Kinase inhibitors and methods of their use
New compounds, compositions and methods of inhibition of Provirus Integration of Maloney Kinase (PIM kinase) activity associated with tumorigenesis in a human or animal subject are provided. In certain embodiments, the compounds and compositions are effective to inhibit the activity of at least one PIM kinase. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a serine/threonine kinase- or receptor tyrosine kinase-mediated disorder, such as cancer.
1. A compound of Formula II, or a pharmaceutically acceptable salt thereof,
wherein:
Y is cyclohexyl, substituted with one to three substituents selected from hydroxyl, amino, C 1-4 alkyl and C 1-4 halo alkyl;
R 1 is hydrogen, —NH 2 , or halo;
R 12 independently at each occurrence is selected from hydrogen and halo; and
R 5 is cyclohexyl or phenyl, where each R 5 is independently substituted with up to three substituents selected from halo, hydroxyl, C 1-4 alkyl, and OC 1-4 alkyl.
2. A compound of claim 1 , wherein Y is substituted with one to three substituents selected from methyl, hydroxyl, amino, and CF 3 .
3. A compound of claim 1 , wherein R 1 is hydrogen, amino, or fluoro.
4. A compound of claim 1 , wherein R 5 is phenyl.
5. A compound of claim 4 wherein R 5 is substituted phenyl that is substituted with up to three substituents selected from halo, hydroxyl, C 1-4 alkoxy, and C 1-4 alkyl.
6. A compound of claim 4 wherein Y is substituted with one to three substituents selected from methyl, hydroxyl, amino, and CF 3 ; R 1 is hydrogen; and R 5 is phenyl substituted with up to three substituents selected from fluoro, hydroxyl, methyl, ethyl, methoxy, and propoxy.
7. A compound of claim 6 wherein R 5 is 2,6-difluorophenyl.
8. A compound of claim 1 , selected from the group consisting of
N-(4-((3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide;
3-amino-N-(4-((1R,3R,4S,5S)-3-amino-4-hydroxy-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)picolinamide;
3-amino-N-(4-((1R,3S)-3-aminocyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide; and
N-(4-((3S)-3-aminocyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide, or a stereoisomer or pharmaceutically acceptable salt thereof.
9. A pharmaceutical composition comprising a compound of claim 1 or claim 8 and a pharmaceutically acceptable carrier.
10. A compound selected from the group consisting of:
99
N-(4-((1R,3S)-3-aminocyclohexyl)pyridin-3- yl)-6-(2,6-difluorophenyl)-5- fluoropicolinamide
70
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
51
3-amino-N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
63
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)picolinamide
94
3-amino-N-(4-(3-amino-4-hydroxy-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)picolinamide
100
3-amino-N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
133
3-amino-N-(4-(3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
and the pharmaceutically acceptable salts thereof.
11. The compound of claim 10 , which is of the formula:
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 10 , which is of the formula:
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 10 , which is of the formula:
or a pharmaceutically acceptable salt thereof.
14. The compound of claim 10 , which is of the formula:
or a pharmaceutically acceptable salt thereof.
15. The compound of claim 10 , which is of the formula:
or a pharmaceutically acceptable salt thereof.
16. The compound of claim 10 , which is of the formula:
or a pharmaceutically acceptable salt thereof.
17. The compound of claim 10 , which is of the formula:
or a pharmaceutically acceptable salt thereof.
