Compounds and compositions for the treatment of parasitic diseases

Abstract

The present invention provides compounds of formula I: or a pharmaceutically acceptable salt, tautomer, or stereoisomer, thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds and methods of using such compounds for treating, preventing, inhibiting, ameliorating, or eradicating the pathology and/or symptomology of a disease caused by a Plasmodium parasite, such as malaria.

We claim: 
     
         1 . A compound of Formula I, 
       
         
           
           
               
               
           
         
       
       or a pharmaceutical acceptable salt, tautomer or stereoisomer thereof, wherein
 n is 0, 1, 2 or 3; 
 p is 0, 1, 2 or 3; 
 L is selected from the group consisting of *—(CHR 3 ) 1-3 —, *—CHR 3 N(R 2 )—, *—CHR 3 O—, *—CHR 3 S—, *—CHR 3 S(O)—, *—CHR 3 N(R 2 )CHR 3 —, *—C(O)—, *—C(O)N(R 2 )—, *—C(O)N(R 2 )CHR 3 —, *—N(R 2 )—, *—N(R 2 )CHR 3 —, *—N(R 2 )C(O)—, *—N(R 2 )C(O)N(R 2 )—, *—N(R 2 )S(O) 2 —, wherein
 * represents the point of attachment of L to the pyrazolo[1,5-a]pyridine fused ring depicted in Formula I; 
 each R 2  is independently selected from the group consisting of hydrogen, C 1-6 alkyl, haloC 1-6 alkyl, R—C 0-4 alkylene, and R—C 0-4 alkylene-C(O)—, wherein R is selected from the group consisting of hydroxyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, C 3-6 cycloalkyl, C 4-6 heterocycloalkyl, and C 5-6 heteroaryl, wherein the C 3-6 cycloalkyl, C 4-6 heterocycloalkyl, and C 5-6 heteroaryl of R are each unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of halo, amino, hydroxyl, C 1-4 alkyl, C 1-4 alkoxy, oxo, and C 5-6 heteroaryl; and 
 each R 3  is independently selected from the group consisting of hydrogen and C 1-4 alkyl; 
 
 Ring A is selected from the group consisting of C 6-10 aryl and C 3-10 heteroaryl; 
 Ring C is selected from the group consisting of C 6-10 aryl, C 5-10 heteroaryl, C 3-7 cycloalkyl, C 5-7 heterocycloalkyl, and fused bicyclyl comprising a C 5-6 heterocycloalkyl fused to a phenyl; 
 each R 1  is independently selected from the group consisting of halo, cyano, amino, C 1-4 alkyl, C 1-4 alkoxyl, halo-C 1-4 alkyl, —C(O)NR 7 R 8 , —NHC(O)R 11 , phenyl, and C 5-6 heteroaryl; wherein
 the phenyl and C 5-6 heteroaryl of R 1  are each unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of C 1-4 alkyl, amino, halo, and C 1-4 alkylamino; 
 R 7  and R 8  are each independently selected from hydrogen, C 1-4 alkyl and haloC 1-4 alkyl; 
 R 11  is C 1-6 alkyl, unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of amino, C 3-6 cycloalkyl and C 4-6 heterocycloalkyl; 
 
 R 17  is selected from the group consisting of cyano, halo, C 1-4 alkyl, halo-C 1-4 alkyl, oxo, C 3-6 cycloalkyl, and —SO 2 —C 1-4 alkyl. 
 
     
     
         2 . The compound of  claim 1 , wherein L is selected from the group consisting of *—C(O)N(R 2 )— and *—N(R 2 )C(O)—, wherein each R 2  is independently selected from hydrogen, C 1-4 alkyl, and R—C 0-4 alkylene, and wherein R is selected from the group consisting of C 4-6 heterocycloalkyl and C 5-6 heteroaryl, each of which is unsubstituted or substituted with 1-2 substituents independently selected from the group consisting of halo, amino, hydroxyl, C 1-4 alkyl, C 1-4 alkoxy, oxo, and C 5-6 heteroaryl. 
     
