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 H;
Y is methyl(2,2,2-trifluoroethyl)amino;
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 .
2. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.
3. A method of mitigating a disorder associated with a Kv7 potassium channel comprising administering an effective amount of the pharmaceutical composition of claim 2 to a mammal in need thereof.
4. The method of claim 3 , wherein the disorder associated with a Kv7 potassium channel is selected from the group consisting of epilepsy, pain, tinnitus, migraine, a disorder of neurotransmitter release, a smooth muscle contractility disorder, a dyskinesia, dystonia, mania, a hearing disorder, anxiety, substance abuse, schizophrenia, a bladder disorder, a vasculature disorder, neuropathic pain, inflammatory pain, persistent pain, cancer pain, and postoperative pain.
5. A compound represented by a formula:
wherein:
D is cyclobutyl;
A is C 1-8 alkyl;
Xis CF 3 ;
Y is dimethylamino;
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 pharmaceutical composition comprising a compound of claim 5 and a pharmaceutically acceptable excipient.
7. A method of mitigating a disorder associated with a Kv7 potassium channel comprising administering an effective amount of the pharmaceutical composition of claim 6 to a mammal in need thereof.
8. The method of claim 7 , wherein the disorder associated with Kv7 potassium channel is selected from the group consisting of epilepsy, pain, tinnitus, migraine, a disorder of neurotransmitter release, a smooth muscle contractility disorder, a dyskinesia, dystonia, mania, a hearing disorder, anxiety, substance abuse, schizophrenia, a bladder disorder, a vasculature disorder, neuropathic pain, inflammatory pain, persistent pain, cancer pain, and postoperative pain.