INHIBITORS OF PROTEIN KINASES
Compounds that inhibit Aurora-kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.
1 . A compound having Formula I
or a therapeutically acceptable salt thereof, wherein
A 1 is C(O)NHR 1 , C(O)N(R 1 ) 2 , NHC(O)R 1 , NR 1 C(O)R 1 , NHC(O)NHR 1 , NHC(O)N(R 1 ) 2 , NR 1 C(O)NHR 1 , NR 1 C(O)N(R 1 ) 2 , SO 2 NHR 1 , SO 2 N(R 1 ) 2 , NHSO 2 R 1 , NR 1 SO 2 R 1 , OC(O)OR 1 , NHC(O)OR 1 , NR 1 C(O)OR 1 or R 5 ;
B 1 and C 1 are independently H, C(O)NHR 1 , C(O)N(R 1 ) 2 , NHC(O)R 1 , NR 1 C(O)R 1 , NHC(O)NHR 1 , NHC(O)N(R 1 ) 2 , NR 1 C(O)NHR 1 , NR 1 C(O)N(R 1 ) 2 , SO 2 NHR 1 , SO 2 N(R 1 ) 2 , NHSO 2 R 1 , NR 1 SO 2 R 1 , OC(O)OR 1 , NHC(O)OR 1 , NR 1 C(O)OR 1 or R 5 ; wherein
R 1 is R 2 , R 3 or R 4 ;
R 2 is phenyl which is unfused or fused with benzene, heteroarene or R 2A ; R 2A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 4 is heteroaryl which is unfused or fused with benzene, heteroarene or R 3A ; R 3A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 4 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R 4A ; R 4A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 5 is alkyl, alkenyl, or alkynyl, each of which is unsubstituted or substituted with one, two, three, four or five of independently selected R 6 , OR 6 , SR 6 , S(O)R 6 , SO 2 R 6 , NH 2 , NHR 6 , N(R 6 ) 2 , C(O)R 6 , C(O)NH 2 , C(O)NHR 6 , C(O)N(R 6 ) 2 , NHC(O)R 6 , NR 6 C(O)R 6 , NHSO 2 R 6 , NR 6 SO 2 R 6 , NHC(O)OR 6 , NR 6 C(O)OR 6 , SO 2 NH 2 , SO 2 NHR 6 , SO 2 N(R 6 ) 2 , NHC(O)NH 2 , NHC(O)R 6 , NHC(O)N(R 6 ) 2 , NR 6 C(O)N(R 6 ) 2 , OH, (O), C(O)OH, CN, CF 3 , OCF 3 , CF 2 CF 3 , F, Cl, Br or I;
R 6 is R 7 , R 8 , R 9 , or R 9A ;
R 7 is phenyl which is unfused or fused with benzene, heteroarene or R 7A ; R 7A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 8 is heteroaryl which is unfused or fused with benzene, heteroarene or R 8A ; R 8A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 9 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R 9A ; R 9A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 9A is alkyl, alkenyl, or alkynyl, each of which is unsubstituted or substituted with one, two, three, four or five of independently selected NH 2 , C(O)NH 2 , SO 2 NH 2 , NHC(O)NH 2 , OH, (O), C(O)OH, CN, CF 3 , OCF 3 , CF 2 CF 3 , F, Cl, Br or I;