     
         3 . The compound of  claim 1 , wherein L is selected from the group consisting of *—CH(CH 3 )—, *—CH 2 CH 2 —, *—CH 2 N(CH 3 )—, *—CH 2 N(C(O)(CH 2 ) 1-2 NH(CH 3 ))—, *—CH 2 N(C(O)—(CH 2 ) 1-2 NH 2 )—, *—CH 2 N((C(O)—(CH 2 ) 1-2 N(CH 3 ) 2 )—, *—CH 2 N(C(O)(CH 2 ) 1-2 OH)—, *—CH(CH 3 )N(CH 3 )—, *—CH 2 O—, *—CH 2 S—, *—CH 2 S(O)—, *—C(O)—, *—C(O)N(CH 3 )—, *—C(O)N(CH 2 CH 3 )—, *—C(O)N(CH(CH 3 ) 2 )—, *—C(O)N(C(CH 3 ) 3 )—, *—C(O)N(CH 2 CH(CH 3 ) 2 )—, *—C(O)N(CH(CH 3 )CH 2 CH 3 )—, *—C(O)N(CH 2 CH 2 OCH 3 )—, *—C(O)N(CH 2 CH 2 N(CH 3 ) 2 )—, *—C(O)N(CH 3 )CH 2 —, *—NHCH 2 —, *—N(CH 3 )CH 2 —, *—N(CH 2 -tetrahydropyran-4-yl)-C(O)—, *—N(CH 3 )C(O)—, *—N(CH 3 )C(O)NH—, *—N(CH 3 )S(O) 2 —, *—C(O)N((CH 2 ) 0-1 -cyclopropyl)-, *—C(O)N((CH 2 ) 0-1 -cyclobutyl)-, *—C(O)N((CH 2 ) 0-1 -cyclopentyl)-, *—C(O)N((CH 2 ) 0-1 -cyclohexyl)-, *—C(O)N(CH 2 -tetrahydropyran-4-yl)-, *—C(O)N((CH 2 )-2-(1,1-dioxidothiomorpholino-4-yl))-, *—C(O)N(CH 2 -1,1-dioxidothiomorpholino-4-yl)-, *—C(O)N((CH 2 )-2-tetrahydropyran-4-yl)), *—C(O)N((CH 2 ) 1-2 -morpholin-4-yl)-, *—C(O)N(oxetan-3-yl)-, *—C(O)N(CH 2 -oxetan-3-yl)-, *—C(O)N(CH(CH 3 )—CH 2 -1-H-pyrazoly-1-yl)-, *—CH 2 N(C(O)—(CH 2 ) 1-2 -morpholinyl))-, *—CH 2 N(C(O)—(CH 2 ) 1-2 -4-methylpiperizin-1-yl)), *—CH 2 N(C(O)—(CH 2 ) 1-2 -tetrahydropyran-4-yl)-, and *—CH 2 N(C(O)(CH 2 ) 1-2 -oxetan-3-yl)-. 
     
     
         4 . The compound according to  claim 1 , wherein Ring A is selected from the group consisting of phenyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolopyridinyl, and indazolyl, each of which is unsubstituted or substituted by (R 1 ) n . 
     
     
         5 . The compound according to  claim 1 , wherein Ring C is selected from the group consisting of 
       
         
           
           
               
               
           
         
       
       each of which is unsubstituted or substituted by (R 17 ) p . 
     
     
         6 . The compound according to  claim 1 , wherein Ring C is selected from the group consisting of phenyl and pyridinyl, each of which is unsubstituted or substituted by (R 17 ) p . 
     
     
         7 . The compound according to  claim 1 , wherein each R 1  is independently selected from the group consisting of trifluoromethyl, cyano, —NH 2 —, —C(O)NH 2 , —C(O)NHCH 3 , —C(O)N(CH 3 ) 2 , and —NHC(O)CH(NH 2 )(CH 3 ). 
     
     
         8 . The compound according to  claim 1 , wherein each R 17  is independently selected from the group consisting of cyano, halo, C 1-4 alkyl, haloC 1-4 alkyl, —SO 2 —C 1-4 alkyl, and C 3-6 cycloalkyl. 
     
     
         9 . The compound of  claim 1 , wherein the compound is of Formula Ia: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutical acceptable salt, tautomer or stereoisomer thereof, wherein
 n is 1 or 2; 
 p is 1 or 2; 
 Ring A is phenyl, pyridinyl, or pyrimidinyl; 
 Ring C is phenyl or pyridinyl; 
 L is *—C(O)NR 2 — or *—NR 2 C(O)—, wherein R 2  is selected from hydrogen, C 1-4 alkyl, C 3-6 cycloalkyl-(C 0-4 )alkylene, C 4-6 heterocycloalkyl-(C 0-4 )alkylene, wherein the C 4-6 heterocycloalkyl is selected from the group consisting of piperazinyl, morpholinyl, thiomorpholinyl, tetrahydropyranyl, and oxetanyl, and wherein the C 3-6 cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; 
 each R 1  is independently *—C(O)NR 7 R 8  or —NH 2 —, wherein R 7  and R 8  are each independently hydrogen or C 1-4 alkyl; and 
 R 17  is selected from the group consisting of cyano, halo, —NH 2 —, —C(O)NH 2 , —C(O)NH(CH 3 ), and —C(O)N(CH 3 ) 2 . 
 
