Heteroaryl derivative compounds, and uses thereof

1. A compound represented by the following Chemical Formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof:

in the Chemical Formula 1,

X 1 to X 3 are each independently CH or N;

R X is —H, —C 1-6 alkyl, —C 1-6 aminoalkyl, —NH 2 , —NH(—C 1-6 alkyl), or —N(—C 1-6 alkyl)(—C 1-6 alkyl);

Y is —C 1-6 alkyl, —(CH 2 ) n aryl, —(CH 2 ) hydroaryl, —(CH 2 ) n heteroaryl, or —(CH 2 ) n hydroheteroaryl in which at least one H of the —(CH 2 ) n aryl, —(CH 2 ) hydroaryl, —(CH 2 ) n heteroaryl, or —(CH 2 ) n hydroheteroaryl ring may be substituted with —C 1-6 alkyl, —C 1-6 aminoalkyl, —C 1-6 hydroxyalkyl, —C 1-6 haloalkyl, —C 1-6 alkyl-O—C 1-6 alkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —CN, —(C═O)NR 1 R 2 , —(C═O)OR 3 , —NR 4 R 5 , —OR 6 , -halo, ═O, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein at least one H of the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl may be substituted with —C 1-6 alkyl, —C 1-6 haloalkyl, or -halo;

n is 0, 1, 2, 3, or 4;

R 1 to R 3 are each independently —H, —C 1-6 alkyl, or cycloalkyl;

R 4 and R 5 are each independently —H or —C 1-6 alkyl;

R 6 is —H, —C 1-6 alkyl, or phenyl in which at least one H of the phenyl ring may be substituted with —C 1-6 alkyl, —C 1-6 haloalkyl, or halo;

R Y1 to R Y5 are each independently —H or —C 1-6 alkyl, or R Y2 and R Y3 may be linked to each other to form cycloalkyl or heterocycloalkyl, R Y4 and R Y5 may be linked to each other to form cycloalkyl or heterocycloalkyl, and R Y3 and R Y4 may be linked to each other to form aryl or heteroaryl;

L is —(CH 2 )m-, —C(═O)—, or null;

m is 0, 1, 2, 3, or 4;

a ring Z is phenyl, 5- to 6-membered heteroaryl, 9- to 10-membered hydroheteroaryl, 3- to 5-membered cycloalkyl, or 6-membered heterocycloalkyl in which at least one H of the phenyl, 5- to 6-membered heteroaryl, 9- to 10-membered hydroheteroaryl, 3- to 5-membered cycloalkyl, or 6-membered heterocycloalkyl ring may be substituted with —C 1-6 alkyl, —C 1-6 cyanoalkyl, C 1-6 haloalkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —CN, —OH, —O—C 1-6 alkyl, —O—C 1-6 haloalkyl, —S—C 1-6 alkyl, —C(═O)—C 1-6 alkyl, —C(═O)—C 1-6 haloalkyl, —C(═O)O—C 1-6 alkyl, —S(═O) 2 —C 1-6 alkyl, —C(═N—O—C 1-6 alkyl)(C 1-6 alkyl), ═O, -halo, or Z 1 , wherein at least one H of the phenyl in the meta position relative to the L is unsubstituted or substituted with at least one selected from the group consisting of —C 1-6 alkyl, —C 1-6 cyanoalkyl, —C 1-6 haloalkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —O—C 1-6 alkyl, —O—C 1-6 haloalkyl, —C(═O)—C 1-6 alkyl, —S(═O) 2 —C 1-6 alkyl, —C(═N—O—C 1-6 alkyl)(C 1-6 alkyl), -halo, and Z 1 when the ring Z is phenyl, or two or more substituents of the phenyl, 5- to 6-membered heteroaryl, 9- to 10-membered hydroheteroaryl, 3- to 5-membered cycloalkyl, or 6-membered heterocycloalkyl ring may be linked to each other to form a fused ring or a spiro ring, wherein at least one H of the fused ring or spiro ring may be substituted with —C 1-6 alkyl or Z 1 ;

Z 1 is cycloalkyl, heterocycloalkyl, heterobicycloalkyl, heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, —NH-heterocycloalkyl, aryl, or heteroaryl in which the heterocycloalkyl, heterobicycloalkyl, heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, or —NH-heterocycloalkyl contains, in the ring, at least one selected from the group consisting of N, O, P, P(═O) and S, and at least one H of the heterocycloalkyl, heterobicycloalkyl, heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, —NH-heterocycloalkyl, aryl, or heteroaryl ring may be substituted with —C 1-6 alkyl, —C 1-6 aminoalkyl, —C 1-6 haloalkyl, —C 1-6 alkyl-NH—C 1-6 alkyl, —C 1-6 alkyl-N(C 1-6 alkyl)(C 1-6 alkyl), —C 1-6 alkenyl, —C 1-6 alkynyl, —C(═O)—C 1-6 alkyl, —C 1-6 alkyl-C(═O)—C 1-6 alkyl, —S(═O) 2 —C 1-6 alkyl, —C 1-6 alkyl-S(═O) 2 —C 1-6 alkyl, ═O, —NR 9 R 10 , -halo, cycloalkyl, or Z 2 ;

