Oxysterols and methods of use thereof
Compounds are provided according to Formula (I), and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein A, R 1 , and R 5 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
1. A compound of Formula (I-B):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is hydrogen or substituted or unsubstituted C 1-6 alkyl;
R 5 is absent or hydrogen;
Z is —C(R A ) 2 —, —NR B —, —O—, or —S—;
X is halogen, substituted or unsubstituted C 1-6 alkyl, or —OR C ;
R A is hydrogen, halogen, or substituted or unsubstituted C 1-6 alkyl;
R B is hydrogen, substituted or unsubstituted C 1-6 alkyl, —C(O)R C , —C(O)OR C , —C(O)N(R D ) 2 , or —S(O) 2 R C ;
R C is hydrogen or substituted or unsubstituted C 1-6 alkyl;
each R D is independently hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
m is an integer selected from 1, 2, and 3;
n is an integer selected from 1, 2, and 3;
p is an integer selected from 0, 1, 2, 3, 4, and 5; and
represents a single or double bond, wherein when one is a double bond, then the other is a single bond and R 5 is absent.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of Formula (II-A), Formula (II-B), or Formula (II-C):
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein p is an integer selected from 0, 1, or 2.
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein p is 0.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein p is 1.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein p is 1 and X is halogen.
7. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (II-D), Formula (II-E), or Formula (II-F):
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is substituted or unsubstituted C 1-6 alkyl.
9. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein R 1 is methyl or ethyl.
10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (II-G) or Formula (II-H):
11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is of Formula (II-I) or Formula (II-J):
12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is —C(R A ) 2 —, —O—, or —NR B —.
13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R A is halogen.
14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is —CH 2 —, —CF 2 —, or —C(CH 3 ) 2 —.
15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is —O— or —NR B —.
16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is —NH—, —NCH 3 —, or —NC(O)CH 3 —.
17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is —CH 2 —.
18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is —C(CH 3 ) 2 —.
19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is —CF 2 —.
20. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 1, n is 2, and Z is —O—.
21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 2 and n is 2.
22. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 3 and n is 1.
23. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 3, n is 1, and Z is —O—.
24. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 2, n is 2, and Z is —O— or —NR B —.
25. A compound selected from:
26. A pharmaceutically acceptable salt of a compound selected from:
27. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.