US2011021525A1PendingUtilityA1
P70S6 Kinase Modulators and Method of Use
Est. expiryOct 24, 2023(expired)· nominal 20-yr term from priority
Inventors:Wei ChengErick Wang CoMoon Hwan KimRhett Ronald KleinDonna Tra LeAmy Lew TsuhakoJohn M. NussWei Xu
A61P 3/10A61P 9/10A61P 43/00A61P 37/06A61P 35/04A61P 3/04A61P 27/02A61P 29/00A61P 35/00C07D 239/42C07D 239/47C07D 239/48C07D 239/56C07D 213/85C07D 491/04C07D 239/58C07D 417/12C07D 401/12C07D 405/04C07D 409/12C07D 487/04C07D 403/12A61P 19/02A61P 17/06
43
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Claims
Abstract
The invention provides compounds and methods for inhibition of kinases, more specifically p70S6 kinases. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration, chemoinvasion and metabolism. 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.
Claims
exact text as granted — not AI-modified1 .- 36 . (canceled)
37 . A method of inhibiting the in vivo activity of p70S6K, the method comprising administering to a subject an effective amount of a composition comprising a compound according to Formula III,
III
or a pharmaceutically acceptable salt thereof, wherein:
R 1a is selected from halogen, lower perfluoroalkyl, —NO 2 , and optionally substituted C 1-4 alkyl; and R 1b is selected from halogen, —N(R 5 )R 5 , —SR 5 , perfluoroalkyl, and optionally substituted lower alkyl;
R 3 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 . —OR 5 , —N(R 5 )OR 5 , —ON(R 5 )R 5 , —N(R 5 )N(R 5 )R 5 , —N(R 5 )R 5 , —S(O) 0-2 R 5 , —SO 2 N(R 5 )R 5 , —CO 2 R 5 , —C(O)N(R 5 )R 5 , —N(R 5 )SO 2 R 5 , —N(R 5 )C(O)R 5 , —N(R 5 )CO 2 R 5 , —C(O)R 5 , —C(═NR 7 )N(R 5 )R 5 , —C(═NR 7 )R 5 , —C(═NR 7 )OR 5 , —N(R 5 )C(═NR 7 )N(R 5 )R 5 , optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkenyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, and optionally substituted arylalkyl;
R 5a is H;
each R 5 is independently selected from —H, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted lower arylalkyl, optionally substituted heterocyclyl, and optionally substituted lower heterocyclylalkyl; or
two of R 5 , together with the atom or respective atoms to which they are attached, can combine to form an optionally substituted three- to seven-membered heterocyclic;
each R 6 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —NH 2 , —OR 5 , —N(R 5 )R 5 , —S(O) 0-2 R 5 , —SO 2 N(R 5 )R 5 , —CO 2 R 5 , —C(O)N(R 5 )R 5 , —N(R 5 )SO 2 R 5 , —N(R 5 )C(O)R 5 , —N(R 5 )CO 2 R 5 , —C(O)R 5 , optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, and optionally substituted arylalkyl; or
two of R 6 , together with the atom or atoms to which they are attached, can combine to form one of an optionally substituted three to seven-membered alicylic, and an optionally substituted three to seven-membered heteroalicylic;
each R 7 is independently selected from —H, —CN, —NO 2 , —N(R 5 )R 5 , —OR 5 , —S(O) 0-2 R 5 , —SO 2 N(R 5 )R 5 , —CO 2 R 5 , optionally substituted lower alkyl, optionally substituted lower alkenyl, and optionally substituted lower alkenyl; or
R 5 and R 7 , together with the atom or atoms to which they are attached, can combine to form a five- to seven-membered optionally substituted heterocyclyl;
each of X and Y is independently selected from —C(═O)—, —C(R 6 )R 6 —, —O—, —N(R 5 )—, —C(═NR 7 )—, and —S(O) 0-2 —; provided when X is —O— or —N(R 5 )—, then Y cannot contain phenyl, napthyl, cyclohexyl, dihydronapthyl tetrahydronapthyl, or a five- to six-membered heteroaryl, each optionally substituted; and
Q is either ═N— or ═C(H)—;
wherein, when an alkyl, aryl or heterocyclyl group is substituted, one or more hydrogen atoms are replaced by a substituent independently selected from: alkyl, aryl, arylalkyl, heterocyclylalkyl, heterocyclyl, alkoxy, amino, amidino, aryloxy, arylalkyloxy, carboxy, carboalkoxy, carboxyalkyl, carboxamido, benzyloxycarbonylamino, cyano, acyl, halo, hydroxy, nitro, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, thiol, oxo, carbamyl, acylamino, and sulfonamide;
a compound selected from Table 3,
TABLE 3
Entry
Name
Structure
31
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}- N-[4-fluoro-3- (trifluoromethyl)phenyl]acetamide
34
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}- N-[4-chloro-3- (trifluoromethyl)phenyl]acetamide
55
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}- N-[2-chloro-5- (trifluoromethyl)phenyl]acetamide
62
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}- N-[2-amino-5- (trifluoromethyl)phenyl]acetamide
80
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[2- chloro-5-(trifluoromethyl)phenyl]-L- alaninamide
94
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- amino-5-(trifluoromethyl)phenyl]-L- alaninamide
112
methyl 3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoate
145
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoic acid
189
methyl 3-({N-[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoate
or a compound selected from Table 4
TABLE 4
Entry
Name
Structure
5
N 2 -[2-amino-6-(methylthio)pyrimidin- 4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
7
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [3-(methyloxy)phenyl]acetamide
9
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- (4-chlorophenyl)acetamide
11
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- (3-chlorophenyl)acetamide
14
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]acetamide
16
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- methyl-N-[3- (trifluoromethyl)phenyl]acetamide
20
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
30
2-amino-4-({2-[2,5- bis(methyloxy)phenyl]-2- oxoethyl}thio)-6- (methylthio)pyrimidine-5-carbonitrile
35
2-amino-4-(methylthio)-6-({2-oxo-1- [3-(trifluoromethyl)phenyl]pyrrolidin- 3-yl}thio)pyrimidine-5-carbonitrile
36
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [6-(trifluoromethyl)pyridin-2- yl]acetamide
37
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [4-(trifluoromethyl)pyridin-2- yl]acetamide
41
2-{[2-(acetylamino)-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [3-(trifluoromethyl)phenyl]acetamide
42
(2S)-2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]propanamide
45
2-{[2-amino-5-formyl-6- (methylamino)pyrimidin-4-yl]thio}-N- [3-(trifluoromethyl)phenyl]acetamide
46
2-{[2-amino-5-formyl-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]acetamide
54
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [2-(methyloxy)-5- (trifluoromethyl)phenyl]acetamide
58
N 2 -[2-amino-5-[(E)- hydrazonomethyl]-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
59
N 2 -[2-amino-5-[(E)- (hydroxyimino)methyl]-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
60
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
61
2-{[2-amino-5-cyano-6- (methylamino)pyrimidin-4-yl]thio}-N- [3-(trifluoromethyl)phenyl]acetamide
63
2-amino-4-(methylthio)-6-({[6- (trifluoromethyl)-1H-benzimidazol-2- yl]methyl}thio)pyrimidine-5- carbonitrile
64
2-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]hydrazine- carboxamide
65
N 2 -[5-cyano-2-(methylamino)-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
66
2-{[2-amino-5-cyano-6- (dimethylamino)pyrimidin-4-yl]thio}- N-[3- (trifluoromethyl)phenyl]acetamide
67
(S)-1-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]prolinamide
68
(2R)-2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]propanamide
69
1-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]cyclopropane- carboxamide
>
70
(2S)-2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-3- methyl-N-[3- (trifluoromethyl)phenyl]butanamide
72
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- methyl-N-[3- (trifluoromethyl)phenyl]glycinamide
73
1-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]amino}-N- [3- (trifluoromethyl)phenyl]cyclopropane- carboxamide
74
N 2 -[2-amino-5-cyano-6- (methylsulfinyl)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