R 9 and R 10 are each independently —H or —C 1-6 alkyl;

Z 2 is heterocycloalkyl, heterobicycloalkyl, heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, —NH-heterocycloalkyl, aryl, or heteroaryl in which the heterocycloalkyl, heterobicycloalkyl, heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, or —NH-heterocycloalkyl contains, in the ring, at least one selected from the group consisting of N, O, P, P(═O) and S, and at least one H of the heterocycloalkyl, heterobicycloalkyl, heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, —NH-heterocycloalkyl, aryl, or heteroaryl ring may be substituted with —C 1-6 alkyl, —C 1-6 aminoalkyl, —C 1-6 hydroxyalkyl, —C 1-6 haloalkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —C(═O)—C 1-6 alkyl, —C 1-6 alkyl-S(═O) 2 —C 1-6 alkyl, ═O, —NR 11 R 12 , cycloalkyl, or Z 3 ;

R 11 and R 12 are each independently —H or —C 1-6 alkyl; and

Z 3 is heterocycloalkyl, heterobicycloalkyl, heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, or —NH-heterocycloalkyl in which the heterocycloalkyl, heterobicycloalkyl, heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, or —NH-heterocycloalkyl contains, in the ring, at least one selected from the group consisting of N, O, P, P(═O) and S, and at least one H of the heterocycloalkyl, heterobicycloalkyl, heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, or —NH-heterocycloalkyl ring may be substituted with —C 1-6 alkyl or cycloalkyl.

2. The compound represented by Chemical Formula I, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of claim 1 , wherein

X 1 to X 3 are each independently CH or N;

R X is —H, —NH 2 , —NH(—C 1-6 alkyl), or —N(—C 1-6 alkyl)(—C 1-6 alkyl);

Y is —C 1-6 alkyl, —(CH 2 ) n aryl, —(CH 2 ) n heteroaryl, or —(CH 2 ) n hydroheteroaryl in which at least one H of the —(CH 2 ) n aryl, —(CH 2 ) n heteroaryl, or —(CH 2 ) n hydroheteroaryl ring may be substituted with —C 1-6 alkyl, —C 1-6 haloalkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —CN, —(C═O)NR 1 R 2 , —(C═O)OR 3 , —NR 4 R 5 , —OR 6 , -halo, ═O, heterocycloalkyl, aryl, or heteroaryl, wherein at least one H of the heterocycloalkyl, aryl, or heteroaryl may be substituted with -halo;

n is 0, 1, or 2;

R 1 to R 3 are each independently —H, —C 1-6 alkyl, or cycloalkyl;

R 4 and R 5 are each independently —H or —C 1-6 alkyl;

R 6 is —C 1-6 alkyl or phenyl in which at least one H of the phenyl ring may be substituted with —C 1-6 alkyl, —C 1-6 haloalkyl, or halo;

R Y1 to R Y5 are each independently —H or —C 1-6 alkyl, or R Y2 and R Y3 may be linked to each other to form cycloalkyl, and R Y3 and R Y4 may be linked to each other to form aryl;

L is —(CH 2 )m-, —C(═O)—, or null;

m is 0, 1, or 2;

Z 1 is cycloalkyl, heterocycloalkyl, heterobicycloalkyl, heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, —NH-heterocycloalkyl, or heteroaryl in which the heterocycloalkyl, heterobicycloalkyl, heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, or —NH-heterocycloalkyl contains, in the ring, at least one selected from the group consisting of N, O, P, P(═O) and S, and at least one H of the heterocycloalkyl, heterobicycloalkyl, heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, —NH-heterocycloalkyl, or heteroaryl ring may be substituted with —C 1-6 alkyl, —C 1-6 aminoalkyl, —C 1-6 haloalkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —C(═O)—C 1-6 alkyl, —C 1-6 alkyl-S(═O) 2 —C 1-6 alkyl, ═O, —NR 9 R 10 , -halo, cycloalkyl, or Z 2 ;

R 9 and R 10 are each independently —H or —C 1-6 alkyl;

Z 2 is heterocycloalkyl, heterobicycloalkyl, or —NH-heterocycloalkyl in which the heterocycloalkyl, heterobicycloalkyl, or —NH-heterocycloalkyl contains, in the ring, at least one selected from the group consisting of N, O, P, P(═O) and S, and at least one H of the heterocycloalkyl, heterobicycloalkyl, or —NH-heterocycloalkyl ring may be substituted with —C 1-6 alkyl, —C 1-6 hydroxyalkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —C(═O)—C 1-6 alkyl, —C 1-6 alkyl-S(═O) 2 —C 1-6 alkyl, ═O, —NR 11 R 12 , cycloalkyl, or Z 3 ;

R 11 and R 12 are each independently —H or —C 1-6 alkyl; and

Z 3 is heterocycloalkyl, heterobicycloalkyl, or —C 1-6 alkyl-heterocycloalkyl in which the heterocycloalkyl, heterobicycloalkyl, or —C 1-6 alkyl-heterocycloalkyl contains, in the ring, at least one selected from the group consisting of N, O, P, P(═O) and S, and at least one H of the heterocycloalkyl, heterobicycloalkyl, or —C 1-6 alkyl-heterocycloalkyl ring may be substituted with —C 1-6 alkyl or cycloalkyl.