18. The compound of claim 3 , wherein R 1 is amino.
19. A compound of Formula II selected from the group consisting of:
1
6-(2,6-difluorophenyl)-5-fluoro-N-(4- ((1R,3S,5S)-3-hydroxy-5- methylcyclohexyl)pyridin-3- yl)picolinamide
4
N-(4-((1R,3R,4R,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(2,6-difluoro-4- hydroxyphenyl)-5-fluoropicolinamide
5
N-(4-((1R,3R,4R,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-5-fluoro-6-(2-fluoro-5- hydroxyphenyl)picolinamide
6
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2- fluoro-4-hydroxyphenyl)picolinamide
7
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2- fluoro-5-hydroxyphenyl)picolinamide
8
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2,6- difluoro-4- hydroxyphenyl)picolinamide
9
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-5- fluoro-6-(2-fluoro-4- hydroxyphenyl)picolinamide
10
N-(4-((1R,5R)-5-amino-3,3- dimethylcyclohexyl)pyridin-3-yl)-5- fluoro-6-(2-fluoro-4- hydroxyphenyl)picolinamide
11
N-(4-((1R,5R)-5-amino-3,3- dimethylcyclohexyl)pyridin-3-yl)-6- (2,6-difluoro-3-methylphenyl)-5- fluoropicolinamide
12
N-(4-((1R,5R)-5-amino-3,3- dimethylcyclohexyl)pyridin-3-yl)-6- (2,6-difluoro-3- methylphenyl)picolinamide
14
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-5- fluoro-6-(2,3,5- trifluorophenyl)picolinamide
15
N-(4-((1R,3R,4R,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(3-ethyl-2,6- difluorophenyl)picolinamide
17
N-(4-((1R,3R,4S,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(3-ethyl-2,6- difluorophenyl)picolinamide
18
N-(4-((1R,3R,4S)-3-amino-4- hydroxycyclohexyl)pyridin-3-yl)-6-(3- ethyl-2,6-difluorophenyl)picolinamide
19
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(3- ethyl-2,6-difluorophenyl)picolinamide
20
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2,6- difluoro-3-methylphenyl)-5- fluoropicolinamide
21
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(3- ethyl-2,6-difluorophenyl)picolinamide
27
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluoro-3-methylphenyl)-5- fluoropicolinamide
28
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2,6- difluoro-3-methylphenyl)picolinamide
29
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluoro-3-methylphenyl)picolinamide
30
N-(4-((1R,3R,4R,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(2,6-difluoro-3- methylphenyl)picolinamide
31
N-(4-((1R,3R,4S,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(2,6-difluoro-3- methylphenyl)picolinamide
32
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2,6- difluoro-4-hydroxyphenyl)-5- fluoropicolinamide
33
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-5- fluoro-6-(2-fluoro-5- hydroxyphenyl)picolinamide
34
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-3- fluoro-6-(2-fluoro-5- hydroxyphenyl)picolinamide
35
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2- fluoro-5-hydroxyphenyl)picolinamide
36
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluoro-4- hydroxyphenyl)picolinamide
37
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2- fluoro-4-hydroxyphenyl)picolinamide
38
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-5- fluoro-6-(2-fluoro-4- hydroxyphenyl)picolinamide
39
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-3- fluoro-6-(2-fluoro-4- hydroxyphenyl)picolinamide
40
N-(4-((1R,3R,4S,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(2,6-difluoro-3-methylphenyl)- 5-fluoropicolinamide
41
N-(4-((1R,3R,4S)-3-amino-4- hydroxycyclohexyl)pyridin-3-yl)-6- (2,6-difluoro-3- methylphenyl)picolinamide
42
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluoro-4-hydroxyphenyl)-3- fluoropicolinamide
43
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-3- fluoro-6-(2-fluoro-5- hydroxyphenyl)picolinamide
44
N-(4-((1R,3R,4R,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(2,6-difluoro-3-methylphenyl)- 5-fluoropicolinamide
45
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-5- fluoro-6-(2-fluoro-5- methoxyphenyl)picolinamide
46
