Chemical Compounds
Provided are compounds and pharmaceutical compositions and uses thereof for inhibiting Na v 1.8 voltage-gated sodium ion channels and treating Na v 1.8 mediated diseases, such as pain and pain-associated diseases, and cardiovascular diseases.
1 . A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
2 . The compound of claim 1 , being a pharmaceutically acceptable salt of the compound selected from the group consisting of:
wherein:
R 1 is —P(O)(OH)O − M + , —PO(O − ) 2 ·2M + , or —PO(O − ) 2 ·D 2+ ;
each M + is independently a pharmaceutically acceptable monovalent cation; and
D 2+ is a pharmaceutically acceptable divalent cation.
3 . The compound of claim 1 , which is:
or a pharmaceutically acceptable salt thereof.
4 . The compound of claim 1 , which is:
or a pharmaceutically acceptable salt thereof.
5 . The compound of claim 1 , which is:
or a pharmaceutically acceptable salt thereof.
6 . The compound of claim 1 , which is:
or a pharmaceutically acceptable salt thereof.
7 . The compound of claim 1 , which is:
or a pharmaceutically acceptable salt thereof.
8 . A compound selected from the group consisting of:
or a tautomer thereof, or a pharmaceutically acceptable salt thereof.
9 . A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt thereof according to claim 1 , and a pharmaceutically acceptable excipient.
10 . A pharmaceutical composition comprising the compound, or tautomer thereof, or pharmaceutically acceptable salt thereof according to claim 8 , and a pharmaceutically acceptable excipient.
11 . The pharmaceutical composition according to claim 9 , formulated for oral administration.
12 . The pharmaceutical composition according to claim 9 , formulated for intravenous administration.
13 . A method of treatment of pain or a pain-associated disease in a human in need thereof, the method comprising administering to the human a compound according to claim 1 , or a tautomer thereof, or a pharmaceutically acceptable salt thereof.
14 . A method of treatment of atrial fibrillation in a human in need thereof, the method comprising administering to the human a compound according to claim 1 , or a tautomer thereof, or a pharmaceutically acceptable salt thereof.
15 .- 19 . (canceled)
20 . The method according to claim 13 , wherein the pain or pain-associated disease is neuropathic pain, ambulatory post-operative pain, or osteoarthritis.
21 . A method of treatment of pain or a pain-associated disease in a human in need thereof, the method comprising administering to the human a compound according to claim 8 , or a tautomer thereof, or a pharmaceutically acceptable salt thereof.
22 . A method of treatment of atrial fibrillation in a human in need thereof, the method comprising administering to the human a compound according to claim 8 , or a tautomer thereof, or a pharmaceutically acceptable salt thereof.
23 . The method according to claim 21 , wherein the pain or pain-associated disease is neuropathic pain, ambulatory post-operative pain, or osteoarthritis.
24 . A method of treatment of pain or a pain-associated disease in a human in need thereof, the method comprising administering to the human a pharmaceutical composition according to claim 9 .
25 . A method of treatment of atrial fibrillation in a human in need thereof, the method comprising administering to the human a pharmaceutical composition according to claim 9 .