Compounds, compositions and associated methods comprising 3-aryl quinolines

Abstract

Compounds, compositions and methods useful for treating infectious diseases are provided. In particular, 3-aryl quinoline compounds, their synthesis, pharmaceutical compositions thereof and methods of treating infectious diseases such as malaria, are disclosed.

1 . A compound with the structure of Formula (II) 
       
         
           
           
               
               
           
         
       
       wherein R 1  is a substituted alkyl selected from N-isobutylpropanamino, N-isobutylethanamino, N—N-diethylpropanamino, N—N-diethyl-(4-methyl)butanamino, and 2-(2-piperidinyl) ethyl and X 1 , X 2 , X 3 , X 4 , and X 5  are independently selected from at least one of H, halo, alkoxy, ether, alkyl, substituted alkyl, alkyl ether, haloalkyl, haloalkyl ether, aryl, substituted aryl, aryl ether, substituted aryl ether, aryl amine, 5-member heterocycle, 6-member heterocycle, amino, benzylic amide, alkoxy, cyano, morpholinyl, N-ethyl morpholinyl, or carboxyl. 
     
     
         2 . (canceled) 
     
     
         3 . The compound of  claim 1 , wherein the compound has a structure selected from: 
       
         
           
           
               
               
           
         
       
     
     
         4 . A compound with the structure of Formula (III) 
       
         
           
           
               
               
           
         
         wherein n is an integer equal to 2 or 3; and 
         wherein X 2 , X 3 , and X 4  are independently H, halo, halomethyl, halomethoxy, haloethyl, haloethoxy, phenyl, phenyl ether, halomethoxy substituted phenyl, halomethoxy substituted phenyl ether, dimethylamino, cyano, morpholinyl, or N-morpholinyl ethyl. 
       
     
     
         5 . The compound of  claim 4 , wherein the compound has a structure selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         6 . A pharmaceutical composition comprising an effective amount of the compound of  claim 1 . 
     
     
         7 . The pharmaceutical composition of  claim 6  for use in the treatment of a parasitic infection. 
     
     
         8 . A method of treating a parasitic infection in a subject, the method comprising: administering a therapeutically effective amount of the pharmaceutical composition of  claim 6  to the subject. 
     
     
         9 . The method of  claim 8 , wherein the pharmaceutical composition is administered orally, subcutaneously, intravenously or intramuscularly. 
     
     
         10 . The method of  claim 8 , wherein the parasitic infection is a  Plasmodium  infection. 
     
     
         11 . The method of  claim 10 , wherein the  Plasmodium  infection comprises an infection with a  plasmodium  strain resistant to one or more of the following classes of compounds: quinine, mefloquine, chloroquine, or atovaquone. 
     
     
         12 . The method of  claim 10 , wherein the  Plasmodium  strain is selected from  P. falciparum  and  P. yoelii.    
     
     
         13 . The method of  claim 8 , wherein the pharmaceutical composition comprises a compound with a structure selected from 
       
         
           
           
               
               
           
         
       
     
     
         14 . A pharmaceutical composition comprising an effective amount of the compound of  claim 3 . 
     
     
         15 . A pharmaceutical composition comprising an effective amount of the compound of  claim 4 . 
     
     
         16 . A pharmaceutical composition comprising an effective amount of the compound of  claim 5 . 
     
     
         17 . The method of  claim 9 , wherein the pharmaceutical composition comprises a compound with a structure selected from 
       
         
           
           
               
               
           
         
       
     
     
         18 . The method of  claim 10 , wherein the pharmaceutical composition comprises a compound with a structure selected from 
       
         
           
           
               
               
           
         
       
     
     
         19 . The method of  claim 11 , wherein the pharmaceutical composition comprises a compound with a structure selected from 
       
         
           
           
               
               
           
         
       
     
     
         20 . The method of  claim 12 , wherein the pharmaceutical composition comprises a compound with a structure selected from