75
N 2 -[2-amino-5-cyano-6- (methylsulfonyl)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
76
N 2 -(5-cyano-2-morpholin-4- ylpyrimidin-4-yl)-N-[3- (trifluoromethyl)phenyl]glycinamide
78
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
79
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[2- (methyloxy)-5- (trifluoromethyl)phenyl]-L- alaninamide
83
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-D- alaninamide
84
2-[(2-amino-5-cyano-6-morpholin-4- ylpyrimidin-4-yl)thio]-N-[3- (trifluoromethyl)phenyl]acetamide
85
(R)-1-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]prolinamide
86
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
87
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2-[2- (dimethylamino)ethyl]-N-[3- (trifluoromethyl)phenyl]glycinamide
88
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
89
N 2 -(2,6-diamino-5-cyanopyrimidin-4- yl)-N-[3-(trifluoromethyl)phenyl]-L- alaninamide
90
N 2 -(2-amino-5-cyanopyrimidin-4-yl)- N-[3-(trifluoromethyl)phenyl]-L- alaninamide
91
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- methyl-N-[3-(trifluoromethyl)phenyl]- L-alaninamide
93
2-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-1,2- dimethyl-N-[3- (trifluoromethyl)phenyl]hydrazine- carboxamide
95
ethyl [1-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-2-({[3- (trifluoromethyl)phenyl]amino} carbonyl)hydrazino]acetate
96
2-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-2-methyl- N-[3- (trifluoromethyl)phenyl]hydrazine- carboxamide
100
N 2 -[5-cyano-2-(methylthio)pyrimidin- 4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
101
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- (tetrahydro-2H-pyran-4-ylmethyl)-N- [3- (trifluoromethyl)phenyl]glycinamide
102
N 2 -(2-amino-5-cyano-6-{[2- (dimethylamino)ethyl]oxy}pyrimidin- 4-yl)-N-[3-(trifluoromethyl)phenyl]-L- alaninamide
103
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-6- {[(1,1-dimethylethyl)oxy]carbonyl}- N-[3-(trifluoromethyl)phenyl]-L- lysinamide
104
2-amino-4-(methylthio)-6- (methyl{(1S)-1-[6-(trifluoromethyl)- 1H-benzimidazol-2- yl]ethyl}amino)pyrimidine-5- carbonitrile
105
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2-[2- (tetrahydro-2H-pyran-4-yl)ethyl]-N-[3- (trifluoromethyl)phenyl]glycinamide
106
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3-{[2- (diethylamino)ethyl]amino}-5- (trifluoromethyl)phenyl]-L- alaninamide
107
2-amino-4-(methylthio)-6-({(1S)-1-[6- (trifluoromethyl)-1H-benzimidazol-2- yl]ethyl}amino)pyrimidine-5- carbonitrile
108
2-{2-amino-5-cyano-6-[1-(3- trifluoromethyl-phenylcarbamoyl)-1S- ethylamino]-pyrimidin-4-ylamino}-N- (3-trifluoromethyl-phenyl)-2S- propionamide
109
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- methyl-N-(3- methylphenyl)glycinamide
110
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- methyl-N-[3-(1- methylethyl)phenyl]glycinamide
111
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-5- [imino(nitroamino)methyl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
113
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-(3- nitrophenyl)-L-alaninamide
114
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
115
N 2 -[2-amino-5-cyano-6- (propyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
117
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- argininamide
118
N 2 -[2-amino-5-cyano-6- (methylsulfinyl)pyrimidin-4-yl]-N-2- methyl-N-[3-(trifluoromethyl)phenyl]- L-alaninamide
119
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-2- methyl-N-[3-(trifluoromethyl)phenyl]- L-alaninamide
120
N 2 -[2-amino-5-cyano-6- (propyloxy)pyrimidin-4-yl]-N-2- methyl-N-[3-(trifluoromethyl)phenyl]- L-alaninamide
121
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-2-methyl- N-[3-(trifluoromethyl)phenyl]-L- alaninamide
122
N 2 -{2-amino -5-cyano-6-[(1- methylethyl)oxy]pyrimidin-4-yl}-N- [3-(trifluoromethyl)phenyl]-L- alaninamide
123
N-5-acetyl-N-2-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
124
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-(3- aminophenyl)-L-alaninamide
125
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-N-[2- (dimethylamino)ethyl]-5- (trifluoromethyl)benzamide
126
2-(methyloxy)ethyl ((4S)-4-{[2-amino- 5-cyano-6-(methylthio)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
127
2-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]hydrazine- carboxamide
128
1,1-dimethylethyl ((4S)-4-{[2-amino- 5-cyano-6-(ethyloxy)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
130
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-methyl- L-alanyl}amino)-N-[2- (dimethylamino)ethyl]-5- (trifluoromethyl)benzamide
131
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-methyl- L-alanyl}amino)-N-[3-(4- methylpiperazin-1-yl)propyl]-5- (trifluoromethyl)benzamide
132
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~2~- methyl-N-{3- [(trifluoromethyl)oxy]phenyl}-L- alaninamide
133
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-(3- bromophenyl)-N~2~-methyl-L- alaninamide
134
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-{2-{[2- (dimethylamino)ethyl]oxy}-5- trifluoromethyl)oxy]phenyl}-N~2~- methyl-L-alaninamide
135
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-methyl- L-alanyl}amino)-N-(2-morpholin-4- ylethyl)-5-(trifluoromethyl)benzamide
136
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N~2~- methyl-N-[3-(trifluoromethyl)phenyl]- L-lysinamide
137
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3-{[2- (dimethylamino)ethyl]oxy}-5- (trifluoromethyl)phenyl]-L- alaninamide
138
(2S)-2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]amino}-3- oxo-3-{[3- (trifluoromethyl)phenyl]amino}propyl acetate
139
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~1~-[3- (trifluoromethyl)phenyl]-L- glutamamide
140
2-[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]hydrazine- carboxamide
141
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-N-hydroxy-5- (trifluoromethyl)benzamide
142
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-3- (dimethylamino)-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
143
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-5- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- norvalinamide
144
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~5~-[2- (methyloxy)ethyl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
146
methyl N~2~-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutaminate
147
N 5 -(aminocarbonyl)-N~2~-[2-amino- 5-cyano-6-(methylthio)pyrimidin-4- yl]-N-[3-(trifluoromethyl)phenyl]-L- ornithinamide
148
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
149
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutamine
150
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-serinamide
151
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-O- (phenylmethyl)-N-[3- (trifluoromethyl)phenyl]-L-serinamide
152
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- argininamide
153
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~2~- methyl-N 6 - {[(phenylmethyl)oxy]carbonyl}-N-[3- (trifluoromethyl)phenyl]-L- lysinamide
154
N-α-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- tyrosinamide
155
N 5 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
156
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]- N~6~,N~6~-dimethyl-N-[3- (trifluoromethyl)phenyl]-L- lysinamide
157
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3-[(4- methylpiperazin-1-yl)carbonyl]-5- (trifluoromethyl)phenyl]-L- alaninamide
158
3-({N-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-(3-pyrrolidin-1- ylpropyl)-5- (trifluoromethyl)benzamide
159
3-({N-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-(2-morpholin-4- ylethyl)-5-(trifluoromethyl)benzamide
160
3-({N-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-[2- (dimethylamino)ethyl]-5- (trifluoromethyl)benzamide
161
