Tricine and citric acid lipids
AssigneeTranslate Bio, Inc.
InventorsShrirang Karve, Frank DeRosa
Life of this patent
Estimating the term…
Abstract
Disclosed are cationic lipids which are compounds of Formula (A). Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.
Claims20
A cationic lipid having a structure according to Formula (A):
- or a pharmaceutically acceptable salt thereof, wherein
- each n is independently 0 or 1;
- X1A is O or NR1A,
- R1A is H or C1-C6 alkyl;
- X1B is a covalent bond, C(O), CH2CO2, or CH2C(O);
- one of X2A and X2B is O and the other is a covalent bond;
- one of X3A and X3B is O and the other is a covalent bond;
- one of X4A and X4B is O and the other is a covalent bond;
- R1 is L1-B1;
- unsubstituted linear or branched C6-C30 alkyl, C6-C30 alkenyl, or C6-C30 alkynyl or linear C6-C12 alkyl, C6-C12 alkenyl, or C6-C12 alkynyl substituted with —O(CO)R5 or —C(O)OR5;
- R2 is L2-B2;
- unsubstituted linear or branched C6-C30 alkyl, C6-C30 alkenyl, or C6-C30 alkynyl or linear C6-C12 alkyl, C6-C12 alkenyl, or C6-C12 alkynyl substituted with —O(CO)R5 or —C(O)OR5;
- R3 is L3-B3;
- unsubstituted linear or branched C6-C30 alkyl, C6-C30 alkenyl, or C6-C30 alkynyl or linear C6-C12 alkyl, C6-C12 alkenyl, or C6-C12 alkynyl substituted with —O(CO)R5 or —C(O)OR5;
- R4 is L4-B4;
- unsubstituted linear or branched C6-C30 alkyl, C6-C30 alkenyl, or C6-C30 alkynyl or linear C6-C12 alkyl, C6-C12 alkenyl, or C6-C12 alkynyl substituted with —O(CO)R5 or —C(O)OR5;
- L1, L2, L3, and L4 are each independently unsubstituted C1-C30 alkylene, C2-C30 alkenylene, or C2-C30 alkynylene;
- each R5 is independently unsubstituted C6-C14 alkyl;
- each of B1, B2, B3, and B4 is independently NH2, guanidine, amidine, a mono- or dialkylamine, 5- to 6-membered nitrogen-containing heterocycloalkyl, or 5- to 6-membered nitrogen-containing heteroaryl,
- and
- wherein the cationic lipid comprises at least one of B1, B2, B3, and B4.
A cationic lipid that is any one of Compounds 1-264, Ia-Ih, IIb1-IIb4, IIc1-IIc4, IIIa-IIId, and Va-Vd, or a pharmaceutically acceptable salt thereof.
A cationic lipid selected from the group consisting of:
- or a pharmaceutically acceptable salt thereof.
A cationic lipid having a structure according to Formula (IIa),
- or a pharmaceutically acceptable salt thereof,
- wherein
- R1A is H or C(O)—R7,
- L1 is unsubstituted C1-C10 alkylene,
- B1 is NH2, guanidine, amidine, a mono- or dialkylamine, 5- to 6-membered nitrogen-containing heterocycloalkyl, or 5- to 6-membered nitrogen-containing heteroaryl
- each of R2, R3, R4, and R7 is independently unsubstituted linear or branched C6-C30 alkyl, C6-C30 alkenyl, or C6-C30 alkynyl;
- or linear C6-C12 alkyl, C6-C12 alkenyl, or C6-C12 alkynyl substituted with —O(CO)R5 or —C(O)OR5, and
- each R5 is independently unsubstituted C6-C14 alkyl.
A cationic lipid having a structure according to Formula (A):
- or a pharmaceutically acceptable salt thereof, wherein
- each n is independently 0 or 1;
- X1A is O or NR1A,
- R1A is H or C1-C6 alkyl;
- X1B is a covalent bond, C(O), CH2CO2, or CH2C(O);
- one of X2A and X2B is O and the other is a covalent bond;
- one of X3A and X3B is O and the other is a covalent bond;
- one of X4A and X4B is O and the other is a covalent bond;
- R1 is L1B1;
- L1 is C1-C30 alkylene, C2-C30 alkenylene, or C2-C30 alkynylene;
- B1 is NH2, guanidine, amidine, a mono- or dialkylamine, 5- to 6-membered nitrogen-containing heterocycloalkyl, or 5- to 6-membered nitrogen-containing heteroaryl,
- and
- each of R2, R3, and R4 is independently:
Dependencies are inferred from the claim text.