Compounds and compositions for the treatment of parasitic diseases

1. A method for treating the pathology and/or symptomology of a disease caused by a parasite, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (A), or a pharmaceutically acceptable salt, or stereoisomer thereof; and further comprising administering a second agent;

wherein

Ring A is phenyl or pyridyl;

X is —C(O)— or —S(O) 2 —;

R 1 is selected from nitro, C 1-4 alkyl, C 1-6 alkoxy, amino, C 1-6 alkylamino, di-C 1-6 alkylamino, —N(C 2 H 3 ) 2 , C 3-6 cycloalkyl, C 4-6 heterocycloalkyl, C 4-8 heterocycloalkenyl, and C 5-9 heteroaryl, wherein the C 1-6 alkoxy, C 1-6 alkylamino, C 3-6 cycloalkyl, C 4-6 heterocycloalkyl, C 4-8 heterocycloalkenyl, or C 5-9 heteroaryl of R 1 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, diC 1-4 alkylamino, and hydroxycarbonyl, and C 1-4 alkylcarbonyl;

R 3 is selected from hydrogen, halo, cyano, C 1-4 alkyl, and haloC 1-4 alkyl, and n is 0, 1, or 2;

R 7 is selected from hydrogen or C 1-4 alkyl;

L 3 is a bond, phenylene, or C 5-6 heteroarylene;

R 0 is selected from hydrogen, hydroxyl, halo, nitro, —N═CHN(CH 3 ) 2 , C 1-4 alkyl, C 4-6 heterocycloalkylC 1-4 alkyl, C 1-4 alkoxy, —NR 2a R 2b , —NR 5 C(O)R 6 , —NR 5 S(O) 2 R 8 , —Si(CH 3 ) 3 , C 3-6 cycloalkyl, C 5-6 cycloalkenyl, C 4-6 heterocycloalkyl, C 5-8 heterocycloalkenyl, C 6-10 aryl, and C 5-6 heteroaryl; wherein

the C 1-4 alkyl or C 1-4 alkoxy of R 0 is unsubstituted or substituted by 1-2 substituents independently selected from C 1-4 alkoxy, amino, phenyl and C 5-6 heteroaryl; wherein the phenyl or C 5-6 heteroaryl substituent of R 0 is unsubstituted or further substituted by halo or C 1-4 alkyl;

the C 3-6 cycloalkyl, C 5-6 cycloalkenyl, C 4-6 heterocycloalkyl, C 5-8 heterocycloalkenyl, C 6-10 aryl, or C 5-6 heteroaryl of R 0 is unsubstituted or substituted by 1 to 4 substituents independently selected from halo, oxo, C 1-4 alkyl, hydroxyC 1-4 alkyl, haloC 1-4 alkyl, —(CH 2 ) 1-4 NR a R b , C 4-6 heterocycloalkylC 1-4 alkyl, benzyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, diC 1-4 alkylamino, unsubstituted C 4-6 heterocycloalkyl and C 1-4 alkyl substituted C 4-6 heterocycloalkyl, wherein R a and R b are each independently selected from hydrogen, C 1-4 alkyl, and C 3-6 cycloalkyl;

R 2a is hydrogen or C 1-4 alkyl;

R 2b is selected from hydrogen, C 1-4 alkyl and —C(O)OCH(CH 3 ) 2 , wherein the C 1-4 alkyl of R 2b is unsubstituted or substituted by amino, C 4-6 heterocycloalkyl, phenyl or C 5-6 heteroaryl, wherein the C 4-6 heterocycloalkyl, phenyl or C 5-6 heteroaryl substituent of R 2b is unsubstituted or substituted by hydroxyl, halo or C 1-4 alkyl;

R 5 is hydrogen or C 1-4 alkyl;

