Imidazo(4,5-
Compounds represented by formula 1 can be potent and/or partially selective for the Kv7.2/7.3 heteromultimer. They may be useful in treating disorders related to seizures, pain, neurotransmitter release, etc.
1. A compound represented by a formula:
wherein L is CH 2 , CF 2 , CHCH 3 , CH 2 CH 2 , C 3 H 6 , CH 2 O, C 2 H 4 O, or C 3 H 6 O with the O of CH 2 O, C 2 H 4 O, or C 3 H 6 O bonded with R 1 ;
wherein R 1 is optionally substituted C 1-2 alkyl, optionally substituted C 5-10 cycloalkyl, optionally substituted C 1-12 —O-alkyl, optionally substituted C 6-10 aryl, optionally substituted C 6-10 —O-aryl, or optionally substituted C 2-9 heterocyclyl, wherein the optional substituents of R 1 are independently R A , F, Cl, CN, OR A , CF 3 , NR A R B , COR A , CO 2 R A , OCOR A , NR A COR B , CONR A R B , wherein R A and R B are independently H or C 1-12 alkyl;
wherein R 2 is optionally substituted C 2-4 acyclic alkyl, optionally substituted cyclobutyl, optionally substituted C 6-10 aryl, or optionally substituted C 2-9 heterocyclyl, wherein the optional substituents of R 2 are independently F, Cl, Br, I, CN, C 1-6 alkyl, C 1-6 —O-alkyl, C 1-6 alkylamine, C 1-6 aminoalkyl, C 1-6 aminoacyl, C 1-6 alkylthio, or C 1-6 alkylsulfonyl;
wherein R 3 , R 4 , and R 5 are independently H, F, Cl, Br, I, CN, optionally substituted C 1-12 alkyl, optionally substituted C 1-12 —O-alkyl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 6-10 aryl, optionally substituted C 2-9 —O-heterocyclyl, optionally substituted C 6-10 O-aryl, optionally substituted C 1-12 acylamino, optionally substituted C 1-12 aminoacyl, or optionally substituted C 1-12 aminoalkyl, wherein the optional substituents of R 3 , R 4 , or R 5 are independently F, Cl, Br, I, CN, C 1-6 alkyl, C 1-6 —O-alkyl, C 1-6 alkylamine, C 1-6 aminoalkyl, C 1-6 aminoacyl, C 1-6 acylamino, C 1-6 alkylthio, or C 1-6 alkylsulfonyl.
2. The compound of claim 1 , wherein R 2 is optionally substituted C 4 H 9 , optionally substituted cyclobutyl, optionally substituted C 6-10 aryl, or optionally substituted C 2-9 heterocyclyl.
3. The compound of claim 2 , wherein R 2 is optionally substituted C 4 H 9 , or optionally substituted cyclobutyl.
4. The compound of claim 2 , wherein R 2 is optionally substituted phenyl, or optionally substituted C 2-9 heterocyclyl.
5. The compound of claim 1 , wherein R 1 is optionally substituted phenyl.
6. The compound of claim 1 , wherein R 1 is optionally substituted C 1-2 alkyl.
7. The compound of claim 1 , wherein R 1 is optionally substituted cyclopentyl or optionally substituted cyclohexyl.
8. The compound of claim 1 , wherein R 1 is C 2-4 —O-alkyl.
9. The compound of claim 1 , wherein R 1 is optionally substituted tetrahydrofuranyl or optionally substituted tetrahydro-2H-pyranyl.
10. The compound of claim 1 , wherein R 1 is
11. The compound of claim 1 , wherein R 2 is
12. The compound of claim 1 , wherein R 3 is CF 3 , Cl, CN, OCH 3 , or H.
13. The compound of claim 12 , wherein R 1 is
14. The compound of claim 1 , wherein R 4 is CH 3 , CF 3 , Cl, or H.
15. The compound of claim 14 , wherein R 2 is
16. A compound represented by a formula:
17. A pharmaceutical dosage form comprising a compound of claim 1 .
18. A method of treating a disorder associated with a Kv7 potassium channel activator comprising administering an effective amount of a compound of claim 1 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.
20. A method of treating a disorder associated with a Kv7 potassium channel activator comprising administering an effective amount of a compound of claim 16 to a mammal in need thereof, wherein the disorder is epilepsy, pain or migraine.
21. The method of claim 20 , wherein the disorder is epilepsy, neuropathic pain, inflammatory pain, persistent pain, cancer pain, postoperative pain or migraine.
22. A method of activating a Kv7 potassium channel comprising administering an effective amount of a compound of claim 1 to a mammal in need thereof.
23. A method of activating a Kv7 potassium channel comprising administering an effective amount of a compound of claim 16 to a mammal in need thereof.