3-({N-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-[3-(4- methylpiperazin-1-yl)propyl]-5- (trifluoromethyl)benzamide
162
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N~2~- methyl-N 6 - {[(phenylmethyl)oxy]carbonyl}-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
163
1,1-dimethylethyl ((4S)-4-{[2-amino- 5-cyano-6-(ethyloxy)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
164
(2S)-2-{[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]amino}-3- oxo-3-{[3- (trifluoromethyl)phenyl]amino}propyl acetate
165
phenylmethyl N~2~-[2-amino-5- cyano-6-(ethyloxy)pyrimidin-4-yl]-N- [3-(trifluoromethyl)phenyl]-L-alpha- glutaminate
166
N 2 , N 5 -diacetyl-N~2~-[2- (acetylamino)-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
167
2-(methyloxy)ethyl ((4S)-4-{[2-amino- 5-cyano-6-(methylthio)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
168
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-5- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- norvalinamide
169
N-((4S)-4-{[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]amino}-5- oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl)- N,N-dimethylmethanaminium
170
Methyl N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutaminate
171
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]- N~6~,N~6~-dimethyl-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
172
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N~2~- methyl-N-{3- [(trifluoromethyl)oxy]phenyl}-L- alaninamide
173
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutamine
174
N~2~-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-(3- bromophenyl)-N~2~-methyl-L- alaninamide
175
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N 1 -[3- (trifluoromethyl)phenyl]-L- glutamamide
176
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-3- (dimethylamino)-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
177
2-(2-amino-5-cyano-6- ethoxypyrimidin-4-ylamino)-5- hydrazinyl-5-oxo-N-(3- (trifluoromethyl)phenyl)pentanamide
178
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-3- (dimethylamino)-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
179
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-[3-{[2- (dimethylamino)ethyl]oxy}-5- (trifluoromethyl)phenyl]-L- alaninamide
180
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3-{[2- (dimethylamino)ethyl]oxy}-5- (trifluoromethyl)phenyl]-L- alaninamide
181
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-(3- bromophenyl)-N 2 -methyl-L- alaninamide
182
phenylmethyl N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutaminate
183
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-O- (phenylmethyl)-N-[3- (trifluoromethyl)phenyl]-L-serinamide
184
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]- N~5~,N~5~-bis[2-(methyloxy)ethyl]- N-[3-(trifluoromethyl)phenyl]-L- ornithinamide
185
1,1-dimethylethyl ((4S)-4-{[2-amino- 5-cyano-6-(methyloxy)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
186
N 5 -acetyl-N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
187
N 5 ~-acetyl-N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
188
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N 2 - methyl-N-{3- [(trifluoromethyl)oxy]phenyl}-L- alaninamide
190
3-({N-[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-[2- (dimethylamino)ethyl]-5- (trifluoromethyl)benzamide
191
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-3- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
192
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-3- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
193
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-3- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
194
N 5 -(aminocarbonyl)-N 2 -[2-amino-5- cyano-6-(ethyloxy)pyrimidin-4-yl]-N- [3-(trifluoromethyl)phenyl]-L- ornithinamide
195
N~2~-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-D-lysinamide
196
N 2 -[2-amino-5-cyano-6- ((ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-D-lysinamide
197
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-O-methyl- N-[3-(trifluoromethyl)phenyl]-L- serinamide
198
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~5~- (methylsulfonyl)-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
and a pharmaceutically acceptable carrier.
38 . (canceled)
39 . (canceled)
40 . A method of treating a disease or disorder associated with uncontrolled, abnormal, and/or unwanted cellular activities, the method comprising administering, to a mammal in need thereof, a therapeutically effective amount of a composition comprising a compound according to Formula III,
or a pharmaceutically acceptable salt thereof, wherein:
R 1a is selected from halogen, lower perfluoroalkyl, —NO 2 and optionally substituted C 1-4 alkyl; and R 1b is selected from halogen, —N(R 5 )R 5 , —SR 5 , perfluoroalkyl, and optionally substituted lower alkyl;
R 3 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —OR 5 , —N(R 5 )OR 5 , —ON(R 5 )R 5 , —N(R 5 )N(R 5 )R 5 , —N(R 5 )R 5 , —S(O) 0-2 R 5 , —SO 2 N(R 5 )R 5 , —CO 2 R 5 , —C(O)N(R 5 )R 5 , —N(R 5 )SO 2 R 5 , —N(R 5 )C(O)R 5 , —N(R 5 )CO 2 R 5 , —C(O)R 5 , —C(═NR 7 )N(R 5 )R 5 , —C(═NR 7 )R 5 , —C(═NR 7 )OR 5 , —N(R 5 )C(═NR 7 )N(R 5 )R 5 , optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, and optionally substituted arylalkyl;
R 5a is H;
each R 5 is independently selected from —H, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted lower arylalkyl, optionally substituted heterocyclyl, and optionally substituted lower heterocyclylalkyl; or
two of R 5 , together with the atom or respective atoms to which they are attached, can combine to form an optionally substituted three- to seven-membered heterocyclic;
each R 6 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —NH 2 , —OR 5 , —N(R 5 )R 5 , —S(O) 0-2 R 5 , —SO 2 N(R 5 )R 5 , —CO 2 R 5 , —C(O)N(R 5 )R 5 , —N(R 5 )SO 2 R 5 , —N(R 5 )C(O)R 5 , —N(R 5 )CO 2 R 5 , —C(O)R 5 , optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, and optionally substituted arylalkyl; or
two of R 6 , together with the atom or atoms to which they are attached, can combine to form one of an optionally substituted three to seven-membered alicylic, and an optionally substituted three to seven-membered heteroalicylic;
each R 7 is independently selected from —H, —CN, —NO 2 , —N(R 5 )R 5 , —OR 5 , —S(O) 0-2 R 5 , —SO 2 N(R 5 )R 5 , —CO 2 R 5 , optionally substituted lower alkyl, optionally substituted lower alkenyl, and optionally substituted lower alkenyl; or
R 5 and R 7 , together with the atom or atoms to which they are attached, can combine to form a five- to seven-membered optionally substituted heterocyclyl;
each of X and Y is independently selected from —C(═O)—, —C(R 6 )R 6 —, —O—, —N(R 5 )—, —C(═NR 7 )—, and —S(O) 0-2 —; provided when X is —O— or —N(R 5 )—, then Y cannot contain phenyl, napthyl, cyclohexyl, dihydronapthyl tetrahydronapthyl, or a five- to six-membered heteroaryl, each optionally substituted; and
Q is either ═N— or ═C(H)—;
wherein, when an alkyl, aryl or heterocyclyl group is substituted, one or more hydrogen atoms are replaced by a substituent independently selected from: alkyl, aryl, arylalkyl, heterocyclylalkyl, heterocyclyl, alkoxy, amino, amidino, aryloxy, arylalkyloxy, carboxy, carboalkoxy, carboxyalkyl, carboxamido, benzyloxycarbonylamino, cyano, acyl, halo, hydroxy, nitro, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, thiol, oxo, carbamyl, acylamino, and sulfonamide;
or a compound selected from Table 3
Entry
Name
Structure
31
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}- N-[4-fluoro-3- (trifluoromethyl)phenyl]acetamide
34
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}- N-[4-chloro-3- (trifluoromethyl)phenyl]acetamide
55
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}- N-[2-chloro-5- (trifluoromethyl)phenyl]acetamide
62
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}- N-[2-amino-5- (trifluoromethyl)phenyl]acetamide
