Methods for treating malaria using potassium channel inhibitors
View Patent ↗The present invention relates to the field of anti-malarials. In particular, the disclosure relates to methods for treating malaria in a subject by administering to said subject a potassium channel inhibitor. The disclosed potassium channel inhibitors provide wide bioavailability, long half-life, and good toxicity profiles while showing high potency for killing parasites which cause malaria. In certain exemplary embodiments, the potassium channel inhibitor is an inhibitor of calcium-activated potassium channels. In certain exemplary embodiments, the potassium channel inhibitor is an inhibitor of the Gardos channel.
1. A method for treating malaria, comprising administering to a subject in need thereof a therapeutically effective amount of a potassium channel inhibitor, wherein the potassium channel inhibitor is a compound of Formula (I):
wherein:
m, n and p are independently 0 or 1, provided that at least one of m, n and p is 1;
R 1 and R 2 are independently H or alkyl;
R 3 , R 4 and R 5 are independently halogen, alkyl, alkenyl, alkynyl or alkoxy; and
any stereoisomer, solvate or pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein at least two of m, n and p are 1.
3. The method of claim 2 , wherein all three of m, n and p are 1.
4. The method of claim 1 , wherein R 1 and R 2 are independently H or C 1 -C 6 alkyl.
5. The method of claim 4 , wherein R 1 and R 2 are independently H, methyl, ethyl or propyl.
6. The method of claim 5 , wherein R 1 and R 2 are H.
7. The method of claim 1 , wherein at least one of R 3 , R 4 and R 5 is a halogen.
8. The method of claim 1 , wherein at least one of R 3 , R 4 and R 5 is an alkyl.
9. The method of claim 1 , wherein at least one of R 3 , R 4 and R 5 is an alkoxy.
10. The method of claim 1 , wherein R 3 , R 4 and R 5 are independently halogen, C 1 -C 6 alkyl or C 1 -C 6 alkoxy.
11. The method of claim 10 , wherein R 3 , R 4 and R 5 are independently F, Cl, methyl or methoxy.
12. The method of claim 1 , wherein the compound is of Formula (II):
wherein:
m, n and p are independently 0 or 1, provided that at least one of m, n and p is 1; and
any stereoisomer, solvate or pharmaceutically acceptable salt thereof.
13. The method of claim 12 , wherein the compound is of Formula (III):
wherein:
m, n and p are independently 0 or 1, provided that at least one of m, n and p is 1; and
any stereoisomer, solvate or pharmaceutically acceptable salt thereof.
14. The method of claim 1 , wherein the compound is of Formula (IV):
wherein:
m is either 0 or 1; and
any stereoisomer, solvate or pharmaceutically acceptable salt thereof.
15. The method of claim 1 , wherein the potassium channel inhibitor is selected from the group consisting of:
and
any stereoisomer, solvate or pharmaceutically acceptable salt thereof.
16. The method of claim 1 , wherein the potassium channel inhibitor is senicapoc (2,2-bis(4-fluorophenyl)-2-phenylacetamide).
17. A method for treating malaria, comprising administering to a subject in need thereof a therapeutically effective amount of a potassium channel inhibitor, wherein the potassium channel inhibitor is