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 method of treating a Kv7 associated disorder selected from the group consisting of epilepsy, pain, neuropathic pain, inflammatory pain, persistent pain, cancer pain, postoperative pain, tinnitus, epileptic encephalopathy, treatment-resistant epilepsy, congenital neurological disorder with intellectual disability or epileptic encephalopathy, severe epileptic encephalopathies, congenital neurodevelopmental disorder with phenotypes of nonsyndromic intellectual disability or epileptic encephalopathy, epileptic spasms, epileptic encephalopathy, early infantile epileptic encephalopathy 7, early infantile epileptic encephalopathy with delayed psychomotor development, and combinations thereof, in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound represented by Formula 8c:
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;
wherein when X is substituted with 2 fluorine atoms, the fluorine atoms are not geminal;
or a pharmaceutically acceptable salt thereof; and
wherein the subject is treated.
2. The method of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
5. The method of claim 2 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
6. The method of claim 2 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
7. The method of claim 2 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
8. The method of claim 3 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
9. The method of claim 3 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
10. The method of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
11. The method of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
12. The method of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
13. The method of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
14. The method of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
15. The method of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
16. The method of claim 4 , wherein the compound is
or a pharmaceutically acceptable salt thereof.