     
     
         10 . The compound of  claim 1 , wherein the compound, or a pharmaceutical acceptable salt, tautomer or stereoisomer thereof, is selected from the group consisting of:
 N-(4-cyanophenyl)-N-methyl-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   4-fluoro-N-methyl-N-((3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)methyl)aniline;   N-(4-chlorophenyl)-N-methyl-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(4-fluorophenyl)-N-methyl-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-methyl-N-(5-methylpyridin-2-yl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   4-chloro-N-methyl-N-((3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)methyl)aniline;   N,5-dimethyl-N-((3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)methyl)pyridine-2-amine;   5-((4-fluorophenoxy)methyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine;   N-(4-cyanophenyl)-N-(2-methoxyethyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(4-cyanophenyl)-N-(2-(dimethylamino)ethyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(4-cyanophenyl)-N-((tetrahydro-2H-pyran-4-ylmethyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(4-(methylsulfonyl)phenyl)-N-((tetrahydro-2H-pyran-4-ylmethyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(5-cyanopyridin-2-yl)-N-methyl-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-methyl-N-(5-methylpyridin-3-yl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   5-(((5-methylpyridin-2-yl)oxy)methyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine;   5-(4-fluorophenethyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine;   N-(4-cyanophenyl)-N-methyl-3-(1-methyl-1H-indazol-5-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;   3-(6-acetamidopyridin-3-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(4-carbamoylphenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(4-carbamoylphenyl)-N-(4-fluorophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   5-(((4-fluorophenyl)thio)methyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine;   5-(((4-fluorophenyl)sulfinylmethyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine;   3-(4-(1H-pyrazol-5-yl)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   N-(4-cyanophenyl)-N-methyl-3-(5-(trifluoromethyl)pyridine-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(5-cyanopyridin-2-yl)-N-methyl-3-(5-(trifluoromethyl)pyridine-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;   (S)-3-(4-(2-aminopropanamido)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(5-carbamoylpyridin-2-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   4-cyano-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)benzamide;   4-fluoro-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)benzamide;   4-cyano-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-yl)benzenesulfonamide;   4-fluoro-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-yl)benzenesulfonamide;   3-(4-carbamoylphenyl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide; N-methyl-3-(4-(trifluoromethyl)phenyl)-N-(5-(trifluoromethyl)yridine-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-methyl-N-(5-(methylsulfonyl)pyridine-2-yl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(4-fluorobenzyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-amine   N-(4-fluorobenzyl)-3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-amine;   N-methyl-6-(trifluoromethyl)-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)nicotinamide;   N-methyl-5-(trifluoromethyl)-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]yridine-5-yl)picolinamide;   4-cyano-N-((tetrahydro-2H-pyran-4-ylmethyl)-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)benzamide;   N-(4-cyanophenyl)-N-methyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;   3-(6-aminopyridin-3-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(4-aminophenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(4-(2-aminoacetamido)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   (R)-3-(4-(2-aminopropanamido)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   (S)-3-(4-(2-amino-3-methylbutanamido)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   (S)-3-(4-(2-amino-2-cyclohexylacetamido)phenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(4-fluorophenyl)-1-methyl-1-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)urea;   6-(1,1-difluoroethyl)-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)nicotinamide;   6-cyclopropyl-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)nicotinamide;   4-cyclopropyl-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)benzamide;   5-fluoro-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)picolinamide;   N-methyl-4-(methylsulfonyl)-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)benzamide;   N-(5-cyanopyridin-2-yl)-N-methyl-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;   3-(6-aminopyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   4-chloro-N-methyl-N-(3-(4-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)benzamide;   N-(3-(4-carbamoylphenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-fluoro-N-methylbenzamide   4-fluoro-N-methyl-N-(3-(4-(5-(methylamino)-1,3,4-thiadiazol-2-yl)phenyl)pyrazolo[1,5-a]pyridin-5-yl)benzamide;   N-methyl-N-(5-(methylsulfonyl)pyridin-2-yl)-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(5-cyanopyridin-2-yl)-N-methyl-3-(5-methylpyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(5-cyanopyridin-2-yl)-3-(5-methoxypyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(5-carbamoylpyridin-2-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(4-carbamoylphenyl)-N-methyl-N-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;   3-(4-carbamoylphenyl)-N-methyl-N-(5-methylpyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(4-fluorophenyl)-N-methyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   4-(5-(1-(methyl(5-methylpyridin-2-yl)amino)ethyl)pyrazolo[1,5-a]pyridin-3-yl)benzamide;   4-(5-(1-(7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)ethyl)pyrazolo[1,5-a]pyridin-3-yl)benzamide;   N-(4-cyanophenyl)-N-methyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(4-(5-(1-(methyl(5-methylpyridin-2-yl)amino)ethyl)pyrazolo[1,5-a]pyridin-3-yl)phenyl)acetamide;   3-(4-acetamidophenyl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   4-(5-(7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-4-carbonyl)pyrazolo[1,5-a]pyridin-3-yl)benzamide;   4-(5-(7-fluoro-3-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-4-carbonyl)pyrazolo[1,5-a]pyridin-3-yl)benzamide;   4-(5-(7-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-4-carbonyl)pyrazolo[1,5-a]pyridin-3-yl)-N-methylbenzamide;   4-(5-(7-fluoro-3-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-4-carbonyl)pyrazolo[1,5-a]pyridin-3-yl)-N-methylbenzamide;   N-(5-cyanopyridin-2-yl)-N-methyl-3-(4-(methylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(5-cyanopyridin-2-yl)-3-(4-(methylcarbamoyl)phenyl)-N-(oxetan-3-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;   N-(1-(1H-pyrazol-1-yl)propan-2-yl)-3-(4-carbamoylphenyl)-N-(5-cyanopyridin-2-yl)pyrazolo[1,5-a]pyridine-5-carboxamide;   3-(6-amino-5-fluoropyridin-3-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(4-amino-3,5-dimethylphenyl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(6-amino-5-methylpyridin-3-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(4-carbamoylphenyl)-N-(4-cyanocyclohexyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(2-aminopyrimidin-5-yl)-N-(4-cyanophenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(6-amino-5-cyanopyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(6-amino-5-chloropyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(6-amino-5-(dimethylcarbamoyl)pyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide;   3-(6-amino-5-methoxypyridin-3-yl)-N-(5-cyanopyridin-2-yl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide; and   3-(4-carbamoylphenyl)-N-(4-chloro-2-formylphenyl)-N-methylpyrazolo[1,5-a]pyridine-5-carboxamide.   
     
