Lipid containing formulations
View Patent ↗Compositions and methods useful in administering nucleic acid based therapies, for example association complexes such as liposomes and lipoplexes are described.
1. A compound of formula (X)
wherein
R 1 and R 2 are each independently H, C 1 -C 6 alkyl, optionally substituted with 1-4 R 5 , C 2 -C 6 alkenyl, optionally substituted with 1-4 R 5 , or C(NR 6 )(NR 6 ) 2 ;
R 3 and R 4 are each independently alkyl, alkenyl, alkynly, each of which is optionally substituted with fluoro, chloro, bromo, or iodo;
L 1 and L 2 are each independently —NR 6 C(O)—, —C(O)NR 6 —, —S—S—, —N(R 6 )C(O)N(R 6 )—, —OC(O)N(R 6 )—, —N(R 6 )C(O)O—, —O—N═C—, OR, —OC(O)NH—N═C—, or —NHC(O)NH—N═C—, or
L 1 -R 3 and L 2 -R 4 can be taken together to form an acetal, a ketal, or an orthoester, wherein R 3 and R 4 are defined as above and can also be H or phenyl;
R 5 is fluoro, chloro, bromo, iodo, —OR 7 , —N(R 8 )(R 9 ), —CN, SR 10 , S(O)R 10 , or S(O) 2 R 10 ;
R 6 is H or C 1 -C 6 alkyl;
R 7 is H or C 1 -C 6 alkyl;
R 8 and R 9 are independently H or C 1 -C 6 alkyl;
R 10 is H or C 1 -C 6 alkyl;
m is 1, 2, 3, 4, 5, or 6;
n is 0, 1, 2, 3, 4, 5, or 6;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R 1 is H, methyl, ethyl, isopropyl, or 2-hydroxyethyl and R 2 is H, methyl, ethyl, propyl, or isopropyl.
3. The compound of claim 1 , wherein both m and n are 1.
4. The compound of claim 1 , wherein both L 1 and L 2 are —N(R 6 )C(O)N(R 6 )—.
5. The compound of claim 1 , wherein both L 1 and L 2 are —OC(O)N(R 6 )— or —N(R 6 )C(O)O—.
6. The compound of claim 1 , wherein L 1 is —NR 6 C(O)— and L 2 is —S—S—.
7. The compound of claim 1 , wherein L 1 is —OC(O)N(R 6 ) or —N(R 6 )C(O)O— and L 2 is —S—S—.
8. The compound of claim 1 , wherein L 1 is —N(R 6 )C(O)N(R 6 )— and L2 is —S—S—.
9. The compound of claim 1 , wherein L 1 -R 3 and L 2 -R 4 are taken together to form an acetal, a ketal, or an orthoester.
10. The compound of claim 1 , wherein both R 3 and R 4 are C 6 -C 28 alkyl.
11. The compound of claim 10 , wherein each L 1 and L 2 are independently —S—S—, —OC(O)N(R 6 )— or —N(R 6 )C(O)O—.
12. The compound of claim 1 , wherein each R 3 and R 4 are independently C 6 -C 30 alkenyl.
13. The compound of claim 1 , wherein at least one of R 3 and R 4 is provided in formula (II) below
wherein
x is an integer from 1 to 8; and
y is an integer from 1-10.
14. The compound of claim 1 , wherein at least one of R 1 and R 2 is provided in formula (III) below
wherein
x is an integer from 1 to 8; and
y is an integer from 1-10.
15. The compound of claim 1 , wherein at least one of R 1 and R 2 is provided in formula (IV) below
wherein
x is an integer from 1 to 8; and
y is an integer from 1-10.
16. The compound of claim 1 , wherein at least one of R 1 and R 2 is provided in formula (V) below
wherein
x is an integer from 1 to 8; and
y is an integer from 1-10.
17. A preparation comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof.
18. A compound of Formula 3
or a pharmaceutically acceptable salt thereof.
19. A preparation comprising the compound of claim 18 , or a pharmaceutically acceptable salt thereof.