80
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]- N-[2-chloro-5- (trifluoromethyl)phenyl]-L- alaninamide
94
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]- N-[3-amino-5- (trifluoromethyl)phenyl]-L- alaninamide
112
methyl 3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino-5- trifluoromethyl)benzoate
145
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoic acid
189
methyl 3-({N-[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-L- alanyl}amino-5- trifluoromethyl)benzoate
or a compound selected from Table 4
TABLE 4
Entry
Name
Structure
5
N 2 -[2-amino-6-(methylthio)pyrimidin- 4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
7
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [3-(methyloxy)phenyl]acetamide
9
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- (4-chlorophenyl)acetamide
11
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- (3-chlorophenyl)acetamide
14
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]acetamide
16
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- methyl-N-[3- (trifluoromethyl)phenyl]acetamide
20
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- trifluoromethyl)phenyl]glycinamide
30
2-amino-4-({2-[2,5- bis(methyloxy)phenyl]-2- oxoethyl}thio)-6- (methylthio)pyrimidine-5-carbonitrile
35
2-amino-4-(methylthio)-6-({2-oxo-1- [3-(trifluoromethyl)phenyl]pyrrolidin- 3-yl}thio)pyrimidine-5-carbonitrile
36
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [6-(trifluoromethyl)pyridin-2- yl]acetamide
37
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl-N- [4-(trifluoromethyl)pyridin-2- yl]acetamide
41
2-{[2-(acetylamino)-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [3-(trifluoromethyl)phenyl]acetamide
42
(2S)-2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]propanamide
45
2-{[2-amino-5-formyl-6- (methylamino)pyrimidin-4-yl]thio}-N- [3-(trifluoromethyl)phenyl]acetamide
46
2-{[2-amino-5-formyl-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]acetamide
54
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [2-(methyloxy)-5- (trifluoromethyl)phenyl]acetamide
58
N 2 -[2-amino-5-[(E)- hydrazonomethyl]-6- methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
59
N 2 -[2-amino-5-[(E)- (hydroxyimino)methyl]-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
60
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
61
2-{[2-amino-5-cyano-6- (methylamino)pyrimidin-4-yl]thio}-N- [3-(trifluoromethyl)phenyl]acetamide
63
2-amino-4-(methylthio)-6-({[6- (trifluoromethyl)-1H-benzimidazol-2- yl]methyl}thio)pyrimidine-5- carbonitrile
64
2-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- trifluoromethyl)phenyl]hydrazinecarb oxamide
65
N 2 -[5-cyano-2-(methylamino)-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
66
2-{[2-amino-5-cyano-6- (dimethylamino)pyrimidin-4-yl]thio}- N-[3- (trifluoromethyl)phenyl]acetamide
67
(S)-1-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]prolinamide
68
(2R)-2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]propanamide
69
1-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]cyclopropane carboxamide
70
(2S)-2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-3- methyl-N-[3- (trifluoromethyl)phenyl]butanamide
72
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- methyl-N-[3- (trifluoromethyl)phenyl]glycinamide
73
1-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]amino}-N- [3- (trifluoromethyl)phenyl]cyclopropane carboxamide
74
N 2 -[2-amino-5-cyano-6- (methylsulfinyl)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
75
N 2 -[2-amino-5-cyano-6- (methylsulfonyl)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
76
N 2 -(5-cyano-2-morpholin-4- ylpyrimidin-4-yl)-N-[3- (trifluoromethyl)phenyl]glycinamide
78
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
79
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[2- (methyloxy)-5- (trifluoromethyl)phenyl]-L- alaninamide
83
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-D- alaninamide
84
2-[(2-amino-5-cyano-6-morpholin-4- ylpyrimidin-4-yl)thio]-N-[3- (trifluoromethyl)phenyl]acetamide
85
(R)-1-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]prolinamide
86
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
87
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2-[2- (dimethylamino)ethyl]-N-[3- (trifluoromethyl)phenyl]glycinamide
88
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
89
N 2 -(2,6-diamino-5-cyanopyrimidin-4- yl)-N-[3-(trifluoromethyl)phenyl]-L- alaninamide
90
N 2 -(2-amino-5-cyanopyrimidin-4-yl)- N-[3-(trifluoromethyl)phenyl]-L- alaninamide
91
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- methyl-N-[3-(trifluoromethyl)phenyl]- L-alaninamide
93
2-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-1,2- dimethyl-N-[3- (trifluoromethyl)phenyl]hydrazinecarb oxamide
95
ethyl [1-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-2-({[3- (trifluoromethyl)phenyl]amino}carbon yl)hydrazino]acetate
96
2-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-2-methyl- N-[3- (trifluoromethyl)phenyl]hydrazinecarb oxamide
100
N 2 -[5-cyano-2-(methylthio)pyrimidin- 4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
101
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- (tetrahydro-2H-pyran-4-ylmethyl)-N- [3- (trifluoromethyl)phenyl]glycinamide
102
N 2 -(2-amino-5-cyano-6-{[2- (dimethylamino)ethyl]oxy}pyrimidin- 4-yl)-N[3-(trifluoromethyl)phenyl]-L- alaninamide
103
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-6- {[(1,1-dimethylethyl)oxy]carbonyl}- N-[3-(trifluoromethyl)phenyl]-L- lysinamide
104
2-amino-4-(methylthio)-6- (methyl{(1S)-1-[6-(trifluoromethyl)- 1H-benzimidazol-2- yl]ethyl}amino)pyrimidine-5- carbonitrile
105
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2-[2- (tetrahydro-2H-pyran-4-yl)ethyl]-N-[3- (trifluoromethyl)phenyl]glycinamide
106
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3-{[2- (diethylamino)ethyl]amino}-5- (trifluoromethyl)phenyl]-L- alaninamide
107
2-amino-4-(methylthio)-6-({(1S)-1-[6- (trifluoromethyl)-1H-benzimidazol-2- yl]ethyl}amino)pyrimidine-5- carbonitrile
108
2-{2-amino-5-cyano-6-[1-(3- trifluoromethyl-phenylcarbamoyl)-1S- ethylamino]-pyrimidin-4-ylamino}-N- (3-trifluoromethyl-phenyl)-2S- propionamide
109
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- methyl-N-(3- methylphenyl)glycinamide
110
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- methyl-N-[3-(1- methylethyl)phenyl]glycinamide
111
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-5- [imino(nitroamino)methyl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
113
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-(3- nitrophenyl)-L-alaninamide
114
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
115
N 2 -[2-amino-5-cyano-6- (propyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
117
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- argininamide
118
N 2 -[2-amino-5-cyano-6- (methylsulfinyl)pyrimidin-4-yl]-N-2- methyl-N-[3-(trifluoromethyl)phenyl]- L-alaninamide
119
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-2- methyl-N-[3-(trifluoromethyl)phenyl]- L-alaninamide
120
N 2 -[2-amino-5-cyano-6- (propyloxy)pyrimidin-4-yl]-N-2- methyl-N-[3-(trifluoromethyl)phenyl]- L-alaninamide
121
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-2-methyl- N-[3-(trifluoromethyl)phenyl]-L- alaninamide
122
N 2 -{2-amino-5-cyano-6-[(1- methylethyl)oxylpyrimidin-4-yl}-N- [3-(trifluoromethyl)phenyl]-L- alaninamide
123
N-5-acetyl-N-2-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
124
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-(3- aminophenyl)-L-alaninamide
125
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-N-[2- (dimethylamino)ethyl]-5- (trifluoromethyl)benzamide
126
2-(methyloxy)ethyl ((4S)-4-{[2-amino- 5-cyano-6-(methylthio)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
127
