Sodium channel modulators
View Patent ↗The invention provides sodium channel modulating compounds which are useful for treating diseases or conditions associated with sodium channel activity, such as neuropathic pain. The invention also provides pharmaceutical compositions comprising a compound of the present invention, as well as therapeutic methods comprising administering such a compound or salt to a mammal (e.g. a human).
1. A compound of formula (III):
wherein:
A 6 and A 7 are each independently alkylene or substituted alkylene;
each R 20 is independently halo, alkyl, substituted alkyl, aryl, alkoxy, substituted alkoxy, cycloalkoxy, substituted cycloalkoxy, trifluoromethyl, cyano, nitro, hydroxy, NR 4 R 5 , or CO 2 R 6 ;
R 21 is hydrogen, alkyl, or substituted alkyl;
each R 22 is independently halo, alkyl, substituted alkyl, aryl, heteroaryl, cycloalkyl, substituted cycloalkyl, heterocycle, alkoxy, substituted alkoxy, cycloalkoxy, substituted cycloalkoxy, trifluoromethyl, cyano, nitro, hydroxy, NR 4 R 5 , or CO 2 R 6 ;
y is 0, 1, 2, 3, 4, or 5;
z is 0, 1, 2, 3, 4, or 5; and
R 4 –R 6 are each independently hydrogen, alkyl, or substituted alkyl;
wherein any aryl of A 6 , A 7 , R 20 –R 22 and R 4 –R 6 can optionally be substituted with from 1 to 5 substituents R g ; wherein each R g is independently selected from the group consisting of hydroxy, alkyl, substituted alkyl, alkoxy, cycloalkoxy, substituted cycloalkoxy, methanediol, ethanediol, cycloalkyl, substituted alkoxy, substituted cycloalkyl, amino, substituted amino, aryl, aryloxy, carboxy, carboxylalkyl, carboxyl(substituted alkyl), cyano, halo, nitro, heteroaryl, heteroaryloxy, heterocyclic, heterocyclooxy, heteroaryl and trihalomethyl;
and wherein any heteroaryl of A 6 , A 7 , R 20 –R 22 and R 4 –R 6 can be optionally substituted with 1 to 5 substituents R h , wherein each R h is independently selected from the group consisting of hydroxy, alkyl, alkoxy, substituted alkoxy, cycloalkoxy, substituted cycloalkoxy, substituted alkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, substituted cycloalkyl, amino, substituted amino, aryl, aryloxy, carboxyl, carboxylalkyl, carboxyl(substituted alkyl), cyano, halo, nitro, heterocyclic, and trihalomethyl;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 wherein A 6 is methylene or 1,1-ethanediyl and A 7 is methylene.
3. The compound of claim 1 wherein R 21 is hydrogen or methyl.
4. The compound of claim 1 , which is selected from compounds 10–14, 16–20, 22–24 and 28–29:
or a pharmaceutically acceptable salt thereof.
5. A pharmaceutical composition comprising a compound as described in claim 1 ; and a pharmaceutically acceptable carrier.
6. A method of treating a disease or condition associated with sodium channel activity in a mammal, comprising administering to the mammal, a therapeutically effective amount of a compound as described in claim 1 .
7. The method of claim 6 wherein the disease or condition is neuropathic pain.
8. A method of treating a disease or condition associated with sodium channel activity in a mammal, comprising administering to the mammal, a therapeutically effective amount of a pharmaceutical composition of claim 5 .
9. The method of claim 8 wherein the disease or condition is neuropathic pain.
10. A compound of claim 1 wherein each R 20 is independently halo, alkyl, substituted alkyl, alkoxy, substituted alkoxy, trifluoromethyl, cyano or NR 4 R 5 .
11. A compound of claim 1 wherein each R 22 is independently halo, alkyl, substituted alkyl, alkoxy, substituted alkoxy, trifluoromethyl, cyano or NR 4 R 5 .