Benzoimidazol-1,2-yl amides as Kv7 channel activators
Optionally substituted benzoimidazol-1,2-yl amides, such as compounds of Formula 1 or Formula 2, can be used to treat disorders associated with a Kv7 potassium channel activator. Compositions, medicaments, and dosage forms related to the treatment are also disclosed herein.
1. A compound of Formula 2:
or a pharmaceutically acceptable salt thereof;
wherein
D is optionally substituted cyclobutyl, or t-butyl;
A is C 2-8 alkyl;
X is H, CF 3 , or optionally substituted phenyl;
Y is H or OH;
R 1 is CN or C 1-4 hydroxyalkyl; and
R 2 , R 3 , and R 4 are independently H, or F.
2. The compound of claim 1 , wherein R 1 is CN, —C(CH 3 ) 2 OH, or —CH 2 C(CH 3 ) 2 OH.
3. The compound of claim 1 , wherein R 2 is F.
4. The compound of claim 1 , wherein R 3 is H.
5. The compound of claim 1 , wherein R 4 is H.
6. The compound of claim 1 , wherein R 1 is CN.
7. The compound of claim 1 , wherein R 1 is C 1-4 hydroxyalkyl.
8. The compound of claim 1 , wherein X is optionally substituted phenyl.
9. The compound of claim 1 , wherein X is CF 3 .
10. The compound of claim 1 , wherein X is H.
11. The compound of claim 1 , wherein Y is H.
12. The compound of claim 1 , wherein Y is OH.
13. A method of mitigating epilepsy in a mammal in need thereof, comprising administering an effective amount of the compound of claim 1 to the mammal.
14. A method of mitigating pain in a mammal in need thereof, comprising administering an effective amount of the compound of claim 1 to the mammal.
15. The method of claim 14 , wherein the pain is neuropathic pain, inflammatory pain, persistent pain, cancer pain, or postoperative pain.
16. A method of mitigating migraine in a mammal in need thereof, comprising administering an effective amount of the compound of claim 1 to the mammal.