wherein each foregoing cyclic moiety is independently unsubstituted or substituted with one or two or three or four or five of independently selected R 30 , OR 30 , OCH 2 R 30 , SR 30 , S(O)R 30 , SO 2 R 30 , C(O)R 30 , CO(O)R 30 , OC(O)R 30 , OC(O)OR 30 , NO 2 , NH 2 , NHR 30 , N(R 30 ) 2 , C(O)NH 2 , C(O)NHR 30 , C(O)N(R 30 ) 2 , NHC(O)R 30 , NHC(O)NHR 30 , NHC(O)N(R 30 ) 2 , NR 30 C(O)NHR 30 , NR 30 C(O)N(R 30 ) 2 , C(O)NHOH, C(O)NHOR 30 , C(O)NHSO 2 R 30 , C(O)NR 30 SO 2 R 30 , SO 2 NH 2 , SO 2 NHR 30 , SO 2 N(R 30 ) 2 , CF 3 , CF 2 CF 3 , C(O)H, C(O)OH, C(N)NH 2 , C(N)NHR 30 , C(N)N(R 30 ) 2 , CNOH, CNOCH 3 , OH, (O), N 3 , CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , F, Cl, Br or I;
R 30 is R 31 , R 32 , R 33 or R 34 ;
R 31 is phenyl which is unfused or fused with benzene, heteroarene or R 31A ; R 31A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 32 is heteroaryl which is unfused or fused with benzene, heteroarene or R 32A ; R 32A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 33 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R 33A ; R 33A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 34 is alkyl, alkenyl, or alkenyl, each of which is unsubstituted or substituted with one, two, three, four or five of independently selected R 35 , OR 35 , SR 35 , S(O)R 35 , SO 2 R 35 , NH 2 , NHR 35 , N(R 35 ) 2 , C(O)R 35 , C(O)NH 2 , C(O)NHR 35 , C(O)N(R 35 ) 2 , NHC(O)R 35 , NR 35 C(O)R 35 , NHSO 2 R 35 , NR 35 SO 2 R 35 , NHC(O)OR 35 , NR 35 C(O)OR 35 , SO 2 NH 2 , SO 2 NHR 35 , SO 2 N(R 35 ) 2 , NHC(O)NH 2 , NHC(O)NHR 35 , NHC(O)R 35 , NHC(O)N(R 35 ) 2 , NR 35 C(O)N(R 35 ) 2 , OH, (O), C(O)OH, CN, CF 3 , OCF 3 , CF 2 CF 3 , F, Cl, Br or I;
R 35 is R 36 , R 37 , R 38 or R 39 ;
R 36 is phenyl which is unfused or fused with benzene, heteroarene or R 36A ; R 36A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 37 is heteroaryl which is unfused or fused with benzene, heteroarene or R 37A ; R 37A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 38 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R 38A ; R 38A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 39 is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with R 40 ;
R 40 is phenyl, heteroaryl, cycloalkyl, cycloalkenyl or heterocycloalkyl;
wherein the moieties represented by R 31 , R 32 , R 33 R 36 , R 37 and R 38 are independently unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, OH, (O)OH, NO 2 , NH 2 , CF 3 , OH, R 45 , OR 45 , SR 45 , S(O)R 45 , SO 2 R 1 , C(O)NHR 45 , C(O)N(R 45 ) 2 , NHC(O)R 45 , NR 45 C(O)R 45 , NHC(O)NHR 45 , NHC(O)N(R 45 ) 2 , NR 45 C(O)NHR 45 , NR 45 C(O)N(R 45 ) 2 , SO 2 NHR 45 , SO 2 N(R 45 ) 2 , NHSO 2 R 45 , NR 1 SO 2 R 45 OC(O)OR 45 , NHC(O)OR 45 or NR 45 C(O)OR 45 ;
R 45 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected R 1 , F, Cl, Br, I, OH, C(O)OH, NO 2 or NH 2 ; and
R 50 is phenyl, heteroaryl, cycloalkyl, cycloalkenyl or heterocycloalkyl.