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-5- fluoro-6-(2-fluoro-5- hydroxyphenyl)picolinamide
47
N-(4-((1R,3R,4R,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(2,6-difluoro-3- methoxyphenyl)-5-fluoropicolinamide
48
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6- (2,3,5-trifluorophenyl)picolinamide
49
N-(4-((1R,5R)-5-amino-3,3- dimethylcyclohexyl)pyridin-3-yl)-6- (2,6-difluorophenyl)-5- fluoropicolinamide
50
N-(4-((1R,3R,4R,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(2,6-difluorophenyl)-5- fluoropicolinamide
51
3-amino-N-(4-((1R,3S,5S)-3-amino- 5-methylcyclohexyl)pyridin-3-yl)-6- (2,6-difluorophenyl)-5- fluoropicolinamide
52
N-(4-((1S,3S,4S,5R)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(2,6- difluorophenyl)picolinamide
53
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-5- fluoro-6-((1s,4s)-4- hydroxycyclohexyl)picolinamide
54
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-5- fluoro-6-((1s,4s)-4- hydroxycyclohexyl)picolinamide
55
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-5- fluoro-6-((1r,4r)-4- hydroxycyclohexyl)picolinamide
56
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-5- fluoro-6-((1r,4r)-4- hydroxycyclohexyl)picolinamide
57
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-5- fluoro-6-(2-fluorophenyl)picolinamide
58
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2- fluoro-5-methylphenyl)picolinamide
59
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-5- fluoro-6-(2-fluoro-5- methylphenyl)picolinamide
60
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,3- difluorophenyl)-5-fluoropicolinamide
61
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,5- difluorophenyl)-5-fluoropicolinamide
62
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2- fluorophenyl)picolinamide
63
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)picolinamide
64
N-(4-((1R,3R,4S)-3-amino-4- hydroxycyclohexyl)pyridin-3-yl)-5- fluoro-6-(2-fluoro-5- propoxyphenyl)picolinamide
65
3-amino-N-(4-((1R,3R,4S)-3-amino- 4-hydroxycyclohexyl)pyridin-3-yl)-6- (2,6-difluorophenyl)-5- fluoropicolinamide
66
3-amino-N-(4-((1R,3R,4S)-3-amino- 4-hydroxycyclohexyl)pyridin-3-yl)-5- fluoro-6-(2-fluorophenyl)picolinamide
67
3-amino-N-(4-((1R,3R,4S)-3-amino- 4-hydroxycyclohexyl)pyridin-3-yl)-5- fluoro-6-(2-fluoro-5- propoxyphenyl)picolinamide
68
3-amino-N-(4-((1R,3R,4S)-3-amino- 4-hydroxycyclohexyl)pyridin-3-yl)-6- (2-fluoro-5- propoxyphenyl)picolinamide
69
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-3-fluoropicolinamide
70
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
71
N-(4-((1S,3R,5R)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-3-fluoropicolinamide
72
N-(4-((1S,3R,5R)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
73
N-(4-((1R,3R,4S,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-5-fluoro-6-(2-fluoro-5- methylphenyl)picolinamide
74
N-(4-((1R,3R,4S,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(2-fluoro-5- methylphenyl)picolinamide
75
N-(4-((1R,3R,4S,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-5-fluoro-6-(2- fluorophenyl)picolinamide
76
N-(4-((1R,3R,4S,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(2,6- difluorophenyl)picolinamide
77
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,4- difluorophenyl)-5-fluoropicolinamide
78
N-(4-((1R,3R,4S)-3-amino-4- hydroxycyclohexyl)pyridin-3-yl)-6- (2,6-difluorophenyl)picolinamide
79
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2,3- difluorophenyl)-5-fluoropicolinamide
80
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-3-fluoropicolinamide
81
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2,5- difluorophenyl)-5-fluoropicolinamide
82
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2,4- difluorophenyl)-5-fluoropicolinamide
83
N-(4-((1R,3R,4S)-3-amino-4- hydroxycyclohexyl)pyridin-3-yl)-6-(2- fluorophenyl)picolinamide
84
N-(4-((1R,3R,4S)-3-amino-4- hydroxycyclohexyl)pyridin-3-yl)-6-(2- fluoro-5-propoxyphenyl)picolinamide
85