3. The compound represented by Chemical Formula I, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of claim 1 , wherein

X 1 is N;

X 2 and X 3 are each independently CH or N; and

R X is —H, —NH 2 , or —NH(—C 1-6 alkyl).

4. The compound represented by Chemical Formula I, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of claim 1 , wherein

Y is —C 1-6 alkyl, —(CH 2 ) n aryl, —(CH 2 ) n heteroaryl, or —(CH 2 ) n hydroheteroaryl in which at least one H of the —(CH 2 ) n aryl, —(CH 2 ) n heteroaryl, or —(CH 2 ) n hydroheteroaryl ring may be substituted with —C 1-6 alkyl, —C 1-6 haloalkyl, —C 1-6 alkynyl, —CN, —(C═O)NH-cycloalkyl, —(C═O)O—C 1-6 alkyl, —N(C 1-6 alkyl)(C 1-6 alkyl), —O(C 1-6 alkyl), —O-phenyl, -halo, ═O, heterocycloalkyl, aryl, or heteroaryl, wherein at least one H of the heterocycloalkyl, aryl, or heteroaryl may be substituted with -halo;

n is 0 or 1; and

R Y1 to R Y5 are each independently —H or —C 1-6 alkyl, or R Y2 and R Y3 may be linked to each other to form 3- to 6-membered cycloalkyl, and R Y3 and R Y4 may be linked to each other to form phenyl.

5. The compound represented by Chemical Formula I, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of claim 1 , wherein

L is —(CH 2 )m-, —C(═O)—, or null;

m is 0 or 1;

a ring Z is phenyl, 5- to 6-membered heteroaryl, 9- to 10-membered hydroheteroaryl, 3- to 5-membered cycloalkyl, or 6-membered heterocycloalkyl in which at least one H of the phenyl, 5- to 6-membered heteroaryl, 9- to 10-membered hydroheteroaryl, 3- to 5-membered cycloalkyl, or 6-membered heterocycloalkyl ring may be substituted with —C 1-6 alkyl, —C 1-6 cyanoalkyl, —C 1-6 haloalkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —CN, —O—C 1-6 alkyl, —O—C 1-6 haloalkyl, —S—C 1-6 alkyl, —C(═O)—C 1-6 alkyl, —C(═O)—C 1-6 haloalkyl, —C(═O)O—C 1-6 alkyl, —S(═O) 2 -C 1-6 alkyl, —C(═N—O—C 1-6 alkyl)(C 1-6 alkyl), ═O, -halo, or Z 1 , wherein at least one H of the phenyl in the meta position relative to the L is unsubstituted or substituted with at least one selected from the group consisting of —C 1-6 alkyl, —C 1-6 cyanoalkyl, —C 1-6 haloalkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —O—C 1-6 alkyl, —O—C 1-6 haloalkyl, —C(═O)—C 1-6 alkyl, —S(═O) 2 —C 1-6 alkyl, —C(═N—O—C 1-6 alkyl)(C 1-6 alkyl), -halo, and Z 1 when the ring Z is phenyl, or two or more substituents of the phenyl, 5- to 6-membered heteroaryl, 9- to 10-membered hydroheteroaryl, 3- to 5-membered cycloalkyl, or 6-membered heterocycloalkyl ring may be linked to each other to form a fused ring or a spiro ring, wherein at least one H of the fused ring or spiro ring may be substituted with —C 1-6 alkyl or Z 1 ;

Z 1 is 3- to 7-membered cycloalkyl, 5- to 7-membered heterocycloalkyl, 6- to 10-membered heterobicycloalkyl, 6- to 10-membered heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, —NH-heterocycloalkyl, or heteroaryl in which the 5- to 7-membered heterocycloalkyl, 6- to 10-membered heterobicycloalkyl, 6- to 10-membered heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, or —NH-heterocycloalkyl contains, in the ring, at least one selected from the group consisting of N, O, P, P(═O) and S, and at least one H of the 5- to 7-membered heterocycloalkyl, 6- to 10-membered heterobicycloalkyl, 6- to 10-membered heterospiroalkyl, —C 1-6 alkyl-heterocycloalkyl, —(C═O)-heterocycloalkyl, —NH-heterocycloalkyl, or heteroaryl ring may be substituted with —C 1-6 alkyl, —C 1-6 aminoalkyl, —C 1-6 haloalkyl, —C 1-6 alkenyl, —C(═O)—C 1-6 alkyl, —C 1-6 alkyl-S(═O) 2 —C 1-6 alkyl, ═O, —N(C 1-6 alkyl)(C 1-6 alkyl), -halo, cycloalkyl, or Z 2 ;