2-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]hydrazinecarb oxamide
128
1,1-dimethylethyl ((4S)-4-{[2-amino- 5-cyano-6-(ethyloxy)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
130
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-methyl- L-alanyl}amino)-N-[2- (dimethylamino)ethyl]-5- (trifluoromethyl)benzamide
131
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-methyl- L-alanyl}amino)-N-[3-(4- methylpiperazin-1-yl)propyl]-5- (trifluoromethyl)benzamide
132
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~2~- methyl-N-{3- [(trifluoromethyl)oxy]phenyl}-L- alaninamide
133
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-(3- bromophenyl)-N~2~-methyl-L- alaninamide
134
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-{2-{[2- (dimethylamino)ethyl]oxy}-5- [(trifluoromethyl)oxylphenyl}-N~2~- methyl-L-alaninamide
135
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-methyl- L-alanyl}amino)-N-(2-morpholin-4- ylethyl)-5-(trifluoromethyl)benzamide
136
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N~2~- methyl-N-[3-(trifluoromethyl)phenyl]- L-lysinamide
137
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3-{[2- (dimethylamino)ethyl]oxy}-5- (trifluoromethyl)phenyl]-L- alaninamide
138
(2S)-2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]amino}-3- oxo-3-{[3- (trifluoromethyl)phenyl]amino}propyl acetate
139
N 2 -[2-amino-5 -cyano-6- (methylthio)pyrimidin-4-yl]-N~1~-[3- (trifluoromethyl)phenyl]-L- glutamamide
140
2-[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]hydrazinecarb oxamide
141
3 -({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-N-hydroxy-5- (trifluoromethyl)benzamide
142
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-3- (dimethylamino)-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
143
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-5- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- norvalinamide
144
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~5~-[2- (methyloxy)ethyl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
146
methyl N~2~-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutaminate
147
N 5 -(aminocarbonyl)-N~2~-[2-amino- 5-cyano-6-(methylthio)pyrimidin-4- yl]-N-[3-(trifluoromethyl)phenyl]-L- ornithinamide
148
N 2 -[2-amino-5-cyano-6- ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
149
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutamine
150
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-serinamide
151
N 2 -[2-amino-5-cyano-6- ethyloxy)pyrimidin-4-yl]-O- (phenylmethyl)-N-[3- (trifluoromethyl)phenyl]-L-serinamide
152
N 2 -[2-amino-5-cyano-6- ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- argininamide
153
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~2~- methyl-N 6 - {[(phenylmethyl)oxy]carbonyl}-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
154
N-α-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- tyrosinamide
155
N 5 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
156
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]- N~6~,N~6~-dimethyl-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
157
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3-[(4- methylpiperazin-1-yl)carbonyl]-5- (trifluoromethyl)phenyl]-L- alaninamide
158
3-({N-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-(3-pyrrolidin-1- ylpropyl)-5- (trifluoromethyl)benzamide
159
3-({N-[2-amino-5-cyano-6- ethyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-(2-morpholin-4- ylethyl)-5-(trifluoromethyl)benzamide
160
3-({N-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-[2- (dimethylamino)ethyl]-5- (trifluoromethyl)benzamide
161
3-({N-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-[3-(4- methylpiperazin-1-yl)propyl]-5- (trifluoromethyl)benzamide
162
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N~2~- methyl-N 6 - {[(phenylmethyl)oxy]carbonyl}-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
163
1,1-dimethylethyl ((4S)-4-{[2-amino- 5-cyano-6-(ethyloxy)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
164
(2S)-2-{[2-amino-5-cyano-6- ethyloxy)pyrimidin-4-yl]amino}-3- oxo-3-{[3- (trifluoromethyl)phenyl]amino}propyl acetate
165
phenylmethyl N~2~-[2-amino-5- cyano-6-(ethyloxy)pyrimidin-4-yl]-N- [3-(trifluoromethyl)phenyl]-L-alpha- glutaminate
166
N 2 , N 5 -diacetyl-N~2~-[2- (acetylamino)-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
167
2-(methyloxy)ethyl ((4S)-4-{[2-amino- 5-cyano-6-(methylthio)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
168
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-5- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- norvalinamide
169
N-((4S)-4-{[2-amino-5-cyano-6- ethyloxy)pyrimidin-4-yl]amino}-5- oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl)- N,N-dimethylmethanaminium
170
Methyl N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutaminate
171
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]- N~6~,N~6~-dimethyl-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
172
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N~2~- methyl-N-{3- [(trifluoromethyl)oxy]phenyl}-L- alaninamide
173
N-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutamine
174
N~2~-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-(3- bromophenyl)-N~2~-methyl-L- alaninamide
175
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N 1 -[3- (trifluoromethyl)phenyl]-L- glutamamide
176
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-3- (dimethylamino)-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
177
2-(2-amino-5-cyano-6- ethoxypyrimidin-4-ylamino)-5- hydrazinyl-5-oxo-N-(3- (trifluoromethyl)phenyl)pentanamide
178
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-3- (dimethylamino)-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
179
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-[3-{[2- (dimethylamino)ethyl]oxy}-5- (trifluoromethyl)phenyl]-L- alaninamide
180
N 2 -[2-amino-5-cyano-6- ethyloxy)pyrimidin-4-yl]-N-[3-{[2- (dimethylamino)ethyl]oxy}-5- trifluoromethyl)phenyl]-L- alaninamide
181
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-(3- bromophenyl)-N 2 -methyl-L- alaninamide
182
phenylmethyl N 2 -[2-amino-5-cyano-6- methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutaminate
183
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-O- (phenylmethyl)-N-[3- (trifluoromethyl)phenyl]-L-serinamide
184
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]- N~5~,N~5~-bis[2-(methyloxy)ethyl]- N-[3-(trifluoromethyl)phenyl]-L- ornithinamide
185
1,1-dimethylethyl ((4S)-4-{[2-amino- 5-cyano-6-(methyloxy)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
186
N 5 -acetyl- N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
187
N 5 ~-acetyl-N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
188
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N 2 - methyl-N-{3- [(trifluoromethyl)oxy]phenyl}-L- alaninamide
190
3-({N-[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-[2- (dimethylamino)ethyl]-5- (trifluoromethyl)benzamide
191
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-3- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
192
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-3- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
193
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-3- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
194
N 5 -(aminocarbonyl)-N 2 -[2-amino-5- cyano-6-(ethyloxy)pyrimidin-4-yl]-N- [3-(trifluoromethyl)phenyl]-L- ornithinamide
195
N~2~-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-D-lysinamide
196
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-D-lysinamide
197
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-O-methyl- N-[3-(trifluoromethyl)phenyl]-L- serinamide
198
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~5~- (methylsulfonyl)-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
and
a pharmaceutically acceptable carrier.