2 . The compound of claim 1 wherein
A 1 is C(O)NHR 1 , C(O)N(R 1 ) 2 , NHC(O)R 1 , NR 1 C(O)R 1 , NHC(O)NHR 1 , NHC(O)N(R 1 ) 2 , NR 1 C(O)NHR 1 , NR 1 C(O)N(R 1 ) 2 , SO 2 NHR 1 , SO 2 N(R 1 ) 2 , NHSO 2 R 1 , NR 1 SO 2 R 1 , OC(O)OR 1 , NHC(O)OR 1 , NR 1 C(O)OR 1 or R 5 ;
B 1 and C 1 are independently H, C(O)NHR 1 , C(O)N(R 1 ) 2 , NHC(O)R 1 , NR 1 C(O)R 1 , NHC(O)NHR 1 , NHC(O)N(R 1 ) 2 , NR 1 C(O)NHR 1 , NR 1 C(O)N(R 1 ) 2 , SO 2 NHR 1 , SO 2 N(R 1 ) 2 , NHSO 2 R 1 , NR 1 SO 2 R 1 , OC(O)OR 1 , NHC(O)OR 1 , NR 1 C(O)OR 1 or R 5 ; wherein
R 1 is R 2 , R 3 or R 4 ;
R 2 is phenyl which is unfused or fused with benzene, heteroarene or R 2A ; R 2A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 3 is heteroaryl which is unfused or fused with benzene, heteroarene or R 3A ; R 3A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 4 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R 4A ; R 4A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 5 is alkyl, alkenyl, or alkynyl, each of which is unsubstituted or substituted with one, two, three, four or five of independently selected R 6 , OR 6 , SR 6 , S(O)R 6 , SO 2 R 6 , NH 2 , NHR 6 , N(R 6 ) 2 , C(O)R 6 , C(O)NH 2 , C(O)NHR 6 , C(O)N(R 6 ) 2 , NHC(O)R 6 , NR 6 C(O)R 6 , NHSO 2 R 6 , NR 6 SO 2 R 6 , NHC(O)OR 6 , NR 6 C(O)OR 6 , SO 2 NH 2 , SO 2 NHR 6 , SO 2 N(R 6 ) 2 , NHC(O)NH 2 , NHC(O)R 6 , NHC(O)N(R 6 ) 2 , NR 6 C(O)N(R 6 ) 2 , OH, (O), C(O)OH, CN, CF 3 , OCF 3 , CF 2 CF 3 , F, Cl, Br or I;
R 6 is R 7 , R 8 , R 9 , or R 9A ;
R 7 is phenyl which is unfused or fused with benzene, heteroarene or R 7A ; R 7A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 8 is heteroaryl which is unfused or fused with benzene, heteroarene or R 8A ; R 8A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 9 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R 9A ; R 9A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 9A is alkyl, alkenyl, or alkynyl, each of which is unsubstituted or substituted with one, two, three, four or five of independently selected NH 2 , C(O)NH 2 , SO 2 NH 2 , NHC(O)NH 2 , OH, (O), C(O)OH, CN, CF 3 , OCF 3 , CF 2 CF 3 , F, Cl, Br or I;
wherein each foregoing cyclic moiety is independently unsubstituted or substituted with one or two or three or four or five of independently selected R 30 , NHC(O)R 30 NHC(O)NHR 30 , F, Cl, Br or I;
R 30 is R 31 , R 32 , R 33 or R 34 ;
R 31 is phenyl which is unfused or fused with benzene, heteroarene or R 31A ; R 31A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 32 is heteroaryl which is unfused or fused with benzene, heteroarene or R 32A ; R 32A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 33 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R 33A ; R 33A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 34 is alkyl, alkenyl, or alkenyl, each of which is unsubstituted or substituted with one, two, three, four or five of independently selected R 35 , OR 35 , SR 35 , S(O)R 35 , SO 2 R 35 , NH 2 , NHR 35 , N(R 35 ) 2 , C(O)R 35 , C(O)NH 2 , C(O)NHR 35 , C(O)N(R 35 ) 2 , NHC(O)R 35 , NR 35 C(O)R 35 , NHSO 2 R 35 , NR 35 SO 2 R 35 , NHC(O)OR 35 , NR 35 C(O)OR 35 , SO 2 NH 2 , SO 2 NHR 35 , SO 2 N(R 35 ) 2 , NHC(O)NH 2 , NHC(O)NHR 35 , NHC(O)R 35 , NHC(O)N(R 35 ) 2 , NR 35 C(O)N(R 35 ) 2 , OH, (O), C(O)OH, CN, CF 3 , OCF 3 , CF 2 CF 3 , F, Cl, Br or I;
R 35 is R 36 , R 37 , R 38 or R 39 ;
R 36 is phenyl which is unfused or fused with benzene, heteroarene or R 36A ; R 36A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 37 is heteroaryl which is unfused or fused with benzene, heteroarene or R 37A ; R 37A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 38 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is unfused or fused with benzene, heteroarene or R 38A ; R 38A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene;
R 39 is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with R 40 ;
R 40 is phenyl, heteroaryl, cycloalkyl, cycloalkenyl or heterocycloalkyl;
wherein the moieties represented by R 31 , R 32 , R 33 R 36 , R 37 and R 38 are independently unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, CF 3 , R 45 ; and
R 45 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, OH, C(O)OH, NO 2 or NH 2 .