Z 2 is 5- to 7-membered heterocycloalkyl, 6- to 10-membered heterobicycloalkyl, or —NH-heterocycloalkyl in which the 5- to 7-membered heterocycloalkyl, 6- to 10-membered heterobicycloalkyl, or —NH-heterocycloalkyl contains, in the ring, at least one selected from the group consisting of N, O, and S, and at least one H of the 5- to 7-membered heterocycloalkyl, 6- to 10-membered heterobicycloalkyl, or —NH-heterocycloalkyl ring may be substituted with —C 1-6 alkyl, —C 1-6 hydroxyalkyl, —C 1-6 alkenyl, —C 1-6 alkynyl, —C(═O)—C 1-6 alkyl, —C 1-6 alkyl-S(═O) 2 —C 1-6 alkyl, ═O, —N(C 1-6 alkyl)(C 1-6 alkyl), 3- to 7-membered cycloalkyl, or Z 3 ; and

Z 3 is 5- to 7-membered heterocycloalkyl, 6- to 10-membered heterobicycloalkyl, or —C 1-6 alkyl-heterocycloalkyl in which the 5- to 7-membered heterocycloalkyl, 6- to 10-membered heterobicycloalkyl, or —C 1-6 alkyl-heterocycloalkyl contains, in the ring, at least one selected from the group consisting of N, O, and S, and at least one H of the 5- to 7-membered heterocycloalkyl, 6- to 10-membered heterobicycloalkyl, or —C 1-6 alkyl-heterocycloalkyl ring may be substituted with —C 1-6 alkyl or 3- to 7-membered cycloalkyl.

6. A compound, an optical isomer thereof, or a pharmaceutically acceptable salt thereof selected from the group consisting of the following compounds:

(1) (R)—N-(4-(4-methylpiperazin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(2) (S)—N-(4-(4-methylpiperazin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(3) (S)-6-(3-benzylisoxazolidin-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-4-amine;

(4) (R)—N-(3-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(5) (R)—N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(6) (R)—N-(4-(4-(4-cyclopropylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-amine;

(7) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-5-(1-methyl-1H-pyrazol-4-yl)-4-morpholinophenyl)pyrimidin-4-amine;

(8) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-5-(1-methyl-1H-pyrazol-4-yl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(9) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-5-(1-methyl-1H-pyrazol-5-yl)-4-morpholinophenyl)pyrimidin-4-amine;

(10) (R)-1′-(4-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-5-methoxy-2-(1-methyl-1H-pyrazol-4-yl)phenyl)-N,N-dimethyl-[1,4′-bipiperidin]-4-amine;

(11) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(3-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)-5-(methylsulfonyl)phenyl)pyrimidin-4-amine;

(12) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(3-(methylsulfonyl)-5-(4-morpholinopiperidin-1-yl)phenyl)pyrimidin-4-amine;

(13) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(3-(4-methylpiperazin-1-yl)-5-(methylsulfonyl)phenyl)pyrimidin-4-amine;

(14) (R)-2-(3-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-5-((4-methylpiperazin-1-yl)methyl)phenyl)-2-methylpropanenitrile;

(15) (R)-2-(3-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-5-(4-methylpiperazin-1-yl)phenyl)-2-methylpropanenitrile;

(16) (R)—N-(4-(4-methylpiperazin-1-yl)phenyl)-6-(3-(3-phenoxyphenyl)isoxazolidin-2-yl)pyrimidin-4-amine;

(17) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(18) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-4-amine;

(19) (R)—N 1 -(6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)-N 4 -(2-(dimethylamino)ethyl)-N 4 -methylbenzene-1,4-diamine;

(20) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-5-methyl-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(21) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(22) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)pyrimidin-4-amine;

(23) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)-3-(trifluoromethyl)phenyl)pyrimidin-4-amine;

(24) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)-3-(methylsulfonyl)phenyl)pyrimidin-4-amine;

(25) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(5-ethyl-2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(26) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(3-methoxy-4-(4-(4-methylpiperazin-1)-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(27) (R)—N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-(3-(trifluoromethyl)phenyl)isoxazolidin-2-yl)pyrimidin-4-amine;

(28) (R)-6-(3-(2-fluoro-3-(trifluoromethyl)phenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(29) (R)-6-(3-(3-fluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(30) (R)-6-(3-(2,5-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(31) (R)-6-(3-(3-chloro-4-fluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl) pyrimidin-4-amine;

(32) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(33) (R)-6-(3-(4-fluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(34) (R)-6-(3-(2,4-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(35) (R)—N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-(thiophen-2-yl)isoxazolidin-2-yl)pyrimidin-4-amine;

(36) (R)—N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-(naphthalen-1-yl)isoxazolidin-2-yl)pyrimidin-4-amine;

(37) (R)-6-(3-(3-ethynylphenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(38) (R)—N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-(6-methylpyridin-3-yl)isoxazolidin-2-yl)pyrimidin-4-amine;

(39) (R)-6-(3-(3-([1,2,4]triazolo[1,5-a]pyridin-7-yl)phenyl)isoxazolidin-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-4-amine;

(40) (R)-6-(3-(3-fluoro-5-thiomorpholinophenyl)isoxazolidin-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-4-amine;