41 . (canceled)
42 . A method of inhibiting proliferative activity in a cell, the method comprising administering an effective amount of a compound according to Formula III,
or a pharmaceutically acceptable salt thereof, wherein:
R 1a is selected from halogen, lower perfluoroalkyl, —NO 2 , and optionally substituted C 1-4 alkyl; and R 1b is selected from halogen, —N(R 5 )R 5 , —SR 5 , perfluoroalkyl, and optionally substituted lower alkyl;
R 3 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —OR 5 , —N(R 5 )OR 5 , —ON(R 5 )R 5 , —N(R 5 )N(R 5 )R 5 , —N(R 5 )R 5 , —S(O) 0-2 R 5 , —SO 2 N(R 5 )R 5 , —CO 2 R 5 , —C(O)N(R 5 )R 5 , —N(R 5 )SO 2 R 5 , —N(R 5 )C(O)R 5 , —N(R 5 )CO 2 R 5 , —C(O)R 5 , —C(═NR 7 )N(R 5 )R 5 , —C(═NR 7 )R 5 , —C(═NR 7 )OR 5 , —N(R 5 )C(═NR 7 )N(R 5 )R 5 , optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkenyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, and optionally substituted arylalkyl;
R 5a is H;
each R 5 is independently selected from —H, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted lower arylalkyl, optionally substituted heterocyclyl, and optionally substituted lower heterocyclylalkyl; or
two of R 5 , together with the atom or respective atoms to which they are attached, can combine to form an optionally substituted three- to seven-membered heterocyclic;
each R 6 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —NH 2 , —OR 5 , —N(R 5 )R 5 , —S(O) 0-2 R 5 , —SO 2 N(R 5 )R 5 , —CO 2 R 5 , —C(O)N(R 5 )R 5 , —N(R 5 )SO 2 R 5 , —N(R 5 )C(O)R 5 , —N(R 5 )CO 2 R 5 , —C(O)R 5 , optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, and optionally substituted arylalkyl; or
two of R 6 , together with the atom or atoms to which they are attached, can combine to form one of an optionally substituted three to seven-membered alicylic, and an optionally substituted three to seven-membered heteroalicylic;
each R 7 is independently selected from —H, —CN, —NO 2 , —N(R 5 )R 5 , —OR 5 , —S(O) 0-2 R 5 , —SO 2 N(R 5 )R 5 , —CO 2 R 5 , optionally substituted lower alkyl, optionally substituted lower alkenyl, and optionally substituted lower alkenyl; or
R 5 and R 7 , together with the atom or atoms to which they are attached, can combine to form a five- to seven-membered optionally substituted heterocyclyl;
each of X and Y is independently selected from —C(═O)—, —C(R 6 )R 6 —, —O—, —N(R 5 )—, —C(═NR 7 )—, and —S(O) 0-2 —; provided when X is —O— or —N(R 5 )—, then Y cannot contain phenyl, napthyl, cyclohexyl, dihydronapthyl tetrahydronapthyl, or a five- to six-membered heteroaryl, each optionally substituted; and
Q is either ═N— or ═C(H)—;
wherein, when an alkyl, aryl or heterocyclyl group is substituted, one or more hydrogen atoms are replaced by a substituent independently selected from: alkyl, aryl, arylalkyl, heterocyclylalkyl, heterocyclyl, alkoxy, amino, amidino, aryloxy, arylalkyloxy, carboxy, carboalkoxy, carboxyalkyl, carboxamido, benzyloxycarbonylamino, cyano, acyl, halo, hydroxy, nitro, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, thiol, oxo, carbamyl, acylamino, and sulfonamide;
or a compound selected from Table 3
TABLE 3
Entry
Name
Structure
31
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [4-fluoro-3- (trifluoromethyl)phenyl]acetamide
34
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [4-chloro-3- (trifluoromethyl)phenyl]acetamide
55
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [2-chloro-5- (trifluoromethyl)phenyl]acetamide
62
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [2-amino-5- (trifluoromethyl)phenyl]acetamide
80
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[2- chloro-5-(trifluoromethyl)phenyl]-L- alaninamide
94
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- amino-5-(trifluoromethyl)phenyl]-L- alaninamide
112
methyl 3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoate
145
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoic acid
189
methyl 3-({N-[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoate
or a compound selected from Table 4
TABLE 4
Entry
Name
Structure
5
N 2 -[2-amino-6-(methylthio)pyrimidin- 4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
7
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [3-(methyloxy)phenyl]acetamide
9
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- (4-chlorophenyl)acetamide
11
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- (3-chlorophenyl)acetamide
14
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]acetamide
16
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- methyl-N-[3- (trifluoromethyl)phenyl]acetamide
20
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
30
2-amino-4-({2-[2,5- bis(methyloxy)phenyl]-2- oxoethyl}thio)-6- (methylthio)pyrimidine-5-carbonitrile
35
2-amino-4-(methylthio)-6-({2-oxo-1- [3-(trifluoromethyl)phenyl]pyrrolidin- 3-yl}thio)pyrimidine-5-carbonitrile
36
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [6-(trifluoromethyl)pyridin-2- yl]acetamide
37
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [4-(trifluoromethyl)pyridin-2- yl]acetamide
41
2-{[2-(acetylamino)-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [3-(trifluoromethyl)phenyl]acetamide
42
(2S)-2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]propanamide
45
2-{[2-amino-5-formyl-6- (methylamino)pyrimidin-4-yl]thio}-N- [3-(trifluoromethyl)phenyl]acetamide
46
2-{[2-amino-5-formyl-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]acetamide
54
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [2-(methyloxy)-5- (trifluoromethyl)phenyl]acetamide
58
N 2 -[2-amino-5-[(E)- hydrazonomethyl]-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
59
N 2 -[2-amino-5-[(E)- (hydroxyimino)methyl]-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
60
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
61
2-{[2-amino-5-cyano-6- (methylamino)pyrimidin-4-yl]thio}-N- [3-(trifluoromethyl)phenyl]acetamide
63
2-amino-4-(methylthio)-6-({[6- (trifluoromethyl)-1H-benzimidazol-2- yl]methyl}thio)pyrimidine-5- carbonitrile
64
2-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]hydrazine- carboxamide
65
N 2 -[5-cyano-2-(methylamino)-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
66
2-{[2-amino-5-cyano-6- (dimethylamino)pyrimidin-4-yl]thio}- N-[3- (trifluoromethyl)phenyl]acetamide
67
(S)-1-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]prolinamide
68
(2R)-2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]propanamide
69
1-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-N-[3- (trifluoromethyl)phenyl]cyclopropane- carboxamide
70
(2S)-2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]oxy}-3- methyl-N-[3- (trifluoromethyl)phenyl]butanamide
72
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- methyl-N-[3- (trifluoromethyl)phenyl]glycinamide
73
1-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]amino}-N- [3- (trifluoromethyl)phenyl]cyclopropane- carboxamide
74
N 2 -[2-amino-5-cyano-6- (methylsulfinyl)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
75
N 2 -[2-amino-5-cyano-6- (methylsulfonyl)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
76
N 2 -(5-cyano-2-morpholin-4- ylpyrimidin-4-yl)-N-[3- (trifluoromethyl)phenyl]glycinamide
78
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
79
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[2- (methyloxy)-5- (trifluoromethyl)phenyl]-L- alaninamide
83
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-D- alaninamide
84
2-[(2-amino-5-cyano-6-morpholin-4- ylpyrimidin-4-yl)thio]-N-[3- (trifluoromethyl)phenyl]acetamide
85
(R)-1-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]prolinamide
86
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
87
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2-[2- (dimethylamino)ethyl]-N-[3- (trifluoromethyl)phenyl]glycinamide
88
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
89
N 2 -(2,6-diamino-5-cyanopyrimidin-4- yl)-N-[3-(trifluoromethyl)phenyl]-L- alaninamide
90
N 2 -(2-amino-5-cyanopyrimidin-4-yl)- N-[3-(trifluoromethyl)phenyl]-L- alaninamide
91
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- methyl-N-[3-(trifluoromethyl)phenyl]- L-alaninamide
93
2-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-1,2- dimethyl-N-[3- (trifluoromethyl)phenyl]hydrazine- carboxamide
95
ethyl [1-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-2-({[3- (trifluoromethyl)phenyl]amino}carbon- yl)hydrazino]acetate
96
2-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-2-methyl- N-[3- (trifluoromethyl)phenyl]hydrazine- carboxamide
100
N 2 -[5-cyano-2-(methylthio)pyrimidin- 4-yl]-N-[3- (trifluoromethyl)phenyl]glycinamide
101
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- (tetrahydro-2H-pyran-4-ylmethyl)-N- [3- (trifluoromethyl)phenyl]glycinamide
102
N 2 -(2-amino-5-cyano-6-{[2- (dimethylamino)ethyl]oxy}pyrimidin- 4-yl)-N-[3-(trifluoromethyl)phenyl]-L- alaninamide
103
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-6- {[(1,1-dimethylethyl)oxy]carbonyl}- N-[3-(trifluoromethyl)phenyl]-L- lysinamide
104
2-amino-4-(methylthio)-6- (methyl{(1S)-1-[6-(trifluoromethyl)- 1H-benzimidazol-2- yl]ethyl}amino)pyrimidine-5- carbonitrile
105
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2-[2- (tetrahydro-2H-pyran-4-yl)ethyl]-N-[3- (trifluoromethyl)phenyl]glycinamide
106
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3-{[2- (diethylamino)ethyl]amino}-5- (trifluoromethyl)phenyl]-L- alaninamide
107
2-amino-4-(methylthio)-6-({(1S)-1-[6- (trifluoromethyl)-1H-benzimidazol-2- yl]ethyl}amino)pyrimidine-5- carbonitrile
108
2-{2-amino-5-cyano-6-[1-(3- trifluoromethyl-phenylcarbamoyl)-1S- ethylamino]-pyrimidin-4-ylamino}-N- (3-trifluoromethyl-phenyl)-2S- propionamide
