Method of treating of demyelinating diseases or conditions
View Patent ↗N-(Pyridinyl)-1H-indol-1-amines of formula I provide a unique combination of blocking properties for both the potassium and sodium channels. These compounds are useful for the treatment of Demyelinating Diseases and Conditions such as Multiple Sclerosis, Spinal Cord Injury, Traumatic Brain Injury and Stroke. The compounds are also useful for Stroke Rehabilitation, the treatment of Bladder Irritation and Dysfunction, and the treatment of Neuropathic Pain and Chemokine-Induced Pain.
1. A method of treating the loss of mobility that results from an injury to the spinal cord comprising administering to a patient in need thereof a therapeutically effective amount of the compound of Formula I
wherein
m is 0, 1 or 2;
n is 0, 1 or 2;
p is 0 or 1;
each R is independently hydrogen, halogen, trifluoromethyl, C 1 -C 8 alkyl, C 1 -C 6 alkoxy, benzyloxy, hydroxy, nitro or amino;
each R 1 is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 8 alkenyl,
C 1 -C 6 alkanoyl, halogen, cyano, —C(O)C 1 -C 6 alkyl, —C 1 -C 6 alkyleneCN, —C 1 -C 6 alkyleneNR′R″ wherein R′ and R″ are each independently hydrogen or C 1 -C 8 alkyl, —C 1 -C 6 alkyleneOC(O)C 1 -C 6 alkyl, or —CH(OH)R 4 wherein R 4 is hydrogen or C 1 -C 8 alkyl;
R 2 is hydrogen, C 1 -C 6 alky optionally substituted with halogen, hydroxy or benzyloxy, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl,
—CO 2 C 1 -C 6 alkyl, or —R 5 —NR′R″ wherein R 5 is C 1 -C 6 alkylene, C 1 -C 6 alkenylene or C 1 -C 6 alkynylene and R′ and R″ are each independently hydrogen, C 1 -C 6 alkyl or alternatively the group —NR′R″ as a whole is 1 pyrrolidinyl; and
R 3 is hydrogen, nitro, amino, halogen, C 1 -C 6 alkoxy, hydroxy or C 1 -C 6 alkyl
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 wherein R is hydrogen, halogen, trifluoromethyl, or C 1 -C 6 alkyl; R 1 is hydrogen or C 1 -C 6 alkyl; R 2 is hydrogen or C 1 -C 6 alkyl; R 3 is hydrogen, C 1 -C 6 alkyl or halogen; and p is 0.
3. The method of claim 2 wherein the compound is
4. The method of claim 2 wherein the compound is
5. A method of improving motor function in patients with Spinal Cord injury comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 .
6. The method of claim 5 wherein R is hydrogen, halogen, trifluoromethyl, or C 1 -C 6 alkyl; R 1 is hydrogen or C 1 -C 6 alkyl; R 2 is hydrogen or C 1 -C 6 alkyl; R 3 is hydrogen, C 1 -C 6 alkyl or halogen; and p is 0.
7. The method of claim 6 wherein the compound is
8. The method of claim 6 wherein the compound is
9. A method of improving motor function in patients with Spinal Cord Injury wherein the Spinal Cord Injury is acute comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 .
10. The method of claim 9 wherein R is hydrogen, halogen, trifluoromethyl or C 1 -C 6 alkyl; R 1 is hydrogen or C 1 -C 6 alkyl; R 2 is hydrogen or C 1 -C 6 alkyl; R 3 is hydrogen, C 1 -C 6 alkyl or halogen; and p is 0.
11. The method of claim 10 wherein the compound is
12. The method of claim 10 wherein the compound is
13. A method of improving motor function in patients with Spinal Cord Injury wherein the Spinal Cord Injury is long-standing comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 .
14. The method of claim 13 wherein R is hydrogen, halogen, trifluoromethyl, or C 1 -C 6 alkyl; R 1 is hydrogen or C 1 -C 6 alky; R 2 is hydrogen or C 1 -C 6 alkyl; R 3 is hydrogen, C 1 -C 6 alkyl or halogen; and p is 0.
15. The method of claim 14 wherein the compound is
16. The method of claim 14 wherein the compound is
17. A method of treating the loss of feeling that results from an injury to the spinal cord comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 .
18. The method of claim 17 wherein R is hydrogen, halogen, trifluoromethyl, or C 1 -C 6 alkyl; R 1 is hydrogen or C 1 -C 6 alkyl; R 2 is hydrogen or C 1 -C 6 alkyl; R 3 is hydrogen, C 1 -C 6 alkyl or halogen; and p is 0.
19. The method of claim 18 wherein the compound is
20. The method of claim 18 wherein the compound is
21. A method of enhancing muscle function in patients with Spinal Cord Injury comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 .
22. The method of claim 21 wherein R is hydrogen, halogen, trifluoromethyl, or C 1 -C 6 alkyl; R 1 is hydrogen or C 1 -C 6 alkyl; R 2 is hydrogen or C 1 -C 6 alkyl; R 3 is hydrogen, C 1 -C 6 alkyl or halogen; and p is 0.
23. The method of claim 22 wherein the compound is
24. The method of claim 22 wherein the compound is