Pyrimidine derivatives as kinase modulators and method of use
View Patent ↗The invention provides compounds and methods for inhibition of kinases, more specifically IGF 1 R kinases. The invention also provides compounds and methods for inhibition of wildtype Abl. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinase receptor signal transduction pathways related to the changes in cellular activities as mentioned above, and the invention includes compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein, V is NR 1 R 1a , or O—R 1 , wherein X is H, halo, C 1 -C 6 alkyl, NO 2 , mono-, di-, or tri-halo substituted methyl, NR 13 R, 14 . C(O)O—C 1 -C 6 alkyl, or N(R 13 )—C(O)—C 1 -C 6 alkyl; Y is H, halo, OH, C 1 -C 6 alkyl, C 0 -C 6 alkyl-NR, 15 R 16 , NR 15 R, 6 , C 1 -C 6 alkoxy, —N(R 13 )—(CH 2 ) n- NR 15 R 16 , —C(O)O—C 1 -C 6 alkyl, —O—(CH 2 ) n —NR 15 R 16 , —C(O)—C 1 -C 6 alkyl, —C 0 -C 6 -alkyl-R 21 , —O—R 21 , —C(O)—R 21 , —O—(CH 2 ) n —R 21 , —C(O)—NR 13 R 14 , —C(O)—N(R 13 )-aryl, —C(O)—N(R 13 )(CH 2 ) n —NR 15 R 16 , —C(O)—N(R 13 )—(CH 2 ) n -aryl —C(O)—N(R 13 )—(CH 2 ) n -heterocyclyl; or X and Y together with the atoms to which they are attached form a 4-7 membered heterocyclyl or heteroaryl group containing one or two heteroatoms independently selected from O, N, and S. Z is H, NR 2 R 3 , —S—R 2a , or —O—R 2a
1. A compound of Formula VI,
or a pharmaceutically acceptable salt thereof, wherein,
m is 1 or 2 or 3;
R 5 is C 1 -C 6 alkyl, or —C 0 -C 6 alkyl-R 21 ;
X is H, or halo;
Y is —C 0 -C 6 -alkyl-R 21 ;
R 6 is —C 0 -C 6 -alkyl-R 21 or C 1 -C 6 alkyl;
R 21 is a heterocyclyl group, which may be aromatic, having 3-15 ring members and from 1-5 hetero atoms where the hetero atoms are selected from nitrogen, phosphorus, oxygen and sulfur, aryl, or C 3 -C 7 cycloalkyl, and wherein aryl, C 3 -C 7 cycloalkyl, and heterocyclyl are optionally substituted with one or two moieties independently selected from halo, —S(O) 2 —C 1 alkyl, —C(O)—C 1 alkyl, —C(O)—H, —C 0 -C 1 alkyl-aryl, C 1 -C 6 alkyl and NR 13 R 14 wherein R 13 and R 14 are independently H or C 1 -C 6 alkyl.
2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y is heterocyclyl optionally substituted with C 1 -C 3 alkyl, X is H or halo, R 5 is C 3 -C 4 cycloalkyl and R 6 is C 1 -C 4 alkyl.
3. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof, wherein Y is heterocyclyl optionally substituted with methyl, ethyl, propyl or isopropyl, X is H, R 5 is cyclopropyl and R 6 is methyl, ethyl, propyl or isopropyl.