R 6 is selected from hydrogen, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyloxy, amino, C 3-6 cycloalkyl, C 5-6 heterocycloalkyl, and C 5-6 heteroaryl, wherein

the C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyloxy, or amino of R 6 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, hydroxyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, —NR 9a R 9b , C 3-6 cycloalkyl, C 5-6 heterocycloalkyl, and C 5-6 heteroaryl, wherein R 9a is hydrogen or C 1-4 alkyl, R 9b is selected from hydrogen, C 1-4 alkyl, C 1-4 alkylcarbonyl and C 1-4 alkoxycarbonyl, and the C 5-6 heterocycloalkyl or C 5-6 heteroaryl substituent of R 6 is each unsubstituted or substituted by 1-2 substituents independently selected from hydroxyl, C 1-4 alkyl and C 1-4 alkoxycarbonyl,

the C 3-6 cycloalkyl or C 5-6 heterocycloalkyl of R 6 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, cyano, hydroxyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxylC 1-4 alkyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, di-C 1-4 alkylamino, aminocarbonyl, C 1-4 alkoxycarbonyl, and C 1-4 alkoxycarbonylaminoC 1-4 alkyl, and

the C 5-6 heteroaryl of R 6 is unsubstituted or substituted by 1 to 2 substituents independently selected from hydroxyl, C 1-4 alkyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, di-C 1-4 alkylamino, and C 1-4 alkoxycarbonyl; and

R 8 is C 1-4 alkyl or C 1-4 alkylamino; and

wherein the disease is selected from leishmaniasis, human African trypanosomiasis and Chagas disease.

2. The method of claim 1 , wherein said compound of Formula (A) is capable of inhibiting the proteolytic activity of the proteasomes of said parasite.

3. The method of claim 1 , wherein said compound of Formula (A) is capable of inhibiting the chymotrypsin-like proteolytic activity of the proteasomes.

4. The method of claim 1 , wherein said compound of Formula (A) is of Formula Ia:

or a pharmaceutically acceptable salt, or stereoisomer thereof; wherein

R 1 is selected from C 1-4 alkoxy, di-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, or C 5-6 heteroaryl of R 1 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, C 1-4 alkyl, C 1-4 alkoxy, diC 1-4 alkylamino, and hydroxycarbonyl;

R 3 is halo;

R 0 is selected from hydrogen, halo, C 1-4 alkyl, —NR 2a R 2b , —Si(CH 3 ) 3 , C 3-6 cycloalkyl, C 5-6 cycloalkenyl, C 4-6 heterocycloalkyl, C 5-6 heterocycloalkenyl, phenyl, and C 5-6 heteroaryl; wherein

R 2a is hydrogen or C 1-4 alkyl;

R 2b is selected from hydrogen, C 1-4 alkyl, and —C(O)OCH(CH 3 ) 2 ; and

the C 3-6 cycloalkyl, C 5-6 cycloalkenyl, C 4-6 heterocycloalkyl, C 5-6 heterocycloalkenyl, phenyl, or C 5-6 heteroaryl of R 0 is unsubstituted or substituted by 1 to 4 substituents independently selected from halo, C 1-4 alkyl, haloC 1-4 alkyl, C 4-6 heterocycloalkylC 1-4 alkyl, benzyl, C 1-4 alkoxy, unsubstituted C 6 heterocycloalkyl, and C 1-4 alkyl substituted C 6 heterocycloalkyl.

5. The method of claim 4 , wherein

R 1 is oxazolyl or pyrrolidinyl, wherein the oxazolyl or pyrrolidinyl is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, C 1-4 alkyl, C 1-4 alkoxy, diC 1-4 alkylamino, and hydroxycarbonyl;

R 3 is fluoro or chloro;

R 0 is selected from C 1-4 alkyl, pyrrolidinyl, phenyl and pyridinyl, wherein the pyrrolidinyl, phenyl or pyridinyl is unsubstituted or substituted by one substituent selected from halo, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, unsubstituted C 6 heterocycloalkyl, and C 1-4 alkyl substituted C 6 heterocycloalkyl.

