Aromatic ionizable cationic lipid
What is described is a compound of formula I wherein X is an ethene, or an unsubstituted or substituted arene or heteroarene; Y is a bond, an ethene, or an unsubstituted or substituted arene or heteroarene; Z is S or O; L is a linear or branched alkylene of 1 to 6 carbons; R 1 and R 2 are independently a linear or branched alkyl or alkenyl of 1 to 18 carbons; R 3 and R 4 are independently a linear or branched alkyl of 1 to 6 carbons; n is 0 to 6; and m, p, q, and r are independently 1-18; or a pharmaceutically acceptable salt thereof.
1. A compound of formula I
wherein
X is a bond, linear or branched alkylene, alkenylene, or monocyclic, bicyclic, or tricyclic arene or heteroarene;
Y is a monocyclic, bicyclic, or tricyclic arene or heteroarene;
Z is S or O;
L is a linear or branched alkylene of 1 to 6 carbons;
R 3 and R 4 are independently a linear or branched alkyl of 1 to 6 carbons;
R 1 and R 2 are independently a linear or branched alkyl or alkenyl of 1 to 20 carbons;
r is 0 to 6; and
m, n, p, and q are independently 1 to 18;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R1 is methyl, X is a bond, and m+n=6 to 20.
3. The compound of claim 2 , wherein m+n=8.
4. The compound of claim 1 , wherein the arene or heteroarene is selected from the group consisting furan, benzofuran, isobenzofuran, pyrrole, indole, isoindole, thiophene, benzothiophene, benzo[c]thiophene, imidazole, benzimidazole, purine, pyrazole, indazol, oxazole, benzoxazole, isoxazole, benzisoxazole, thiazole, isothiazole, benzothiazole, benzene, naphthalene, anthracene, pyridine, quinolone, isoquinoline, pyrazine, quinoxaline, acridine, pyrimidine, quinazoline, pyridazine, pyridazine, cinnoline phthalazin, 1,2,3-triazine, 1,2,4-triazine, and 1,3,5-triazine (s-triazine).
5. The compound of claim 4 , wherein the arene or heteroarene comprises a substituent.
6. The compound of claim 5 , wherein the substituent is selected from halo, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, thiol, alkylthio, oxo, thioxy, alkylthioalkyl, alkyl sulfonyl, alkylsulfonylalkyl, alkoxy, aryloxy, aralkoxy, aminocarbonyl, alkylaminocarbonyl, alkoxycarbonyl, haloalkyl, amino, trifluoromethyl, cyano, nitro, alkylamino, alkylaminoalkyl, aminoalkylamino, hydroxy, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, acyl, carboxylic acid, sulfonic acid, sulfonyl, and phosphonic acid.
7. The compound of claim 1 , wherein the compound is selected from the group consisting of lipids 13, 14, 15, 16, 17, 18, 19, and 20
8. The compound of claim 4 , wherein the arene or heteroarene consists of benzene, naphthalene, or anthracene.
9. The compound of claim 1 , wherein r=0.
10. The compound of claim 1 , wherein Z=S.
11. The compound of claim 1 , wherein L=C 2 or C 3 alkyl.
12. The compound of claim 1 , wherein L is further substituted with C 1 to C 3 alkyl.
13. The compound of claim 1 , wherein R 3 and R 4 are methyl.
14. The compound of claim 1 , wherein *-Z-L-NR 3 R 4 consists of a moiety selected from
15. The compound of claim 1 , wherein the compound consists of formula II or formula III
wherein
Y is a bond, an alkenylene, or a monocyclic, bicyclic, or tricyclic arene or heteroarene;
Z is S or O;
L is a linear or branched alkylene of 1 to 6 carbons;
R 3 and R 4 are independently a linear or branched alkyl of 1 to 6 carbons;
R 1 and R 2 are independently a linear or branched alkyl or alkenyl of 1 to 20 carbons;
r is 0 to 6; and
m, n, p, and q are independently 1 to 18;
or a pharmaceutically acceptable salt thereof.
16. The compound of claim 15 , wherein n and m each is 1 to 4.
17. The compound of claim 15 , wherein R 1 and R 2 are independently linear or branched alkyl or alkenyl of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbons.
18. The compound of claim 15 , wherein Y is a bond.
19. The compound of claim 15 , wherein r=0 and Z=S.
20. The compound of claim 1 , wherein one or both of R 1 and R 2 is a branched alkyl.