109
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- methyl-N-(3- methylphenyl)glycinamide
110
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-2- methyl-N-[3-(1- methylethyl)phenyl]glycinamide
111
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-5- [imino(nitroamino)methyl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
113
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-(3- nitrophenyl)-L-alaninamide
114
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
115
N 2 -[2-amino-5-cyano-6- (propyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
117
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- argininamide
118
N 2 -[2-amino-5-cyano-6- (methylsulfinyl)pyrimidin-4-yl]-N-2- methyl-N-[3-(trifluoromethyl)phenyl]- L-alaninamide
119
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-2- methyl-N-[3-(trifluoromethyl)phenyl]- L-alaninamide
120
N 2 -[2-amino-5-cyano-6- (propyloxy)pyrimidin-4-yl]-N-2- methyl-N-[3-(trifluoromethyl)phenyl]- L-alaninamide
121
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-2-methyl- N-[3-(trifluoromethyl)phenyl]-L- alaninamide
122
N 2 -{2-amino-5-cyano-6-[(1- methylethyl)oxy]pyrimidin-4-yl}-N- [3-(trifluoromethyl)phenyl]-L- alaninamide
123
N-5-acetyl-N-2-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
124
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-(3- aminophenyl)-L-alaninamide
125
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-N-[2- (dimethylamino)ethyl]-5- (trifluoromethyl)benzamide
126
2-(methyloxy)ethyl ((4S)-4-{[2-amino- 5-cyano-6-(methylthio)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
127
2-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]hydrazine- carboxamide
128
1,1-dimethylethyl ((4S)-4-{[2-amino- 5-cyano-6-(ethyloxy)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
130
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-methyl- L-alanyl}amino)-N-[2- (dimethylamino)ethyl]-5- (trifluoromethyl)benzamide
131
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-methyl- L-alanyl}amino)-N-[3-(4- methylpiperazin-1-yl)propyl]-5- (trifluoromethyl)benzamide
132
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~2~- methyl-N-{3- [(trifluoromethyl)oxy]phenyl}-L- alaninamide
133
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-(3- bromophenyl)-N~2~-methyl-L- alaninamide
134
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-{2-{[2- (dimethylamino)ethyl]oxy}-5- (trifluoromethyl)oxy]phenyl}-N~2~- methyl-L-alaninamide
135
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-methyl- L-alanyl}amino)-N-(2-morpholin-4- ylethyl)-5-(trifluoromethyl)benzamide
136
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N~2~- methyl-N-[3-(trifluoromethyl)phenyl]- L-lysinamide
137
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3-{[2- (dimethylamino)ethyl]oxy}-5- (trifluoromethyl)phenyl]-L- alaninamide
138
(2S)-2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]amino}-3- oxo-3-{[3- (trifluoromethyl)phenyl]amino}propyl acetate
139
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~1~-[3- (trifluoromethyl)phenyl]-L- glutamamide
140
2-[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]hydrazine- carboxamide
141
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-N-hydroxy-5- (trifluoromethyl)benzamide
142
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-3- (dimethylamino)-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
143
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-5- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- norvalinamide
144
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~5~-[2- (methyloxy)ethyl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
146
methyl N~2~-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutaminate
147
N 5 -(aminocarbonyl)-N~2~-[2-amino- 5-cyano-6-(methylthio)pyrimidin-4- yl]-N-[3-(trifluoromethyl)phenyl]-L- ornithinamide
148
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
149
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutamine
150
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-serinamide
151
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-O- (phenylmethyl)-N-[3- (trifluoromethyl)phenyl]-L-serinamide
152
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- argininamide
153
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~2~- methyl-N 6 - {[(phenylmethyl)oxy]carbonyl}-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
154
N-α-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- tyrosinamide
155
N 5 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
156
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]- N~6~,N~6~-dimethyl-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
157
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3-[(4- methylpiperazin-1-yl)carbonyl]-5- (trifluoromethyl)phenyl]-L- alaninamide
158
3-({N-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-(3-pyrrolidin-1- ylpropyl)-5- (trifluoromethyl)benzamide
159
3-({N-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-(2-morpholin-4- ylethyl)-5-(trifluoromethyl)benzamide
160
3-({N-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-[2- (dimethylamino)ethyl]-5- (trifluoromethyl)benzamide
161
3-({N-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-[3-(4- methylpiperazin-1-yl)propyl]-5- (trifluoromethyl)benzamide
162
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N~2~- methyl-N 6 - {[(phenylmethyl)oxy]carbonyl}-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
163
1,1-dimethylethyl ((4S)-4-{[2-amino- 5-cyano-6-(ethyloxy)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
164
(2S)-2-{[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]amino}-3- oxo-3-{[3- (trifluoromethyl)phenyl]amino}propyl acetate
165
phenylmethyl N~2~-[2-amino-5- cyano-6-(ethyloxy)pyrimidin-4-yl]-N- [3-(trifluoromethyl)phenyl]-L-alpha- glutaminate
166
N 2 ,N 5 -diacetyl-N~2~-[2- (acetylamino)-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
167
2-(methyloxy)ethyl ((4S)-4-{[2-amino- 5-cyano-6-(methylthio)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
168
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-5- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- norvalinamide
169
N-((4S)-4-{[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]amino}-5- oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl)- N,N-dimethylmethanaminium
170
Methyl N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutaminate
171
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]- N~6~,N~6~-dimethyl-N-[3- (trifluoromethyl)phenyl]-L-lysinamide
172
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N~2~- methyl-N-{3- [(trifluoromethyl)oxy]phenyl}-L- alaninamide
173
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha glutamine
174
N~2~-[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-(3- bromophenyl)-N~2~-methyl-L- alaninamide
175
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N 1 -[3- (trifluoromethyl)phenyl]-L- glutamamide
176
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-3- (dimethylamino)-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
177
2-(2-amino-5-cyano-6- ethoxypyrimidin-4-ylamino)-5- hydrazinyl-5-oxo-N-(3- (trifluoromethyl)phenyl)pentanamide
178
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-3- (dimethylamino)-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
179
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-[3-{[2- (dimethylamino)ethyl]oxy}-5- (trifluoromethyl)phenyl]-L- alaninamide
180
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3-{[2- (dimethylamino)ethyl]oxy}-5- (trifluoromethyl)phenyl]-L- alaninamide
181
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N-(3- bromophenyl)-N 2 -methyl-L- alaninamide
182
phenylmethyl N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L-alpha- glutaminate
183
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-O- (phenylmethyl)-N-[3- (trifluoromethyl)phenyl]-L-serinamide
184
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]- N~5~,N~5~-bis[2-(methyloxy)ethyl]- N-[3-(trifluoromethyl)phenyl]-L- ornithinamide
185
1,1-dimethylethyl ((4S)-4-{[2-amino- 5-cyano-6-(methyloxy)pyrimidin-4- yl]amino}-5-oxo-5-{[3- (trifluoromethyl)phenyl]amino}pentyl) carbamate
186
N 5 -acetyl-N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
187
N 5 ~-acetyl-N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
188
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-N 2 - methyl-N-{3- [(trifluoromethyl)oxy]phenyl}-L- alaninamide
190
3-({N-[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-L- alanyl}amino)-N-[2- (dimethylamino)ethyl]-5- (trifluoromethyl)benzamide
191
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-3- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
192
N 2 -[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-3- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
193
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-3- morpholin-4-yl-N-[3- (trifluoromethyl)phenyl]-L- alaninamide
194
N 5 -(aminocarbonyl)-N 2 -[2-amino-5- cyano-6-(ethyloxy)pyrimidin-4-yl]-N- [3-(trifluoromethyl)phenyl]-L- ornithinamide
195
N~2~-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-D-lysinamide
196
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-N-[3- (trifluoromethyl)phenyl]-D-lysinamide
197
N 2 -[2-amino-5-cyano-6- (ethyloxy)pyrimidin-4-yl]-O-methyl- N-[3-(trifluoromethyl)phenyl]-L- serinamide
198
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N~5~- (methylsufonyl)-N-[3- (trifluoromethyl)phenyl]-L- ornithinamide
and
a pharmaceutically acceptable carrier.
