8;
- R7 and R8 are each independently a C4-C10 alkyl, a C4-C10 alkenyl or a C4-C10 alkynyl;
- f is 0, 1, 2, 3, 4, or 5;
- L3 is selected from the group consisting of
- R9 is H or a C4-C8 alkyl;
- g is an integer in the range of 1-18;
- and
- h is 0, 1, or 2.
24 more elements
A compound, or a pharmaceutically acceptable salt thereof, of formula (II)
- wherein E1 is selected from the group consisting of —OC(O)O-δ1, —OC(O)-δ1, —OC(O)N(Q)-δ1, and —OC(O)S-δ1;
- Q is H or a C1-C5 alkyl;
- and δ1 designates the bond linked to R1;
- R1 is selected from the group consisting of:
- wherein:
- R3 and R4 are each independently selected from C1-C6 alkyl;
- alternatively R3 and R4 may join to form a 5-6 membered ring containing up to 2 nitrogen (N), optionally substituted with 1-2 substituents, each independently selected from C1-C6 alkyl;
- R5 is a C1-C6 alkyl or cyclopropyl;
- R6 is H or a C1-C6 alkyl;
- a is 1, 2, 3, or 4;
- b is 0 or 1;
- c is 0, 1, or 2;
- c′ is 2, 3, or 4;
- d is 2;
- e is 1;
- each of E2 is selected from the group consisting of —O-δ2, —OC(O)-δ2, —OCH2CH2O-δ2, and —OC(O)(CH2) 6C(O)O-δ2;
- where δ2 designates the bond linked to R2;
- R2 is
- or has the formula —(CH2)g-[L3-(CH2)]h—R9, wherein:
- L1 and L2 are each a direct bond;
- R7 and R8 are each independently selected from C4-C10 alkyl;
- f is 0 or 1;
- L3 is selected from the group consisting of
- R9 is H or a C4-C8 alkyl;
- g is an integer in the range of 1-18;
- and
- h is 0, 1, or 2.
24 more elements
A compound, or a pharmaceutically acceptable salt thereof, of formula (III)
- wherein R1 is selected from the group consisting of:
- wherein:
- R3 and R4 are each independently selected from C1-C6 alkyl;
- alternatively R3 and R4 may join to form a 5-6 membered ring containing up to 2 nitrogen (N), optionally substituted with 1-2 substituents, each independently selected from C1-C6 alkyl;
- R5 is a C1-C6 alkyl or cyclopropyl;
- R6 is H or a C1-C6 alkyl;
- a is 1, 2, 3, or 4;
- b is 0 or 1;
- c is 0, 1, or 2;
- c′ is 2, 3, or 4;
- dis 2;
- e is 1;
- each of E2 is selected from the group consisting of —O-δ2, —OC(O)-δ2, —OCH2CH2O-δ2, and —OC(O)(CH2) 6C(O)O-δ2;
- where δ2 designates the bond linked to R2;
- R2 is
- or has the formula —(CH2)g-[L3-(CH2)]h—R9, wherein:
- L1 and L2 are each a direct bond;
- R7 and R8 are each independently selected from C4-C10 alkyl;
- f is 0 or 1;
- L3 is selected from the group consisting of
- R9 is H or a C4-C8 alkyl;
- g is an integer in the range of 1-18;
- and
- h is 0, 1, or 2.
21 more elements
A compound according to any one of the following structures:
- or a pharmaceutically acceptable salt thereof.
A compound according to any one of the following structures:
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.