4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, selected from the following:
Entry
Structure
Name
8
12
43
46
183
496
497
499
503
505
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511
519
520
557
561
575
N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-N 4 -[5-(1- methylethyl)-1H-pyrazol-3-yl]- 6-[(3S)-3-methylpiperazin-1- yl]pyrimidine-2,4-diamine
591
N 4- [5-(1-methylethyl)-1H- pyrazol-3-yl]-6-[(3S)-3- methylpiperazin-1-yl]-N 2 -[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
601
N 4 -(3-cyclopropyl-1H-pyrazol- 5-yl)-N 2 -[(3-methylisoxazol-5- yl)methyl]-6-morpholin-4- ylpyrimidine-2,4-diamine
602
N 4 -(3-cyclopropyl-1H-pyrazol- 5-yl)-N 2 -[(3-methylisoxazol-5- yl)methyl]-6-(4- methylpiperazin-1- yl)pyrimidine-2,4-diamine
604
N 4 -(3-cyclopropyl-1H-pyrazol- 5-yl)-N 2 -{[3-(4- fluorophenyl)isoxazol-5- yl]methyl}-6-morpholin-4- ylpyrimidine-2,4-diamine
605
N 4 -(3-cyclopropyl-1H-pyrazol- 5-yl)-N 2 -{[3-(4- fluorophenyl)isoxazol-5- yl]methyl}-6-(4- methylpiperazin-1- yl)pyrimidine-2,4-diamine
607
N 2 -{[3-(4- fluorophenyl)isoxazol-5- yl]methyl}-N 4 -[3-(1- methylethyl)-1H-pyrazol-5-yl]- 6-morpholin-4-ylpyrimidine- 2,4-diamine
608
N 2 -{[3-(4- fluorophenyl)isoxazol-5- yl]methyl}-N 4 -[3-(1- methylethyl)-1H-pyrazol-5-yl]- 6-(4-methylpiperazin-1- yl)pyrimidine-2,4-diamine
611
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-6-(4-methylpiperazin-1- yl)-N 2 -[(3-pyridin-2-ylisoxazol- 5-yl)methyl]pyrimidine-2,4- diamine
612
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-6-morpholin-4-yl-N 2 -[(3- pyridin-2-ylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
613
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-piperazin-1- ylpyrimidine-2,4-diamine
614
6-(4-acetylpiperazin-1-yl)-N 4 - (5-cyclopropyl-1H-pyrazol-3- yl)-N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4- diamine
615
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[4- (methylsulfonyl)piperazin-1- yl]pyrimidine-2,4-diamine
616
4-{6-[(5-cyclopropyl-1H- pyrazol-3-yl)amino]-2-({[3-(1- methylethyl)isoxazol-5- yl]methyl}amino)pyrimidin-4- yl}piperazine-1-carbaldehyde
617
N 4 -(3-methyl-1H-pyrazol-5- yl)-6-morpholin-4-yl-N 2 -[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
618
6-(4-methylpiperazin-1-yl)-N 4 - (3-methyl-1H-pyrazol-5-yl)- N 2 -[(3-phenylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
624
5-chloro-N 4 -(3-cyclopropyl- 1H-pyrazol-5-yl)-6-morpholin- 4-yl-N 2 -[(3-phenylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
625
5-chloro-N 4 -(3-cyclopropyl- 1H-pyrazol-5-yl)-6-(4- methylpiperazin-1-yl)-N 2 -[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
626
N 2 -[(3-methylisoxazol-5- yl)methyl]-6-(4- methylpiperazin-1-yl)-N 4 -(3- methyl-1H-pyrazol-5- yl)pyrimidine-2,4-diamine
627
N 2 -[(3-methylisoxazol-5- yl)methyl]-N 4 -(3-methyl-1H- pyrazol-5-yl)-6-morpholin-4- ylpyrimidine-2,4-diamine
628
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-6-(4-methylpiperazin-1- yl)-N 2 -[(3-pyrimidin-4- ylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
629
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-N 2 -[(3-furan-3- ylisoxazol-5-yl)methyl]-6-(4- methylpiperazin-1- yl)pyrimidine-2,4-diamine
631
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-6-(5-methyl-2,5- diazabicyclo[2.2.1]hept-2-yl)- N 2 -[(3-methylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
632
