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 represented by a formula:
wherein D is optionally substituted C 3-6 carbocyclyl, optionally substituted C 2-5 heterocyclyl, isopropyl, or t-butyl;
Bz is optionally substituted benzoimidazol-1,2-diyl;
A is C 1-8 alkyl;
X is F; and
Y is H, F, Cl, Br, I, or a moiety having a molecular weight of 15 Da to 300 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or Br.
2. A compound represented by a formula:
wherein D is optionally substituted cyclobutyl, optionally substituted phenyl, optionally substituted isoxazolyl, optionally substituted pyridinyl, isopropyl, or t-butyl;
A is C 2-8 alkyl;
X is H, F, CF 3 optionally substituted phenyl, or optionally substituted pyridinyl;
Y is H, F, Cl, Br, I, or a moiety having a molecular weight of 15 Da to 300 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or Br;
R 1 is F, Cl, Br, CN, OCH 3 , CHF 2 , CF 3 , C 1-4 —CO 2 -alkyl, C 1-4 alkyl, —CH 2 CO 2 H, —CH 2 CO 2 CH 2 CH 3 or —CH 2 CON(CH 3 ) 2 , or C 1-5 hydroxyalkyl; and
R 2 , R 3 , and R 4 are independently H, F, Cl, Br, I, or a substituent having a molecular weight of 15 Da to 200 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or Br.
3. The compound of claim 2 , wherein Y is H, F, CF 3 , OH, C 1-5 O-alkyl, C 0-6 alkylamino, optionally substituted tetrahydropyranyl, or C 0-6 fluoroalkylamino.
4. The compound of claim 2 , wherein R 1 is Cl, Br, —OCH 3 , —CN, —CF 3 , —CH 2 OH, —COOCH 2 CH 3 , —C(CH 3 ) 2 OH, —CHOHCH 2 CH 3 , —CHOHCH 3 , —CHF 2 , —CH(CH 3 ) 2 , —C(CH 2 CH 3 ) 2 OH, —CH 2 COOCH 2 CH 3 , —CH 2 C(CH 3 ) 2 OH, —CH 2 COOH, or —CH 2 CON(CH 3 ) 2 .
5. The compound of claim 2 , wherein R 2 is H, F, —CH 2 OH, —CO 2 Me, or —C(CH 3 ) 2 OH.
6. The compound of claim 2 , wherein R 3 is H.
7. The compound of claim 2 , wherein R 4 is H, —CH 3 , or —CF 3 .
8. The compound of claim 1 , wherein D is optionally substituted cyclobutyl, optionally substituted phenyl, optionally substituted isoxazolyl, optionally substituted pyridinyl, isopropyl, or t-butyl.
9. The compound of claim 8 , wherein each substituent of D and Y, if present, independently has a molecular weight of 15 Da to 200 Da and consists of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or Br.
10. The compound of claim 2 , wherein R 1 is Cl, Br, CN, OCH 3 , CF 3 , —CO 2 CH 2 CH 3 , C 1-4 alkyl, or C 1-4 hydroxyalkyl.
11. The compound of claim 2 , wherein X is optionally substituted phenyl.
12. The compound of claim 2 , wherein X is CF 3 .
13. The compound of claim 2 , wherein X is optionally substituted pyridinyl.
14. The compound of claim 2 , wherein X is H.
15. The compound of claim 2 , wherein Y is H.
16. The compound of claim 2 , wherein Y is OH.
17. A compound represented by a formula:
18. A method of mitigating disorder associated with a Kv7 potassium channel activator comprising administering an effective amount of a compound of claim 17 to a mammal in need thereof, wherein the disorder is epilepsy, pain or migraine.
19. The method of claim 18 , wherein the disorder is epilepsy, neuropathic pain, inflammatory pain, persistent pain, cancer pain, postoperative pain, or migraine.