Pharmacological correctors of rhodopsin and uses thereof
Described herein are pharmacologic correctors of rhodopsin, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in treating disease.
1 . A compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof:
wherein:
each R 1 is independently selected from halogen, —CN, —OH, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy;
R 2 is C 1-6 alkyl or C 1-6 haloalkyl;
R 3 is hydrogen, —CN, or C 1-6 alkoxy, wherein if R 3 is hydrogen, then R 2 is C 1-6 haloalkyl;
each R 4 is independently selected from halogen, —CN, C 1-6 alkyl, and C 1-6 haloalkyl;
n is 2, 3, or 4; and
p is 0, 1, 2, or 3.
2 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is C 1-6 haloalkyl.
3 . The compound of claim 2 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is —CF 2 H.
4 . The compound of compound 1, or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is C 1-6 alkyl.
5 . The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is —CH 3 .
6 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 3 is hydrogen.
7 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 3 is C 1-6 alkoxy.
8 . The compound of claim 7 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 3 is —OCH 3 .
9 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 3 is —CN.
10 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0.
11 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein each R 1 is independently selected from halogen, C 1-6 alkyl, and C 1-6 alkoxy.
12 . The compound of claim 11 , or a pharmaceutically acceptable salt or solvate thereof, wherein each R 1 is independently selected from halogen and C 1-6 alkyl.
13 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2.
14 . The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein n is 3.
15 . A compound, or a pharmaceutically acceptable salt or solvate thereof, selected from:
16 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, that is:
17 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, that is:
18 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, that is:
19 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, that is:
20 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, that is:
21 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, that is:
22 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, that is:
23 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, that is:
24 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, that is:
25 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, that is:
26 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, that is:
27 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.
28 . A method of treating autosomal dominant retinitis pigmentosa (adRP) in a subject in need thereof, comprising administering to the subject a compound of claim 1 , or a pharmaceutically acceptable salt or solvate.