KV7 channel activators compositions and methods of use
Provided herein are optionally substituted benzoimidazol-1,2-yl amides, pharmaceutical compositions comprising a therapeutically effective amount of such compounds and a pharmaceutically acceptable excipient, and methods of treating Kv7 associated diseases, such as, epilepsy, amyotrophic lateral sclerosis, various types of pain, hyperexcitability, a dyskinesia, dystonia, mania and tinnitus with such compounds and pharmaceutical compositions.
1. A compound represented by a formula:
wherein
D is optionally substituted cyclobutyl, optionally substituted phenyl, or optionally substituted C 2-5 alkyl, wherein the optional substituents are selected from —CH 3 and F;
A is C 1 alkyl;
X is substituted cyclobutyl, wherein the substituent is F;
Y is H;
R 1 is selected from H, C 3 hydroxyalkyl, CN, F, or Cl;
R 2 is selected from H, CN, F, Br, or —OCF 3 ;
R 3 is selected from H, F, or —OCH 3 ;
R 4 is H or F; and
wherein when X is substituted with 2 fluorine atoms, the fluorine atoms are not geminal;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
5. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition comprising a compound of claim 2 , or a pharmaceutically acceptable salt thereof.
7. A pharmaceutical composition comprising a compound of claim 3 , or a pharmaceutically acceptable salt thereof.
8. A pharmaceutical composition comprising a compound of claim 4 , or a pharmaceutically acceptable salt thereof.
9. The compound of claim 2 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
10. The compound of claim 2 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
11. The compound of claim 2 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 3 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 3 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
14. The compound of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
15. The compound of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
16. The compound of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
17. The compound of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
18. The compound of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
19. The compound of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
20. The compound of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.