(41) (R)—N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-(3-methoxyphenyl)isoxazolidin-2-yl)pyrimidin-4-amine;

(42) (R)-6-(3-methyl-3-phenylisoxazolidin-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-4-amine;

(43) isopropyl (R)-3-(2-(6-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)isoxazolidin-3-yl)benzoate;

(44) (R)—N-cyclohexyl-3-(2-(6-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)isoxazolidin-3-yl)benzamide;

(45) (R)-6-(3-(3′,5-difluoro-[1,1′-biphenyl]-3-yl)isoxazolidin-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-4-amine;

(46) (R)—N,N-dimethyl-7-(2-methyl-4-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)-7-azaspiro[3.5]nonan-2-amine;

(47) (R)—N,N-dimethyl-2-(2-methyl-4-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)-2-azaspiro[3.5]nonan-7-amine;

(48) (R)-3-(1-methylpiperidin-4-yl)-N-(6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)-1,2,3,4,4a,5-hexahydrobenzo[b]pyrazino[1,2-d][1,4]oxazin-8-amine;

(49) (6aR,8S)-8-(4-cyclopropylpiperazin-1-yl)-2-methoxy-N-(6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)-6,6a,7,8,9,10-hexahydrobenzo[b]pyrido[1,2-d][1,4]oxazin-3-amine;

(50) N-(4-(4-(5-ethylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)piperidin-1-yl)-2-methoxyphenyl)-6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(51) (R)—N-(2-methoxy-4-(4-((1-methylpiperidin-4-yl)amino)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(52) (R)—N-(2-methyl-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(53) (R)—N-(3-methyl-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(54) (R)—N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(55) (R)—N-(2-ethoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(56) N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)-2-(((R)-1,1,1-trifluoropropan-2-yl)oxy)phenyl)-6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(57) N-(2-methoxy-4-(4-((1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)piperidin-1-yl)phenyl)-6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(58) (R)—N-(2-methoxy-4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(59) N-(4-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-2-methoxyphenyl)-6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(60) (R)-1-(4-(1-(3-methoxy-4-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)piperidin-4-yl)piperazin-1-yl)ethan-1-one;

(61) (R)—N-(4-(4-(4-cyclopropyl-3,3-dimethylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(62) (R)—N-(2-methoxy-4-(4-(pyrrolidin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(63) (R)—N-(4-(4-(4-cyclopropylpiperazin-1-yl)-[1,4′-bipiperidin]-1′-yl)-2-methoxyphenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(64) (R)—N-(4-(2-(dimethylamino)ethoxy)-2-methoxyphenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(65) (R)—N-(4-((2-(dimethylamino)ethyl)thio)-2-methoxyphenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(66) (R)—N-(2-methoxy-4-thiomorpholinophenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(67) (R)—N-(2-methoxy-4-(4-methyl-1,4-diazepan-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(68) (R)—N-(4-(4-allylpiperazin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(69) N-(4-((R)-3-(dimethylamino)pyrrolidin-1-yl)phenyl)-6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(70) N-(4-((S)-2-((dimethylamino)methyl)pyrrolidin-1-yl)phenyl)-6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(71) (R)—N-(1-(1-(2-(dimethylamino)ethyl)piperidin-4-yl)-1H-pyrazol-4-yl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(72) (R)-(4-methylpiperazin-1-yl)(4-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)methanone;

(73) (R)-6-(3-phenylisoxazolidin-2-yl)-N-(3-(trifluoromethyl)phenyl)pyrimidin-4-amine;

(74) N-(5-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-2-fluoropyridin-3-yl)-6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(75) (R)-1-(4-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)pyrrolidin-2-one;

(76) (R)-2-methyl-5-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)isoindolin-1-one;

(77) (R)-6-(3-phenylisoxazolidin-2-yl)-N-(4-(piperazin-1-yl)phenyl)pyrimidin-4-amine;

(78) (R)—N-(6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine;

(79) (R)—N-(5-(4-(dimethylamino)piperidin-1-yl)pyridin-2-yl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(80) (R)—N-(8-(1-methyl-1H-pyrazol-5-yl)-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(81) (R)-1-cyclopropyl-4-(3-methoxy-4-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)-1,4-azaphosphinane 4-oxide;

(82) N-(4-((2R,6S)-2,6-dimethylmorpholino)phenyl)-6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(83) 6-((R)-3-phenylisoxazolidin-2-yl)-N—((R)-7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)pyrimidin-4-amine;

(84) (R)—N,N-dimethyl-1′-(4-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)-[1,4′-bipiperidin]-4-amine;

(88) (R)-7-(5-methoxy-2-methyl-4-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)-N,N-dimethyl-7-azaspiro[3.5]nonan-2-amine;

(89) (R)—N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-(naphthalen-2-yl)isoxazolidin-2-yl)pyrimidin-4-amine;

(90) (R)-6-(3-(3,4-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(91) (R)—N-(5-ethyl-2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-(4-fluorophenyl)isoxazolidin-2-yl)pyrimidin-4-amine;

