Method of Treating or Inhibiting Malaria

Abstract

Disclosed are derivative compounds of ELQ-300 that include an ester at position 4. These compounds have enhanced properties relative to ELQ-300. Also disclosed are pharmaceutical compositions comprising the compounds and methods of treating and preventing malaria infections involving administering the pharmaceutical compositions to the subject.

1 - 12 . (canceled) 
     
     
         13 . A method of treating or inhibiting malaria in a human, the method comprising administering to the human in need thereof a therapeutically effective amount of a compound selected from the group of: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         14 . The method of  claim 13 , wherein the malaria is chloroquine-resistant malaria. 
     
     
         15 . The method of  claim 13 , wherein the malaria is multidrug-resistant malaria. 
     
     
         16 . The method of  claim 15 , wherein the multidrug-resistant malaria is caused by resistance to two or more agents selected from the group of chloroquine, quinine, mefloquine, pyrimethamine, dapsone, atovaquone, or a  P. falciparum  DHOD inhibitor; or a pharmaceutically acceptable salt thereof. 
     
     
         17 . The method of  claim 13 , wherein the method further comprises co-administering with the compound of claim  1 , or a pharmaceutically acceptable salt thereof, to the human in need thereof a therapeutically effective amount of one or more compounds selected from the group of quinine, chloroquine, atovaquone, proguanil, primaquine, amodiaquine, mefloquine, piperaquine, artemisinin, artesunate, methylene blue, pyrimethamine, sulfadoxine, artemether-lumefantrine, dapsone-chlorproguanil, artesunate, quinidine, clopidol, and ihydroartemisinin, or a pharmaceutically acceptable salt thereof. 
     
     
         18 . The method of  claim 13  comprising administering the compound, or a pharmaceutically acceptable salt thereof, to the human in need thereof prophylactically. 
     
     
         19 . The method of  claim 13 , wherein the human in need thereof has a latent malaria infection. 
     
     
         20 . A method of treating or inhibiting malaria in a human, the method comprising administering to the human in need thereof a therapeutically effective amount of a compound of the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         21 . The method of  claim 20 , wherein the malaria is chloroquine-resistant malaria. 
     
     
         22 . The method of  claim 20 , wherein the malaria is multidrug-resistant malaria. 
     
     
         23 . The method of  claim 22 , wherein the multidrug-resistant malaria is caused by resistance to two or more agents selected from the group of chloroquine, quinine, mefloquine, pyrimethamine, dapsone, atovaquone, or a  P. falciparum  DHOD inhibitor; or a pharmaceutically acceptable salt thereof. 
     
     
         24 . The method of  claim 20 , wherein the method further comprises co-administering with the compound of claim  1 , or a pharmaceutically acceptable salt thereof, to the human in need thereof a therapeutically effective amount of one or more compounds selected from the group of quinine, chloroquine, atovaquone, proguanil, primaquine, amodiaquine, mefloquine, piperaquine, artemisinin, artesunate, methylene blue, pyrimethamine, sulfadoxine, artemether-lumefantrine, dapsone-chlorproguanil, artesunate, quinidine, clopidol, and ihydroartemisinin, or a pharmaceutically acceptable salt thereof. 
     
     
         25 . The method of  claim 20  comprising administering the compound, or a pharmaceutically acceptable salt thereof, to the human in need thereof prophylactically. 
     
     
         26 . The method of  claim 20 , wherein the human in need thereof has a latent malaria infection.