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-6-(5-methyl-2,5- diazabicyclo[2.2.1]hept-2-yl)- N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4- diamine
635
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-N 2 -[(3-methylisoxazol-5- yl)methyl]-6-[(1R,4R)-5- (phenylmethyl)-2,5- diazabicyclo[2.2.1]hept-2- yl]pyrimidine-2,4-diamine
636
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(1R,4R)-5- (phenylmethyl)-2,5- diazabicyclo[2.2.1]hept-2- yl]pyrimidine-2,4-diamine
637
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-6-morpholin-4-yl-N 2 -[(3- pyrimidin-4-ylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
640
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-6-(4-methylpiperazin-1- yl)-N 2 -{[3-(2-thienyl)isoxazol- 5-yl]methyl}pyrimidine-2,4- diamine
642
N 4 -(3-cyclopropyl-1H-pyrazol- 5-yl)-6-(4-methylpiperazin-1- yl)-N 2 -[(3-pyrimidin-5- ylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
643
N 4 -(3-cyclopropyl-1H-pyrazol- 5-yl)-6-morpholin-4-yl-N 2 -[(3- pyrimidin-5-ylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
648
N 4 -(5-cyclopropyl-1H-pyrazol- 3-yl)-6-(4-methylpiperazin-1- yl)-N 2 -{[3-(1,3-thiazol-2- yl)isoxazol-5- yl]methyl}pyrimidine-2,4- diamine
655
N 4 -(3-cyclopropyl-1H-pyrazol- 5-yl)-N 2 -[(3-ethylisoxazol-5- yl)methyl]-6-(4- methylpiperazin-1- yl)pyrimidine-2,4-diamine
656
N 4 -(3-cyclopropyl-1H-pyrazol- 5-yl)-N 2 -[(3-ethylisoxazol-5- yl)methyl]-6-morpholin-4- ylpyrimidine-2,4-diamine
660
N 2 {[3-(2-aminopyrimidin-4- yl)isoxazol-5-yl]methyl}-N 4 -(3- cyclopropyl-1H-pyrazol-5-yl)- 6-(4-methylpiperazin-1- yl)pyrimidine-2,4-diamine
661
N 4 -(3-cyclopropyl-1H-pyrazol- 5-yl)-6-(4-ethylpiperazin-1- yl)-N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4- diamine.
5. A compound or a pharmaceutically acceptable salt thereof, selected from
Entry
Structure
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495
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531
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541
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566
567
568
569
570
571
572
573
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 6 -[3- (diethylamino)propyl]-N 2 - {[3-(1-methylethyl)isoxazol- 5-yl]methyl}pyrimidine- 2,4,6-triamine
574
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 6 -[2- (diethylamino)ethyl]-N 2 -{[3- (1-methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4,6- triamine
576
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-6-{[2- (dimethylamino)ethyl]oxy}- N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4- diamine
577
N 4 -[3-(1-methylethyl)-1H- pyrazol-5-yl]-6-[(1- methylpyrrolidin-3-yl)oxy]- N 2 -[(3-phenylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
578
N 4 -(3-cyclopropyl-1H- pyrazol-5-yl)-N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(1- methylpyrrolidin-3- yl)oxy]pyrimidine-2,4- diamine
579
N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-N 4 -[3-(1- methylethyl)-1H-pyrazol-5- yl]-6-[(1-methylpyrrolidin-3- yl)oxy]pyrimidine-2,4- diamine
580
N 4 -[2-(diethylamino)ethyl]- N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-N 6 -[5-(1- methylethyl)-1H-pyrazol-3- yl]pyrimidine-2,4,6-triamine
581
N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-N 4 -[5-(1- methylethyl)-1H-pyrazol-3- yl]pyrimidine-2,4-diamine
582
N 4 -[5-(1-methylethyl)-1H- pyrazol-3-yl]-6-[(1- methylpiperidin-3-yl)oxy]- N 2 -[(3-phenylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
583