43 . (canceled)
44 . The method of claim 40 , wherein the disease or disorder is cancer, an immunological disorder, rheumatoid arthritis, graft-host disease, multiple sclerosis, psoriasis, cardiovascular disease, artheroscrosis, myocardioinfarction, ischemia, stroke, restenosis, metabolic disorder, diabetes, obesity, hypercholesterolemia, inflammatory disease, degenerative disease, interbowel disease, osteoarthritus, macular degeneration, or diabetic retinopathy.
45 . The method of claim 44 , wherein the cancer is sarcoma, angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma, myxoma, rhabdomyoma, fibroma, lipoma, teratoma, bronchogenic carcinoma, squamous cell carcinoma, undifferentiated small cell carcinoma, undifferentiated large cell carcinoma, adenocarcinoma, alveolar (bronchiolar) carcinoma, bronchial adenoma, lymphoma, chondromatous hanlartoma, inesothelioma, leiomyosarcoma, carcinoma, ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors, vipoma, Karposi's sarcoma, leiomyoma, hemangioma, neurofibroma, tubular adenoma, villous adenoma, hamartoma, Wilm's tumor (nephroblastoma), leukemia, transitional cell carcinoma, seminoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, interstitial cell carcinoma, fibroadenoma, adenomatoid tumors, hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, hepatocellular adenoma, osteogenic sarcoma (osteosarcoma), malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochronfroma (osteocartilaginous exostoses), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma, giant cell tumors, osteoma, granuloma, xanthoma, osteitis defornians, meningioma, meningiosarcoma, gliomatosis, astrocytoma, medulloblastoma, glioma, ependymoma, germinoma (pinealoma), glioblastoma multiform, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors, spinal cord neurofibroma, meningioma, endometrial carcinoma, cervical carcinoma, pre-tumor cervical dysplasia, ovarian carcinoma, serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma, granulosa-thecal cell tumors, Sertoli-Leydig cell tumors, dysgerminoma, malignant teratoma, intraepithelial carcinoma, melanoma, clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma), fallopian tubes (carcinoma), myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative diseases, myelodysplastic syndrome, Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma), malignant melanoma, basal cell carcinoma, moles dysplastic nevi, dermatofibroma, keloids, psoriasis, or neuroblastoma.
46 . The method according to claim 40 , wherein R 1a is selected from —NO 2 , halogen, perfluoroalkyl, haloalkyl, and optionally substituted C 1-2 alkyl.
47 . The method according to claim 46 , wherein R 3 is selected from optionally substituted —O—C 1-4 alkyl, —O—C 1-4 perfluoro alkyl, optionally substituted —N(H)C 1-4 alkyl, optionally substituted —N(C 1-4 alkyl)C 1-4 alkyl, optionally substituted —S(O) 0-2 —C 1-4 alkyl, and optionally substituted —S(O) 0-2 —C 1-4 perfluoroalkyl.
48 . The method according to claim 47 , wherein Y is either —N(H)— or —C(R 6 )R 6 —.
49 . The method according to claim 48 , wherein X is selected from —O—, —N(R 5 )— and —S—.
50 . The method according to claim 49 , wherein Y is —C(R 6 )R 6 —; wherein each R 6 is independently selected from —H, halogen, trihalomethyl, —NH 2 , optionally substituted —O—C 1-4 alkyl, optionally substituted —N(H)C 1-4 alkyl, optionally substituted —S—C 1-4 alkyl, optionally substituted lower alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclylalkyl.
51 . The method according to claim 50 , wherein Y is —C(H)R 6 —; wherein R 6 is independently selected from —H, halogen, trihalomethyl, —NH 2 , optionally substituted —O—C 1-4 alkyl, optionally substituted —N(H)C 1-4 alkyl, optionally substituted —S—C 1-4 alkyl, optionally substituted lower alkyl, optionally substituted heterocyclyl, and optionally substituted heterocyclylalkyl.
52 . The method according to claim 51 , wherein Q is ═C(H)—.
53 . The method according to claim 37 , wherein the compound is selected from Table 3:
TABLE 3
Entry
Name
Structure
31
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [4-fluoro-3- (trifluoromethyl)phenyl]acetamide
34
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [4-chloro-3- (trifluoromethyl)phenyl]acetamide
55
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [2-chloro-5- (trifluoromethyl)phenyl]acetamide
62
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [2-amino-5- (trifluoromethyl)phenyl]acetamide
80
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[2- chloro-5-(trifluoromethyl)phenyl]-L- alaninamide
94
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- amino-5-(trifluoromethyl)phenyl]-L- alaninamide
112
methyl 3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoate
145
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoic acid
189
methyl 3-({N-[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoate
54 . The method according to claim 40 , wherein the compound is selected from Table 3:
TABLE 3
Entry
Name
Structure
31
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [4-fluoro-3- (trifluoromethyl)phenyl]acetamide
34
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [4-chloro-3- (trifluoromethyl)phenyl]acetamide
55
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [2-chloro-5- (trifluoromethyl)phenyl]acetamide
62
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [2-amino-5- (trifluoromethyl)phenyl]acetamide
80
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[2- chloro-5-(trifluoromethyl)phenyl]-L- alaninamide
94
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- amino-5-(trifluoromethyl)phenyl]-L- alaninamide
112
methyl 3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoate
145
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoic acid
189
methyl 3-({N-[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoate
55 . The method according to claim 42 , wherein the compound is selected from Table 3:
TABLE 3
Entry
Name
Structure
31
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [4-fluoro-3- (trifluoromethyl)phenyl]acetamide
34
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [4-chloro-3- (trifluoromethyl)phenyl]acetamide
55
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [2-chloro-5- (trifluoromethyl)phenyl]acetamide
62
2-{[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]thio}-N- [2-amino-5- (trifluoromethyl)phenyl]acetamide
80
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[2- chloro-5-(trifluoromethyl)phenyl]-L- alaninamide
94
N 2 -[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-N-[3- amino-5-(trifluoromethyl)phenyl]-L- alaninamide
112
methyl 3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoate
145
3-({N-[2-amino-5-cyano-6- (methylthio)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoic acid
189
methyl 3-({N-[2-amino-5-cyano-6- (methyloxy)pyrimidin-4-yl]-L- alanyl}amino)-5- (trifluoromethyl)benzoateJoin the waitlist — get patent alerts
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