(92) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(5-ethyl-2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(93) (R)-6-(3-(2,4-difluorophenyl)isoxazolidin-2-yl)-N-(5-ethyl-2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(94) (R)-6-(3-(2,5-difluorophenyl)isoxazolidin-2-yl)-N-(5-ethyl-2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(95) (R)-6-(3-(2,4-difluorophenyl)isoxazolidin-2-yl)-N-(3-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(96) (R)-6-(3-(4-fluorophenyl)isoxazolidin-2-yl)-N-(3-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(97) N-(4-(4-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)piperidin-1-yl)-2-methoxyphenyl)-6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(98) (R)—N-(4-(4-(diethylamino)piperidin-1-yl)-2-methoxyphenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(99) N-(2-methoxy-4-((R)-2-methyl-4-(1-methylpiperidin-4-yl)piperazin-1-yl)phenyl)-6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(100) isopropyl (R)-3-(2-(6-((2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)isoxazolidin-3-yl)benzoate;

(101) (R)—N-(2-methoxy-4-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(102) (R)—N-(3-methoxy-4-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(103) (R)-6-(3-(2,5-difluorophenyl)isoxazolidin-2-yl)-N-(3-methyl-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(104) (R)-6-(3-(2,4-difluorophenyl)isoxazolidin-2-yl)-N-(3-methyl-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(105) (R)-6-(3-(4-chloro-2-fluorophenyl)isoxazolidin-2-yl)-N-(3-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(106) (R)-6-(3-(2,5-difluorophenyl)isoxazolidin-2-yl)-N-(3-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(107) (R)—N-(3-methyl-4-(4-methylpiperazin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(108) (R)—N-(2-methyl-4-morpholinophenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(109) (R)—N-(5-ethyl-2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(110) (R)—N-(2-methoxy-4-morpholinophenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(111) (R)—N4-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-2,4-diamine;

(112) (R)—N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-4-(3-phenylisoxazolidin-2-yl)-1,3,5-triazin-2-amine;

(113) (R)-2-methoxy-N4-(1-methylpiperidin-4-yl)-N 1 -(6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)benzene-1,4-diamine;

(114) (R)—N-(2-methoxy-5-methyl-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(115) (R)-1′-(3-methoxy-4-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)-N,N-dimethyl-[1,4′-bipiperidin]-4-amine;

(116) N-(4-(4-((1R,4R)-5-ethyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)piperidin-1-yl)-2-methoxyphenyl)-6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(117) (R)—N-(3-ethyl-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(118) (R)—N-(4-(4-(4-ethylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(119) (R)—N-(4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(120) (R)—N-(2-methoxy-4-(4-morpholinopiperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(121) (R)-2-(4-(1-(2-methoxy-4-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)piperidin-4-yl)piperazin-1-yl)ethan-1-ol;

(122) (R)-1-(4-(4-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)piperazin-1-yl)ethan-1-one;

(123) (R)—N-(3,5-difluoro-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(124) (R)—N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(125) (R)-6-(3-(3-chloro-2-fluorophenyl)isoxazolidin-2-yl)-N-(3-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(126) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(3-methyl-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(127) (R)—N-(4-(4-(dimethylamino)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(128) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(3-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(129) (R)-6-(3-(4-chloro-3-fluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(130) (R)-6-(3-(3-chloro-2,4-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(131) (R)-6-(3-(3-(dimethylamino)phenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(132) (R)—N-(5-chloro-2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(133) (R)—N-(1-methyl-1H-pyrazol-4-yl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(134) tert-butyl (R)-7-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)-3,4-dihydroisoquinoline-2(1H)-carboxylate;

(135) (R)—N-(4-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(136) N-(4-(6-methyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)phenyl)-6-((R)-3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(137) (R)-3-(3-methoxy-4-((6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)oxazolidin-2-one;

(139) (R)—N-(4-(4-methylpiperazin-1-yl)-3-(2,2,2-trifluoroethoxy)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(140) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-(3-fluoro-4-(4-methylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)pyrimidin-4-amine;

(141) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)pyrimidin-4-amine;

(142) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(5-isopropyl-2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(143) (R)—N-(5-cyclopropyl-2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(144) (R)—N-(4-(4-methylpiperazin-1-yl)-2-(3-((methylsulfonyl)methyl)azetidin-1-yl)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(145) (R)-1-(5-((6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxy-2-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)ethan-1-one;

(146) (R,E)-1-(5-((6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-4-methoxy-2-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)ethan-1-one O-methyl oxime;

(147) (R)—N-(2-methoxy-5-(1-methyl-1H-pyrazol-4-yl)-6-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)pyridin-3-yl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(148) (R)-6-(3-(4-fluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-5-(1-methyl-1H-pyrazol-4-yl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(149) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-5-(1-methyl-1H-pyrazol-4-yl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(150) (R)—N-(6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)-5′-methoxyspiro[cyclopropane-1,3′-indoline]-6′-amine;

(151) (R)-6′-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-5′-methoxyspiro[cyclopropane-1,3′-indolin]-2′-one;