N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-N 4 -[5-(1- methylethyl)-1H-pyrazol-3- yl]-6-[(1-methylpiperidin-3- yl)oxy]pyrimidine-2,4- diamine
584
N-(5- cyclopropyl-1H- pyrazol-3-yl)-6-methyl-2- {[(3-phenylisoxazol-5- yl)methyl]oxy}pyrimidin-4- amine
585
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-6-methyl-N 2 - [(4-phenyl-1H-imidazol-2- yl)methyl]pyrimidine-2,4- diamine
586
6-{[2- (dimethylamino)ethyl]oxy}- N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-N 4 -[5-(1- methylethyl)-1H-pyrazol-3- yl]pyrimidine-2,4-diamine
587
N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-N 4 -[5-(1- methylethyl)-1H-pyrazol-3- yl]-6-[(2-morpholin-4- ylethyl)oxy]pyrimidine-2,4- diamine
588
N 4 -[5-(1-methylethyl)-1H- pyrazol-3-yl]-6-[(2- morpholin-4-ylethyl)oxy]-N 2 - [(3-phenylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
589
N 4 -[3-(1-methylethyl)-1H- pyrazol-5-yl]-N 2 -[(3- phenylisoxazol-5-yl)methyl]- 6-[(2-piperidin-1- ylethyl)oxy]pyrimidine-2,4- diamine
590
N 4 -[3-(diethylamino)propyl]- N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-N 6 -[5-(1- methylethyl)-1H-pyrazol-3- yl]pyrimidine-2,4,6-triamine
592
N 4 -[2-(diethylamino)ethyl]- N 6 -[5-(1-methylethyl)-1H- pyrazol-3-yl]-N 2 -[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4,6- triamine
593
N 4 -[5-(1-methylethyl)-1H- pyrazol-3-yl]-6-[(1- methylpiperidin-4-yl)oxy]- N 2 -[(3-phenylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
594
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(2-morpholin- 4-ylethyl)oxy]pyrimidine-2,4- diamine
595
N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-N 4 -[3-(1- methylethyl)-1H-pyrazol-5- yl]-6-[(2-piperidin-1- ylethyl)oxy]pyrimidine-2,4- diamine
596
N 4 -(3-cyclopropyl-1H- pyrazol-5-yl)-6-[3- (diethylamino)propyl]-N 2 -[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
597
N 4 -(3-cyclopropyl-1H- pyrazol-5-yl)-N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(2-piperidin-1- ylethyl)oxy]pyrimidine-2,4- diamine
598
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(1- methylpiperidin-3- yl)oxy]pyrimidine-2,4- diamine
599
N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-N 4 -[3-(1- methylethyl)-1H-pyrazol-5- yl]-6-[(1-methylpiperidin-4- yl)oxy]pyrimidine-2,4- diamine
600
N 4 -(3-cyclopropyl-1H- pyrazol-5-yl)-6-methyl-N 2 - [(3-methylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
603
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(1- methylpiperidin-4- yl)oxy]pyrimidine-2,4- diamine
606
N 4 -(3-cyclopropyl-1H- pyrazol-5-yl)-N 2 -{[3-(4- fluorophenyl)isoxazol-5- yl]methyl}-6-[(2-morpholin- 4-ylethyl)oxy]pyrimidine-2,4- diamine
609
N 2 -{[3-(4- fluorophenyl)isoxazol-5- yl]methyl}-N 4 -[3-(1- methylethyl)-1H-pyrazol-5- yl]-6-[(2-morpholin-4- ylethyl)oxy]pyrimidine-2,4- diamine
610
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-6-methyl-N 2 - [(3-pyridin-3-ylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
619
N 4 -(3-methyl-1H-pyrazol-5- yl)-6-[(2-morpholin-4- ylethyl)oxy]-N 2 -[(3- phenylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
620
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-6-methyl-N 2 - [(3-pyridin-4-ylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
621
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 2 -{[3-(3,4- difluorophenyl)isoxazol-5- yl]methyl}-6- methylpyrimidine-2,4- diamine
622
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 2 -{[3-(2,4- difluorophenyl)isoxazol-5- yl]methyl}-6- methylpyrimidine-2,4- diamine