N-(4-((1R,3R,4S,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(2,6-difluorophenyl)-5- fluoropicolinamide
86
N-(4-((1R,3R,4S,5S)-3-amino-4- hydroxy-5-methylcyclohexyl)pyridin- 3-yl)-6-(2,6-difluorophenyl)-5- fluoropicolinamide
87
N-(4-((1R,3R,4S)-3-amino-4- hydroxycyclohexyl)pyridin-3-yl)-5- fluoro-6-(2-fluorophenyl)picolinamide
88
N-(4-((1S,3S,4R)-3-amino-4- hydroxycyclohexyl)pyridin-3-yl)-6- (2,6-difluorophenyl)-5- fluoropicolinamide
89
N-(4-(3-amino-4-hydroxy-5- methylcyclohexyl)pyridin-3-yl)-6- cyclohexyl-5-fluoropicolinamide
90
3-amino-N-(4-(3-amino-4-hydroxy-5- methylcyclohexyl)pyridin-3-yl)-6- cyclohexylpicolinamide
91
N-(4-(3-amino-5- methylcyclohexyl)pyridin-3-yl)-6- cyclohexyl-5-fluoropicolinamide
94
3-amino-N-(4-(3-amino-4-hydroxy-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)picolinamide
95
3-amino-N-(4-(3-amino-4-hydroxy-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)picolinamide
97
3-amino-N-(4-(3-amino-4-hydroxy-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)picolinamide
98
3-amino-N-(4-(3-amino-4-hydroxy-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)picolinamide
99
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
100
3-amino-N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
102
3-amino-N-(4-(3-amino-4- hydroxycyclohexyl)pyridin-3-yl)-6- (2,6-difluorophenyl)picolinamide
104
3-amino-N-(4-((1R,3S,4S)-3-amino- 4-hydroxycyclohexyl)pyridin-3-yl)-6- (2,6-difluorophenyl)picolinamide
106
3-amino-N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6- cyclohexylpicolinamide
108
N-(4-((1R,3R,5S)-3-amino-5- (trifluoromethyl)cyclohexyl)pyridin-3- yl)-6-(2-fluoro-5- methylphenyl)picolinamide
109
N-(4-((1R,3R,5S)-3-amino-5- (trifluoromethyl)cyclohexyl)pyridin-3- yl)-6-(2,6-difluoro-4- methoxyphenyl)picolinamide
110
3-amino-N-(4-((1R,3R,5S)-3-amino- 5-(trifluoromethyl)cyclohexyl)pyridin- 3-yl)-6-(2,6-difluorophenyl)-5- fluoropicolinamide
111
N-(4-((1R,3R,5S)-3-amino-5- (trifluoromethyl)cyclohexyl)pyridin-3- yl)-6-cyclohexyl-5-fluoropicolinamide
112
3-amino-N-(4-((1R,3R,5S)-3-amino- 5-(trifluoromethyl)cyclohexyl)pyridin- 3-yl)-6-(2,6- difluorophenyl)picolinamide
117
6-(2,6-Difluorophenyl)-N-(4- ((1R,3R,4R,5S)-3,4-dihydroxy-5- methylcyclohexyl)pyridin-3-yl)-5- fluoropicolinamide
121
3-amino-6-(2,6-difluorophenyl)-N-(4- ((1R,3R,4R,5S)-3,4-dihydroxy-5- methylcyclohexyl)pyridin-3-yl)-5- fluoropicolinamide
122
N-(4-((1R,5R)-5-amino-3,3- dimethylcyclohexyl)pyridin-3-yl)-6- (2,6-difluoro-4-hydroxyphenyl)-5- fluoropicolinamide
123
N-(4-((1R,5R)-5-amino-3,3- dimethylcyclohexyl)pyridin-3-yl)-6- (2,6-difluoro-4-methoxyphenyl)-5- fluoropicolinamide
124
N-(4-((1R,3S)-3- aminocyclohexyl)pyridin-3-yl)-6-(2,6- difluoro-3-hydroxyphenyl)-5- fluoropicolinamide
125
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluoro-3-hydroxyphenyl)-5- fluoropicolinamide
128
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluoro-4-hydroxyphenyl)-5- fluoropicolinamide
129
N-(4-((1R,3S,5S)-3-amino-5- methylcyclohexyl)pyridin-3-yl)-5- fluoro-6-(2,3,6- trifluorophenyl)picolinamide
130
3-amino-N-(4-(3-amino-4-hydroxy-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
131
3-amino-N-(4-(3-amino-4- hydroxycyclohexyl)pyridin-3-yl)-6- (2,6-difluorophenyl)-5- fluoropicolinamide
132
3-amino-N-(4-(3-amino-4-hydroxy-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
133
3-amino-N-(4-(3-amino-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
134
N-(4-(-3-amino-4-hydroxy-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
and
135
N-(4-(3-amino-4-hydroxy-5- methylcyclohexyl)pyridin-3-yl)-6-(2,6- difluorophenyl)-5-fluoropicolinamide
or a pharmaceutically acceptable salt thereof.
20. The compound of claim 1 , which is selected from the group consisting of:
32
35
36
38
40
51
52
63
65
66
70
76
85
94
95
98
99
100
112
122
123
124
125
128
129
130
131
132
and
133
or a pharmaceutically acceptable salt thereof.
21. A pharmaceutical composition comprising a compound of claim 10 and a pharmaceutically acceptable carrier.