(152) (R)-1-(6-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-5-methoxy-1′-methylspiro[indolin-3,4′-piperidin]-1-yl)-2,2,2-trifluoroethan-1-one;

(153) (R)-6-((6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-7-methoxyspiro[benzo[b][1,4]oxazin-2,1′-cyclopropane]-3(4H)-one;

(154) (R)—N-(6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)-5-methoxy-1′-methylspiro[indolin-3,4′-piperidin]-6-amine;

(155) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(4-(1-methylpiperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)pyrimidin-4-amine;

(156) (R)—N-(6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)-3-methoxy-7-(4-methylpiperazin-1-yl)-9H-carbazol-2-amine;

(157) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(4-(piperidin-4-yl)-2,3-dihydrobenzofuran-7-yl)pyrimidin-4-amine;

(158) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(4-(1-methyl-1H-pyrazol-5-yl)-2,3-dihydrobenzofuran-7-yl)pyrimidin-4-amine;

(159) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(2,3-dihydrobenzofuran-7-yl)pyrimidin-4-amine;

(160) (R)-6-(3-(3,5-difluorophenyl)isoxazolidin-2-yl)-N-(4-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydrobenzofuran-7-yl)pyrimidin-4-amine;

(162) (R)—N-(5-(1-methyl-1H-pyrazol-4-yl)-4-(4-methylpiperazin-1-yl)-2,3-dihydrobenzofuran-7-yl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(164) (R)—N-(5-(1-methyl-1H-pyrazol-4-yl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)-2-(2,2,2-trifluoroethoxy)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(165) (R)—N-(5-(1-methyl-1H-pyrazol-4-yl)-4-(4-morpholinopiperidin-1-yl)-2-(2,2,2-trifluoroethoxy)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(166) (R)—N-(5-(1-methyl-1H-pyrazol-4-yl)-4-(4-methylpiperazin-1-yl)-2-(2,2,2-trifluoroethoxy)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(167) (R)—N-(5-(1-methyl-1H-pyrazol-4-yl)-4-morpholino-2-(2,2,2-trifluoroethoxy)phenyl)-6-(3-phenylisoxazolidin-2-yl)pyrimidin-4-amine;

(168) (S)-6-(3-(5-fluoropyridin-3-yl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(169) (R)-6-(3-(5-fluoropyridin-3-yl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(170) (R)-3-fluoro-5-(2-(6-((2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)isoxazolidin-3-yl)benzonitrile;

(171) (S)-3-fluoro-5-(2-(6-((2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)isoxazolidin-3-yl)benzonitrile;

(172) tert-butyl (R)-3-(4-((6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)isoxazolidin-2-carboxylate;

(173) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-((R)-2-methylisoxazolidin-3-yl)phenyl)pyrimidin-4-amine;

(174) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-((R)-isoxazolidin-3-yl)phenyl)pyrimidin-4-amine;

(175) tert-butyl (S)-3-(4-((6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)isoxazolidin-2-carboxylate;

(176) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-((S)-2-methylisoxazolidin-3-yl)phenyl)pyrimidin-4-amine;

(177) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-((S)-isoxazolidin-3-yl)phenyl)pyrimidin-4-amine;

(178) (R)-6-(3-(1-methyl-1H-pyrazol-4-yl)isoxazolidin-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-4-amine;

(179) (R)-6-(3-(furan-2-yl)isoxazolidin-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-4-amine;

(180) (R)-6-(3-(5-chloropyridin-3-yl)isoxazolidin-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-4-amine;

(181) (S)-6-(3-(5-chloropyridin-3-yl)isoxazolidin-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-4-amine;

(182) (R)-6-(3-(5-chloropyridin-3-yl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(183) (S)-6-(3-(5-chloropyridin-3-yl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(184) (R)-6-(3-(3-(difluoromethyl)phenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(185) (S)-6-(3-(3-(difluoromethyl)phenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(186) tert-butyl (R)-3-(3-((6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)isoxazolidin-2-carboxylate;

(187) tert-butyl (S)-3-(3-((6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)phenyl)isoxazolidin-2-carboxylate;

(188) (R)—N-(6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)cyclopropanecarboxamide;

(189) (R)—N-(6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)benzamide;

(190) (R)—N-(cyclopentylmethyl)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-amine;

(191) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-fluorobenzyl)pyrimidin-4-amine;

(192) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(1-(methylsulfonyl)piperidin-4-yl)pyrimidin-4-amine;

(193) (R)-6-((6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-5-methoxy-2-methylisoindolin-1-one;

(194) (R)-3-((6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-1H-indazol-6-carbonitrile;

(195) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-(9-(1-fluoro-2-methylpropan-2-yl)-3,9-diazaspiro[5.5]undecan-3-yl)-2-methoxy-5-(1-methyl-1H-pyrazol-4-yl)phenyl)pyrimidin-4-amine;

(196) (R)—N-(2,5-dichloro-4-(9-(1-fluoro-2-methylpropan-2-yl)-3,9-diazaspiro[5.5]undecan-3-yl)phenyl)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-amine;