6. The method of claim 1 , wherein said compound of Formula (A) is selected from:

N-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2-methyloxazole-5-carboxamide;

2-(dimethylamino)-N-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)oxazole-5-carboxamide;

N-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)cyclobutanecarboxamide;

N-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)pyrrolidine-1-carboxamide;

(R)—N-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-3-methoxypyrrolidine-1-carboxamide;

3-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-1,1-dimethyl(deuterated) urea;

N-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-3,3-dimethylazetidine-1-carboxamide;

N-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)azetidine-1-carboxamide;

(R)-3-fluoro-N-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)pyrrolidine-1-carboxamide;

(2S,4R)-4-fluoro-1-((4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)carbamoyl)pyrrolidine-2-carboxylic acid;

3-fluoro-N-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)azetidine-1-carboxamide;

N-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-3-methylazetidine-1-carboxamide;

3,3-difluoro-N-(4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)azetidine-1-carboxamide;

Isopropyl (4-fluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)carbamate;

N-(4-chloro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)furan-2-carboxamide;

N-(4-chloro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)pyrrolidine-1-carboxamide;

N-(4-fluoro-3-(6-(pyridine-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(pyridine-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2-methyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(pyridine-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)azetidine-1-carboxamide;

N-(3-(6-(tert-butyl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-chloro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-chloro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2-methyloxazole-5-carboxamide;

N-(3-(6-chloro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)pyrrolidine-1-carboxamide;

N-(3-(6-chloro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-3-fluoroazetidine-1-carboxamide;

N-(3-(6-chloro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-3,3-difluoroazetidine-1-carboxamide;

(R)—N-(3-(6-chloro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-3-methoxypyrrolidine-1-carboxamide;

N-(3-(6-(3,6-dihydro-2H-pyran-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

3-(3-(6-(3,6-dihydro-2H-pyran-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-1,1-dimethylurea;

N-(3-(6-(3,6-dihydro-2H-pyran-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-3-fluoroazetidine-1-carboxamide;

N-(3-(6-(3,6-dihydro-2H-pyran-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)azetidine-1-carboxamide;

(R)—N-(3-(6-(3,6-dihydro-2H-pyran-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-3-fluoropyrrolidine-1-carboxamide;

N-(3-(6-bromo-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-chlorophenyl)furan-2-carboxamide;

N-(3-(6-cyclopropyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-(cyclopent-1-en-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(2,2,6,6-tetramethyl-3,6-dihydro-2H-pyran-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-en-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-(2,5-dihydro-1H-pyrrol-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(4-(2-morpholinoethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(2-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(5-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(1-methyl-1H-pyrazol-5-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(1-methyl-1H-pyrazol-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(2-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(6-methoxypyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-([1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(pyridine-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(6-methoxypyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(2-methoxypyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(6-(piperazin-1-yl)pyridine-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(6-(4-methylpiperazin-1-yl)pyridine-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(6-isopropoxypyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-(5-chloropyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(6-morpholinopyridin-3-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(3-fluoropyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(3-(trifluoromethyl)pyridine-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(3-methylpyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(3-methoxypyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(5-methylpyrazin-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(pyrazin-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-(3-chloropyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(trimethylsilyl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(piperidin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-morpholino-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-(ethyl(methyl)amino)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-(azetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(3-fluoroazetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(isopropyl(methyl)amino)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-(dimethylamino)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-(diethylamino)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-(3,3-difluoroazetidin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(pyrrolidin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

(R)—N-(4-fluoro-3-(6-(3-fluoropyrrolidin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(piperazin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(isopropylamino)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

Isopropyl (2-(5-(2,4-dimethyloxazole-5-carboxamido)-2-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)carbamate;

N-(4-fluoro-3-(6-(pyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-N,2,4-trimethyloxazole-5-carboxamide;

