N3-substituted iminopyrimidinones as antimalarial agents
The present invention provides methods of treating malaria comprising administration of an N3-substituted iminopyrimidinone of Formula (I) or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the variables R 1 , R 2 , R 3 , R 4 , R 5 , A, B, L, m, and n are as defined herein. The invention also provides uses of the compounds of Formula (I), as defined herein, for inhibiting plasmepsin V activity, for treating a Plasmodium infection, and for treating malaria. Also provided are methods of treatment further comprising administration of one or more additional anti-malarial compounds.
1. A method for treating a Plasmodium infection, or for treating malaria, wherein the Plasmodium strain is drug resistant, consisting of administering to a subject in need of such treatment a therapeutically effective amount of a compound, and a pharmaceutically acceptable carrier, said compound having the structure:
or a pharmaceutically acceptable salt thereof.
2. The method according to claim 1 , wherein the compound has the structure:
or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the subject is human.
4. The method of claim 3 , wherein the compound or the pharmaceutically acceptable salt thereof is administered orally or via subcutaneous, intramuscular, or intravenous administration.
5. The method of claim 1 , wherein the method further consists of administration of one or more additional anti-malarial treatments to the subject.
6. The method of claim 5 , wherein the one or more additional anti-malarial treatment is selected from the group consisting of: artemether, lumefantrine, dihydroartemisinin, piperaquine, pyronaridine, artesunate, amodiaquine, mefloquine, sulfadoxine, pyrimethamine, lumefantrine, quinine, chloroquine, atovaquone, and proguanil.