Tricine and citric acid-based cationic lipids with aromatic head groups
AssigneeSanofi
InventorsSaswata KARMAKAR, Apiwat WANGWEERAWONG
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Abstract
The present invention provides, in part, tricene and citric acid-based cationic lipids with aromatic head groups of Formula (I), and sub-formulas thereof: or a pharmaceutically acceptable salt thereof. The compounds 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.
Claims19
A cationic lipid having a structure according to Formula (I):
- or a pharmaceutically acceptable salt thereof,
- wherein is selected from optionally substituted arylene or optionally substituted heteroarylene;
- wherein L2 is selected from a bond, optionally substituted (C1-C6) alkylene or optionally substituted (C2-C6) alkenylene;
- wherein X1 is O;
- wherein R1 is
- wherein a is selected from 0, 1, 2, 3, 4 or 5;
- wherein R2 and R3 are each independently selected from H or optionally substituted (C1-C6)alkyl;
- wherein R4 and R5 are each independently selected from H, or optionally substituted (C1-C6)alkyl;
- wherein L1 is selected from D or E-L3C(═O)O— wherein the right hand side of the recited structure is bound to the ;
- wherein D is selected from —(C1-C3)alkyl-O—, —OC(═O)O—, —SC(═O)O—, —OC(═O)S—, —(C1-C3)alkyl-OC(═O)O—, or —C(═O)O—, wherein the right hand side of each recited structure is bound to the ;
- wherein E is selected from —OC(═O)—, or —(C1-C3)alkyl-OC(═O)—, wherein the right hand side of each recited structure is bound to the L3;
- wherein L3 is selected from optionally substituted (C1-C6)alkylene, or optionally substituted (C2-C6)alkenylene;
- wherein each n is independently selected from 0 or 1;
- wherein Y is selected from hydrogen, optionally substituted (C1-C6) alkyl, optionally substituted (C2-C6) alkenyl, optionally substituted (C2-C6) alkynyl, or
- wherein Z is selected from
- wherein one of X2A and X2B is O and the other is a covalent bond;
- wherein one of X3A and X3B is O and the other is a covalent bond;
- wherein one of X4A and X4B is O and the other is a covalent bond;
- wherein one of X5A and X5B is O and the other is a covalent bond;
- and
- wherein R6, R7, R8 and R9 are each independently selected from optionally substituted (C6-C30) alkyl, optionally substituted (C6-C30) alkenyl, optionally substituted (C6-C30) alkynyl, or optionally substituted (C6-C15) alkenylene-S—S-optionally substituted (C6-C15) alkyl.
A compound selected from those listed in Table A or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.