N-(4-fluoro-3-(6-(3-methylpyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-N,2,4-trimethyloxazole-5-carboxamide;

N-(3-(6-(3-(difluoromethyl)pyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(3-(6-(7-azabicyclo[2.2.1]hept-2-en-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-2,4-dimethyloxazole-5-carboxamide;

2,4-dimethyl-N-(4-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)pyridin-2-yl)oxazole-5-carboxamide;

2,4-dimethyl-N-(5-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)pyridin-3-yl)oxazole-5-carboxamide;

2,4-dimethyl-N-(2-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)pyridin-4-yl)oxazole-5-carboxamide;

N-(2,4-difluoro-3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

2,4-dimethyl-N-(6-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)pyridin-2-yl)oxazole-5-carboxamide;

N-(4-fluoro-3-(6-(pyrrolidin-1-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

N-(2,4-difluoro-5-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

(R)-3-fluoro-N-(3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)pyrrolidine-1-carboxamide;

(R)—N-(3-(6-chloro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-4-fluorophenyl)-3-fluoropyrrolidine-1-carboxamide;

N-(4-fluoro-3-(6-isopropyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide;

2,4-dimethyl-N-(3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)oxazole-5-carboxamide;

N-(3-(6-(3,6-dihydro-2H-pyran-4-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)-2,4-dimethyloxazole-5-carboxamide; and

(R)-3-fluoro-N-(3-(6-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)phenyl)pyrrolidine-1-carboxamide.

7. The method of claim 1 , wherein said compound is

or a pharmaceutically acceptable salt, or stereoisomer thereof.

8. The method of claim 1 , wherein said compound is

or a pharmaceutically acceptable salt, or stereoisomer thereof.

9. The method of claim 1 , wherein said compound is

or a pharmaceutically acceptable salt, or stereoisomer thereof.

10. The method of claim 1 , wherein said compound is

or a pharmaceutically acceptable salt, or stereoisomer thereof.

11. The method of claim 1 , wherein said compound is

or a pharmaceutically acceptable salt, or stereoisomer thereof.

12. The method of claim 1 , wherein said disease is leishmaniasis, and said second agent is selected from stibogluconate, meglumine antimoniate, Amphotericin, Miltefosine, and paromomycin.

13. The method of claim 1 , wherein said disease is human African trypanosomiasis, and said second agent is selected from pentamidine, suramin, melarsoprol, eflornithine, and nifurtimox.

14. The method of claim 1 , wherein said disease is Chagas disease, and said second agent is selected from benznidazole, nifurtimox and Amphotericin.

15. A combination comprising a therapeutically effective amount of a compound of Formula (A), or a pharmaceutically acceptable salt, or stereoisomer thereof, and a second therapeutic agent;

wherein

Ring A is phenyl or pyridyl;

X is —C(O)— or —S(O) 2 —;

R 1 is selected from nitro, C 1-4 alkyl, C 1-6 alkoxy, amino, C 1-6 alkylamino, di-C 1-6 alkylamino, —N(C 2 H 3 ) 2 , C 3-6 cycloalkyl, C 4-6 heterocycloalkyl, C 4-8 heterocycloalkenyl, and C 5-9 heteroaryl, wherein the C 1-6 alkoxy, C 1-6 alkylamino, C 3-6 cycloalkyl, C 4-6 heterocycloalkyl, C 5-9 heterocycloalkenyl, or C 5-9 heteroaryl of R 1 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, diC 1-4 alkylamino, and hydroxycarbonyl, and C 1-4 alkylcarbonyl;

R 3 is selected from hydrogen, halo, cyano, C 1-4 alkyl, and haloC 1-4 alkyl, and n is 0, 1, or 2;

R 7 is selected from hydrogen or C 1-4 alkyl;

L 3 is a bond, phenylene, or C 5-6 heteroarylene;