     
         11 . A pharmaceutical composition comprising at least one compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         12 . The pharmaceutical composition according to  claim 11 , further comprising a second agent, wherein the second agent is an antimalarial drug selected from artemisinin, artemether, artesunate, arteflene, dihydroartemisinin, chlorproguanil, trimethoprim, chloroquine, quinine, mefloquine, amodiaquine, atovaquone, proguanil, lumefantrine, piperaquine, pyronaridine, halofantrine, pyrimethamine-sulfadoxine, quinacrine, pyrimethamine-dapsone, quinidine, amopyroquine, sulphonamides, primaquine, ferroquine, tafenoquine, arterolane, and pyronaridine. 
     
     
         13 . A method for treating, preventing, inhibiting, ameliorating, or eradicating the pathology and/or symptomology of a disease caused by a  Plasmodium  parasite, comprising administering to a subject a therapeutically effective amount of a compound according to  claim 1  or a composition according to  claim 11 , wherein the administering may be in combination with a second agent. 
     
     
         14 . The method according to  claim 13 , wherein the disease is malaria. 
     
     
         15 . The method according to  claim 13 , wherein the  Plasmodium  parasite is at the blood stages. 
     
     
         16 . The method according to  claim 13 , wherein the  Plasmodium  parasite is at the hepatic stages. 
     
     
         17 . The method of  claim 14 , wherein the  Plasmodium  parasite is selected from group consisting of  Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale , and  Plasmodium malaria.    
     
     
         18 . The method according to  claim 13 , wherein the second agent is selected from a kinase inhibitor, an anti-malarial drug and an anti-inflammatory agent. 
     
     
         19 . The method according to  claim 18 , wherein the anti-malarial drug is selected from artemisinin, artemether, artesunate, arteflene, dihydroartemisinin, chlorproguanil, trimethoprim, chloroquine, quinine, mefloquine, amodiaquine, atovaquone, proguanil, lumefantrine, piperaquine, pyronaridine, halofantrine, pyrimethamine-sulfadoxine, quinacrine, pyrimethamine-dapsone, quinidine, amopyroquine, sulphonamides, primaquine, ferroquine, tafenoquine, arterolane, and pyronaridine. 
     
     
         20 . The method according to  claim 18 , wherein the compound is administered prior to, simultaneously with, or after the second agent.