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 cyclobutyl;
A is C 1-8 alkyl;
X is CF 3 ;
Y is H;
R 1 is H, Cl, Br, CN, OCH 3 , CF 3 , —CO 2 CH 2 CH 3 , C 1-4 alkyl, or C 1-4 hydroxyalkyl;
R 2 is H, F, —CH 2 OH, —CO 2 Me, or —C(CH 3 ) 2 OH;
R 3 is 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; and
R 4 is H, —CH 3 , or —CF 3 .
2. A composition comprising a compound of claim 1 , wherein the composition is pharmaceutically acceptable and further comprises a pharmaceutically acceptable excipient.
3. A method of treating a disease selected from epilepsy, pain, migraine, and tinnitus comprising administering an effective amount of a compound of claim 1 to a mammal in need thereof.
4. The method of claim 3 , wherein the pain is selected from neuropathic pain, inflammatory pain, persistent pain, cancer pain and postoperative pain.
5. A compound represented by a formula:
wherein:
D is optionally substituted cyclobutyl;
A is C 1-8 alkyl;
X is CF 3 ;
Y is H;
R 1 is H, Cl, Br, CN, OCH 3 , CF 3 , —CO 2 CH 2 CH 3 , C 1-4 alkyl, or C 1-4 hydroxyalkyl;
R 2 is H, F, —CH 2 OH, —CO 2 Me, or —C(CH 3 ) 2 OH;
R 3 is H; and
R 4 is H, —CH 3 , or —CF 3 .
6. A composition comprising a compound of claim 5 , wherein the composition is pharmaceutically acceptable and further comprises a pharmaceutically acceptable excipient.
7. A method of treating a disease selected from epilepsy, pain, migraine, and tinnitus comprising administering an effective amount of a compound of claim 5 to a mammal in need thereof.
8. The method of claim 7 , wherein the pain is selected from neuropathic pain, inflammatory pain, persistent pain, cancer pain and postoperative pain.
9. A compound represented by a formula:
wherein:
D is t-butyl;
A is C 1-8 alkyl;
X is H;
Y is H;
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;
R 2 is H, F, —CH 2 OH, —CO 2 Me, or —C(CH 3 ) 2 OH;
R 3 is 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; and
R 4 is H, —CH 3 , or —CF 3 .
10. A composition comprising a compound of claim 9 , wherein the composition is pharmaceutically acceptable and further comprises a pharmaceutically acceptable excipient.
11. A method of treating a disease selected from epilepsy, pain, migraine, and tinnitus comprising administering an effective amount of a compound of claim 9 to a mammal in need thereof.
12. The method of claim 11 , wherein the pain is selected from neuropathic pain, inflammatory pain, persistent pain, cancer pain and postoperative pain.
13. A compound represented by a formula:
wherein:
D is t-butyl;
A is C 1-8 alkyl;
X is CF 3 ;
Y is H;
R 1 is H, Cl, Br, CN, OCH 3 , CF 3 , —CO 2 CH 2 CH 3 , C 1-4 alkyl, or C 1-4 hydroxyalkyl;
R 2 is H, F, —CH 2 OH, —CO 2 Me, or —C(CH 3 ) 2 OH;
R 3 is 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; and
R 4 is H, —CH 3 , or —CF 3 .
14. A composition comprising a compound of claim 13 , wherein the composition is pharmaceutically acceptable and further comprises a pharmaceutically acceptable excipient.
15. A method of treating a disease selected from epilepsy, pain, migraine, and tinnitus comprising administering an effective amount of a compound of claim 13 to a mammal in need thereof.
16. The method of claim 15 , wherein the pain is selected from neuropathic pain, inflammatory pain, persistent pain, cancer pain and postoperative pain.