R 0 is selected from hydrogen, hydroxyl, halo, nitro, —N═CHN(CH 3 ) 2 , C 1-4 alkyl, C 4-6 heterocycloalkylC 1-4 alkyl, C 1-4 alkoxy, —NR 2a R 2b , —NR 5 C(O)R 6 , —NR 5 S(O) 2 R 8 , —Si(CH 3 ) 3 , C 3-6 cycloalkyl, C 5-6 cycloalkenyl, C 4-6 heterocycloalkyl, C 5-8 heterocycloalkenyl, C 6-10 aryl, and C 5-6 heteroaryl; wherein

the C 1-4 alkyl or C 1-4 alkoxy of R 0 is unsubstituted or substituted by 1-2 substituents independently selected from C 1-4 alkoxy, amino, phenyl and C 5-6 heteroaryl; wherein the phenyl or C 5-6 heteroaryl substituent of R 0 is unsubstituted or further substituted by halo or C 1-4 alkyl;

the C 3-6 cycloalkyl, C 5-6 cycloalkenyl, C 4-6 heterocycloalkyl, C 5-8 heterocycloalkenyl, C 6-10 aryl, or C 5-6 heteroaryl of R 0 is unsubstituted or substituted by 1 to 4 substituents independently selected from halo, oxo, C 1-4 alkyl, hydroxyC 1-4 alkyl, haloC 1-4 alkyl, —(CH 2 ) 1-4 NR a R b , C 4-6 heterocycloalkylC 1-4 alkyl, benzyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, diC 1-4 alkylamino, unsubstituted C 4-6 heterocycloalkyl and C 1-4 alkyl substituted C 4-6 heterocycloalkyl, wherein R a and R b are each independently selected from hydrogen, C 1-4 alkyl, and C 3-6 cycloalkyl;

R 2a is hydrogen or C 1-4 alkyl;

R 2b is selected from hydrogen, C 1-4 alkyl and —C(O)OCH(CH 3 ) 2 , wherein the C 1-4 alkyl of R 2b is unsubstituted or substituted by amino, C 4-6 heterocycloalkyl, phenyl or C 5-6 heteroaryl, wherein the C 4-6 heterocycloalkyl, phenyl or C 5-6 heteroaryl substituent of R 2b is unsubstituted or substituted by hydroxyl, halo or C 1-4 alkyl;

R 5 is hydrogen or C 1-4 alkyl;

R 6 is selected from hydrogen, C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyloxy, amino, C 3-6 cycloalkyl, C 5-6 heterocycloalkyl, and C 5-6 heteroaryl, wherein

the C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyloxy, or amino of R 6 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, hydroxyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, —NR 9a R 9b , C 3-6 cycloalkyl, C 5-6 heterocycloalkyl, and C 5-6 heteroaryl, wherein R 9a is hydrogen or C 1-4 alkyl, R 9b is selected from hydrogen, C 1-4 alkyl, C 1-4 alkylcarbonyl and C 1-4 alkoxycarbonyl, and the C 5-6 heterocycloalkyl or C 5-6 heteroaryl substituent of R 6 is each unsubstituted or substituted by 1-2 substituents independently selected from hydroxyl, C 1-4 alkyl and C 1-4 alkoxycarbonyl,

the C 3-6 cycloalkyl or C 5-6 heterocycloalkyl of R 6 is unsubstituted or substituted by 1 to 2 substituents independently selected from halo, cyano, hydroxyl, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxylC 1-4 alkyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, di-C 1-4 alkylamino, aminocarbonyl, C 1-4 alkoxycarbonyl, and C 1-4 alkoxycarbonylaminoC 1-4 alkyl, and

the C 5-6 heteroaryl of R 6 is unsubstituted or substituted by 1 to 2 substituents independently selected from hydroxyl, C 1-4 alkyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, di-C 1-4 alkylamino, and C 1-4 alkoxycarbonyl; and

R 8 is C 1-4 alkyl or C 1-4 alkylamino.