(197) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(3-methyl-5-(3-((methylsulfonyl)methyl)azetidin-1-yl)-4-(4-morpholinopiperidin-1-yl)phenyl)pyrimidin-4-amine;

(198) (R)—N-(5-(3-chloro-1-methyl-1H-pyrazol-4-yl)-2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-amine;

(199) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-methylpiperazin-1-yl)-5-vinylphenyl)pyrimidin-4-amine;

(200) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(5-ethynyl-2-methoxy-4-(4-methylpiperazine-1-yl)phenyl)pyrimidin-4-amine;

(201) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(3-methoxy-6-(1-methyl-1H-pyrazol-4-yl)-5-(4-methylpiperazin-1-yl)pyridin-2-yl)pyrimidin-4-amine;

(202) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-5-(1-methyl-1H-pyrazol-4-yl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl)pyrimidin-4-amine;

(203) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(3-(1-methyl-1H-pyrazol-4-yl)-5-((2R,3S)-2-methyl-3-((methylsulfonyl)methyl)azetidin-1-yl)-4-morpholinophenyl)pyrimidin-4-amine;

(204) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N4-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-N2-methylpyrimidin-2,4-diamine;

(205) (R)-4-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyridin-2-amine;

(206) (R)—N-(4-(4-(4-allylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-amine;

(207) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-(4-ethylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)pyrimidin-4-amine;

(208) (R)—N-(4-(4-(4-cyclobutylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-amine;

(209) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-(oxetan-3-yl)piperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(210) (R)—N-(4-(4-(4-(cyclopropylmethyl)piperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-amine;

(211) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(212) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-((R)-3-(dimethylamino)pyrrolidin-1-yl)piperidin-1-yl)-2-methoxyphenyl)pyrimidin-4-amine;

(213) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-((R)-3,4-dimethylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)pyrimidin-4-amine;

(214) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-((S)-3,4-dimethylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)pyrimidin-4-amine;

(215) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-((3S,5R)-4-ethyl-3,5-dimethylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)pyrimidin-4-amine;

(216) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-((S)-2,4-dimethylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)pyrimidin-4-amine;

(217) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-((R)-2,4-dimethylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)pyrimidin-4-amine;

(218) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(3-(4-methylpiperazin-1-yl)azetidin-1-yl)phenyl)pyrimidin-4-amine;

(219) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-(6-ethyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)piperidin-1-yl)-2-methoxyphenyl)pyrimidin-4-amine;

(220) 6-((R)-3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-(3-ethyl-3,6-diazabicyclo[3.1.1]heptan-6-yl)piperidin-1-yl)-2-methoxyphenyl)pyrimidin-4-amine;

(221) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-methyl-1,4)-diazepan-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine;

(222) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(4-(4-(4-isopropylpiperazin-1-yl)piperidin-1-yl)-2-methoxyphenyl)pyrimidin-4-amine;

(223) (R)-1-(1-(4-((6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-3-methoxyphenyl)piperidin-4-yl)-4-methylpiperazin-2-one;

(224) (R)-4-(1-(4-((6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)pyrimidin-4-yl)amino)-3-methoxyphenyl)piperidin-4-yl)-1-methylpiperazin-2-one;

(225) (R)-1-methyl-5-(2-(6-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)isoxazolidin-3-yl)pyridin-2(1H)-one;

(226) (R)-5-(2-(6-((2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)isoxazolidin-3-yl)-1-methylpyridin-2(1H)-one;

(227) (S)-1-methyl-5-(2-(6-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)isoxazolidin-3-yl)pyridin-2(1H)-one;

(228) (S)-5-(2-(6-((2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)isoxazolidin-3-yl)-1-methylpyridin-2(1H)-one;

(229) N-(4-(4-methylpiperazin-1-yl)phenyl)-6-(3-phenylbenzo[d]isoxazol-2(3H)-yl)pyrimidin-4-amine;

(230) N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(3-phenylbenzo[d]isoxazol-2(3H)-yl)pyrimidin-4-amine;

(231) (S)—N-(4-(4-methylpiperazin-1-yl)phenyl)-6-(7-phenyl-5-oxa-6-azaspiro[2.4]heptan-6-yl)pyrimidin-4-amine;

(232) (R)—N-(4-(4-methylpiperazin-1-yl)phenyl)-6-(7-phenyl-5-oxa-6-azaspiro[2.4]heptan-6-yl)pyrimidin-4-amine;

(233) (S)—N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(7-phenyl-5-oxa-6-azaspiro[2.4]heptan-6-yl)pyrimidin-4-amine;

(234) (R)—N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)-6-(7-phenyl-5-oxa-6-azaspiro[2.4]heptan-6-yl)pyrimidin-4-amine;

(235) (R)-6-(3-isopropylisoxazolidin-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-4-amine;

(236) (S)-6-(3-isopropylisoxazolidin-2-yl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-4-amine; and

(237) (R)-6-(3-(2,3-difluorophenyl)isoxazolidin-2-yl)-N-(2-methoxy-4-(4-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-4-amine.