Derivatives of rufinamide and their use in inhibtion of the activation of human voltage-gated sodium channels
The present invention provides compounds of formula I which are capable of inhibition of the activation of hNav1.1 or hNav1.6 sodium channels in neurons. Pharmaceutical compositions comprising these compounds are also provided. Methods for prevention and treatment of neurological disorders, including, for example, seizures and seizure disorders, including Lennox-Gastaut Syndrome, Dravet syndrome, epileptic encephalopathies, autism, Familial hemiplegic migraine (FHM), anxiety disorders, including Post-traumatic stress disorder (PTSD), panic disorder and obsessive-compulsive disorder, neuropathic pain, and Rett syndrome by administration of these compounds are also provided.
1. A method for inhibition of the activation of one or more voltage-gated sodium hNav1.1 or hNav1.6 channels in one or more neurons of a subject comprising administering to the subject an effective amount of a compound selected from the group consisting of:
or a salt, solvate, or stereoisomer thereof.
2. The method of claim 1 , wherein the one or more voltage-gated sodium (Nav) channels are hNav1.1 channels.
3. The method of claim 1 , wherein the one or more voltage-gated sodium (Nav) channels are hNav1.6 channels.
4. A method for treating a seizure disorder in a subject comprising administering to the subject an effective amount of a compound selected from the group consisting of:
or a salt, solvate, or stereoisomer thereof.
5. The method of claim 4 , wherein the seizure disorder is epilepsy.
6. The method of claim 4 , wherein the epilepsy disorder is Lennox-Gastaut Syndrome (LGS).
7. A method for treating an anxiety disorder in a subject comprising administering to the subject an effective amount of a compound selected from the group consisting of:
or a salt, solvate, or stereoisomer thereof.
8. The method of claim 7 , wherein the anxiety disorder is post-traumatic stress disorder.
9. A method for treating migraine in a subject comprising administering to the subject an effective amount of a compound selected from the group consisting of:
or a salt, solvate, or stereoisomer thereof.
10. A method for treating neuropathic pain in a subject comprising administering to the subject an effective amount of a compound selected from the group consisting of:
or a salt, solvate, or stereoisomer thereof.
11. The method of claim 10 , wherein the neuropathic pain is caused by Diabetes.
12. A method for inhibition of the activation of one or more voltage-gated sodium hNav1.1 or hNav1.6 channels in one or more neurons of a subject comprising administering to the subject an effective amount of a pharmaceutical composition selected from the group consisting of:
or a salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable carrier.
13. The method of claim 12 , wherein the one or more voltage-gated sodium (Nay) channels are hNav1.1 channels.
14. The method of claim 12 , wherein the one or more voltage-gated sodium (Nay) channels are hNav1.6 channels.
15. A method for treating a seizure disorder in a subject comprising administering to the subject an effective amount of a pharmaceutical composition selected from the group consisting of:
or a salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable carrier.
16. The method of claim 15 , wherein the seizure disorder is epilepsy.
17. The method of claim 15 , wherein the epilepsy disorder is Lennox-Gastaut Syndrome (LGS).
18. A method for treating an anxiety disorder in a subject comprising administering to the subject an effective amount of a pharmaceutical composition selected from the group consisting of:
or a salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable carrier.
19. The method of claim 18 , wherein the anxiety disorder is post-traumatic stress disorder.
20. A method for treating migraine in a subject comprising administering to the subject an effective amount of a pharmaceutical composition selected from the group consisting of:
or a salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable carrier.
21. A method for treating neuropathic pain in a subject comprising administering to the subject an effective amount of a pharmaceutical composition selected from the group consisting of:
or a salt, solvate, or stereoisomer thereof, and a pharmaceutically acceptable carrier.
22. The method of claim 21 , wherein the neuropathic pain is caused by Diabetes.