623
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-6-methyl-N 2 - [(3-pyrazin-2-ylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
630
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 6 -(8-methyl-8- azabicyclo[3.2.1]oct-3-yl)-N 2 - [(3-methylisoxazol-5- yl)methyl]pyrimidine-2,4,6- triamine
633
N 4 -bicyclo[2.2.1]hept-2-yl- N 6 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}pyrimidine-2,4,6- triamine
634
N 4 -bicyclo[2.2.1]hept-2-yl- N 6 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 2 -[(3- methylisoxazol-5- yl)methyl]pyrimidine-2,4,6- triamine
638
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-6-{[2- (dimethylamino)ethyl]oxy}- N 2 -[(3-pyrimidin-4- ylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
639
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 2 -{[3-(5- fluoropyridin-2-yl)isoxazol-5- yl]methyl}-6- methylpyrimidine-2,4- diamine
641
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-6-{[2- (dimethylamino)ethyl]oxy}- N 2 -[(3-pyridin-2-ylisoxazol- 5-yl)methyl]pyrimidine-2,4- diamine
644
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-6-{[2- (diethylamino)ethyl]oxy}-N 2 - {[3-(1-methylethyl)isoxazol- 5-yl]methyl}pyrimidine-2,4- diamine
645
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 2 -{[3-(1- methylethyl)isoxazol-5- yl]methyl}-6-[(2-pyrrolidin-1- ylethyl)oxy]pyrimidine-2,4- diamine
646
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-6-{[2- (diethylamino)ethyl]oxy}-N 2 - [(3-methylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
647
N 4 -(5-cyclopropyl-1H- pyrazol-3-yl)-N 2 -[(3- methylisoxazol-5-yl)methyl]- 6-[(2-pyrrolidin-1- ylethyl)oxy]pyrimidine-2,4- diamine
649
N 4 -(3-cyclopropyl-1H- pyrazol-5-yl)-6-[2- (dimethylamino)ethoxy]-N 2 - [(3-methylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
650
6-{[2- (dimethylamino)ethyl]oxy}- N 2 -[(3-methylisoxazol-5- yl)methyl]-N 4 -(3-methyl-1H- pyrazol-5-yl)pyrimidine-2,4- diamine
651
6-{[2- (diethylamino)ethyl]oxy}-N 2 - [(3-methylisoxazol-5- yl)methyl]-N 4 -(3-methyl-1H- pyrazol-5-yl)pyrimidine-2,4- diamine
652
N 2 -[(3-methylisoxazol-5- yl)methyl]-N 4 -(3-methyl-1H- pyrazol-5-yl)-6-[(2- pyrrolidin-1- ylethyl)oxy]pyrimidine-2,4- diamine
653
N 4 -(3-cyclopropyl-1H- pyrazol-5-yl)-6-methyl-N 2 -[2- (3-phenylisoxazol-5- yl)ethyl]pyrimidine-2,4- diamine
654
N 4 -(3-cyclopropyl-1H- pyrazol-5-yl)-6-methyl-N 2 -[1- (3-phenylisoxazol-5- yl)ethyl]pyrimidine-2,4- diamine
657
N 4 -(3-cyclopropyl-1H- pyrazol-5-yl)-6-{[2- (dimethylamino)ethyl]oxy}- N 2 -[(3-ethylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
658
N 4 -(3-cyclopropyl-1H- pyrazol-5-yl)-6-{[2- (diethylamino)ethyl]oxy}-N 2 - [(3-ethylisoxazol-5- yl)methyl]pyrimidine-2,4- diamine
659
N 4 -(3-cyclopropyl-1H- pyrazol-5-yl)-N 2 -[(3- ethylisoxazol-5-yl)methyl]-6- [(2-pyrrolidin-1- ylethyl)oxy]pyrimidine-2,4- diamine
662
2-(2-{6-[(3-cyclopropyl-1H- pyrazol-5-yl)amino]-2-({[3- (1-methylethyl)isoxazol-5- yl]methyl}amino)pyrimidin- 4-yl}piperidin-4-yl)ethanol
663
2-(4-{6-[(3-cyclopropyl-1H- pyrazol-5-yl)amino]-2-({[3- (1-methylethyl)isoxazol-5- yl]methyl}amino)pyrimidin- 4-yl}piperazin-1-yl)ethanol.
6. The compound of claim 4 depicted below
or a pharmaceutically acceptable salt thereof.
7. A pharmaceutical composition comprising a compound according to claim 1 or 6 and a pharmaceutically acceptable carrier, excipient, or diluent.