Inhibitors of the plasmodial surface anion channel as antimalarials
Disclosed are inhibitors of the plasmodial surface anion channel (PSAC) inhibitors and the use thereof in treating or preventing malaria in an animal such as a human, comprising administering an effective amount of an inhibitor or a combination of inhibitors. An example of such an inhibitor is a compound of formula I, or a pharmaceutically acceptable salt thereof, wherein R 1 to R 7 are as described herein.
1. A method of providing prophylaxis to an animal against malaria or treating an animal afflicted with malaria comprising administering to the animal an effective amount of a compound of formula V:
wherein R 11 and R 12 are independently hydrogen, alkyl, cycloalkyl, or aryl which is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkoxy, halo, hydroxy, nitro, cyano, amino, alkylamino, aminoalkyl, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, and formyl;
R 13 is alkyl or alkoxy and R 14 and R 15 are hydrogen; or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein R 13 is methyl or methoxy.
3. The method of claim 1 , wherein R 11 is alkyl and R 12 is alkyl, cycloalkyl, or aryl, wherein said aryl is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkoxy, halo, hydroxy, nitro, cyano, amino, alkylamino, aminoalkyl, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl, and formyl.
4. The method of claim 3 , wherein R 12 is alkyl, cycloalkyl, or aryl, wherein said aryl is optionally substituted with one or more alkyl and/or alkoxy substituents.
5. The method of claim 4 , wherein the compound of formula V is:
6. The method of claim 1 , wherein R 11 is hydrogen and R 12 is cycloalkyl or aryl, which is optionally substituted with one or more alkyl and/or alkoxy substituents.
7. The method of claim 6 , wherein the compound of formula V is:
8. The method of claim 1 , wherein said animal is a human.
9. The method of claim 1 , wherein a compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof is administered in combination with
or a pharmaceutically acceptable salt thereof.
10. The method of claim 1 , wherein a compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof is administered in combination with
or a pharmaceutically acceptable salt thereof.
11. The method of claim 1 , wherein
or a pharmaceutically acceptable salt thereof is administered in combination with
or a pharmaceutically acceptable salt thereof.
12. The method of claim 1 , wherein
or a pharmaceutically acceptable salt thereof is administered in combination with
or a pharmaceutically acceptable salt thereof.
13. The method of claim 1 , which involves a further administration of a compound of the formula:
or a pharmaceutically acceptable salt thereof.