IP Library › Granted Patent US 9,303,034

Granted Patent B2

US 9,303,034 · App. 14/574,775 · Granted Apr 5, 2016

Compounds and compositions for the treatment of parasitic diseases

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Patent No.: US 9,303,034
App. No.: 14/574,775
Granted: Apr 5, 2016
Kind: B2

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Abstract

The present invention provides compounds of Formula A: 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 parasite, such as leishmaniasis, human African trypanosomiasis and Chagas disease.

Claims (250)

1. A compound of Formula (A):

or a pharmaceutically acceptable salt, or stereoisomer thereof; 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 alkylalkyl, 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 s 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.

2. The compound of claim 1 , wherein the compound is of Formula (I):

or a pharmaceutically acceptable salt, or stereoisomer thereof; wherein

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 1-2 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;

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 5-6 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 -6 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 l -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 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,

3. The compound of claim 2 , wherein X is —C(O)—.

4. The compound according to claim 2 , wherein R 1 is selected from C 1-4 alkyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, diC 1-4 alkylamino, —N(C 2 H 3 ) 2 , C 3 -6 cycloalkyl, C 4-6 heterocycloalkyl, and C 5-6 heteroaryl, wherein

the C 1-4 alkoxy or C 1-4 alkylamino of R 1 is unsubstituted or substituted by 1 to 2 substituents independently selected from C 1-4 alkyl and C 1-4 alkoxy; and

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, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, di-4alkvlamino, and hydroxycarbonyl.

5. The compound according to claim 2 , wherein R 1 is selected from C 1-4 alkoxy, diC 1-4 alkylamino, —N(C 2 H 3 ) 2 , cyclobutyl, azetidinyl, pyrrolidinyl, furanyl and oxazolyl, wherein the cyclobutyl, azetidinyl, pyrrolidinyl, furanyl or oxazolyl 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.

6. The compound according to claim 2 , wherein R 3 is halo.

7. The compound according to claim 2 , wherein L 3 is a bond.

8. The compound according to claim 2 , wherein R 0 is selected from hydrogen, hydroxyl, halo, C 1-4 alkyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, diC 1-4 alkylamino, —NH(CH 2 ) 1-2 -phenyl, —NR 5 C(O)R 6 , —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

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, —(CH 2 ) 1-4 OH, 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 6 heterocycloalkyl and C 1-4 alkyl substituted C 6 heterocycloalkyl, wherein R a and R b are each independently selected from hydrogen, C 1-4 alkyl and C 3-6 cycloalkyl;

R 5 is hydrogen or C 1-4 alkyl; and

R 6 is selected from C 1-4 alkyl, C 1-4 alkoxy, C 3-6 cycloalkyl, C 5-6 heterocycloalkyl, and C 5-6 heteroaryl, each of which is unsubstituted or substituted by 1 to 2 substituents independently selected from hydroxyl, C 1-4 alkykl, C 1-4 alkoxy, amino, and C 1-4 alkylamino.

9. The compound according to claim 2 , R 0 is selected from hydrogen, chloro, bromo, tert-butyl, isopropylamino, isopropoxycarbonylamino, methylethylamino, methylisopropylamino, dimethyamino, diethylamino, —Si(CH 3 ) 3 , cyclopropyl, cyclopentenyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 2,5-dihydro-1H-pyrrolyl, 1,2,5,6-tetrahydropyridinyl, azabicyclo[3,2,1]oct-3-en-3-yl, 3,6-dihydro-2H-pyranyl, pyrazolyl, phenyl, pyridinyl, and pyrazinyl; wherein the cyclopropyl, cyclopentenyl, azetidinyl, pyrrolidinyl, piperidinyl, azabicyclo[3,2,1]oct-3-en-3-yl, piperazinyl, morpholinyl, 2,5-dihydro-1H-pyrrolyl, 1,2,5,6-tetrahydropyridinyl, 3,6-dihydro-2H-pyranyl, pyrazolyl, phenyl, pyridinyl, or pyrazinyl is unsubstituted or substituted by 1 to 4 substituents independently selected from fluoro, chloro, C 1-4 alkyl, trifluoromethyl, morpholinylethyl, benzyl, C 1-4 alkoxy, piperazinyl, N-methylpiperazinyl, and morpholinyl.

10. The compound according to claim 2 , wherein the compound is represented by 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

11. The compound according to claim 10 , 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.

12. A compound, or a pharmaceutically acceptable salt, or stereoisomer thereof; selected from:

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

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

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

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

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

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

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

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

13. A compound, or a pharmaceutically acceptable salt, or stereoisomer thereof;

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-2yl)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- 0 -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-fluorophenyhazetidine-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-chlorophenyhfuran-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-(2,2,6,6-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-yhphenyl)-2,4-dimethyloxazole-5-carboxamide;