3 . The compound of claim 2 wherein
A 1 is C(O)NHR 1 , C(O)N(R 1 ) 2 , NHC(O)R 1 , NR 1 C(O)R 1 , NHC(O)NHR 1 , NHC(O)N(R 1 ) 2 , NR 1 C(O)NHR 1 , NR 1 C(O)N(R 1 ) 2 , SO 2 NHR 1 , SO 2 N(R 1 ) 2 , NHSO 2 R 1 , NR 1 SO 2 R 1 , OC(O)OR 1 , NHC(O)OR 1 , NR 1 C(O)OR 1 or R 5 ;
B 1 and C 1 are independently H, C(O)NHR 1 , C(O)N(R 1 ) 2 , NHC(O)R 1 , NR 1 C(O)R 1 , NHC(O)NHR 1 , NHC(O)N(R 1 ) 2 , NR 1 C(O)NHR 1 , NR 1 C(O)N(R 1 ) 2 , SO 2 NHR 1 , SO 2 N(R 1 ) 2 , NHSO 2 R 1 , NR 1 SO 2 R 1 , OC(O)OR 1 , NHC(O)OR 1 , NR 1 C(O)OR 1 or R 5 ; wherein
R 1 is R 2 , R 3 or R 4 ;
R 2 is phenyl;
R 3 is heteroaryl;
R 4 is cycloalkyl;
R 5 is alkyl, alkenyl, or alkynyl, each of which is unsubstituted or substituted with one, two, three, four or five of independently selected R 6 , OR 6 , SR 6 , S(O)R 6 , SO 2 R 6 , NH 2 , NHR 6 , N(R 6 ) 2 , C(O)R 6 , C(O)NH 2 , C(O)NHR 6 , C(O)N(R 6 ) 2 , NHC(O)R 6 , NR 6 C(O)R 6 , NHSO 2 R 6 , NR 6 SO 2 R 6 , NHC(O)OR 6 , NR 6 C(O)OR 6 , SO 2 NH 2 , SO 2 NHR 6 , SO 2 N(R 6 ) 2 , NHC(O)NH 2 , NHC(O)R 6 , NHC(O)N(R 6 ) 2 , NR 6 C(O)N(R 6 ) 2 , OH, (O), C(O)OH, CN, CF 3 , OCF 3 , CF 2 CF 3 , F, Cl, Br or I;
R 6 is R 7 , R 8 , R 9 , or R 9A ;
R 7 is phenyl;
R 8 is heteroaryl;
R 9 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl;
R 9A is alkyl, alkenyl, or alkynyl, each of which is unsubstituted or substituted with one, two, three, four or five of independently selected NH 2 , C(O)NH 2 , SO 2 NH 2 , NHC(O)NH 2 , OH, (O), C(O)OH, CN, CF 3 , OCF 3 , CF 2 CF 3 , F, Cl, Br or I;
wherein each foregoing cyclic moiety is independently unsubstituted or substituted with one or two or three or four or five of independently selected R 30 , NHC(O)R 30 NHC(O)NHR 30 , F, Cl, Br or I;
R 30 is R 31 , R 32 , R 33 or R 34 ;
R 31 is phenyl;
R 32 is heteroaryl;
R 33 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl;
R 34 is alkyl, alkenyl, or alkenyl, each of which is unsubstituted or substituted with one, two, three, four or five of independently selected R 35 , OR 35 , SR 35 , S(O)R 35 , SO 2 R 35 NH 2 , NHR 35 , N(R 35 ) 2 , C(O)R 35 , C(O)NH 2 , C(O)NHR 35 , C(O)N(R 35 ) 2 , NHC(O)R 35 NR 35 C(O)R 35 , NHSO 2 R 35 , NR 35 SO 2 R 35 , NHC(O)OR 35 , NR 35 C(O)OR 35 , S 2 NH 2 , SO 2 NHR 35 , SO 2 N(R 35 ) 2 , NHC(O)NH 2 , NHC(O)NHR 35 , NHC(O)R 35 , NHC(O)N(R 35 ) 2 , NR 35 C(O)N(R 35 ) 2 , OH, (O), C(O)OH, CN, CF 3 , OCF 3 , CF 2 CF 3 , F, Cl, Br or I;
R 35 is R 36 , R 37 , R 38 or R 39 ;
R 36 is phenyl;
R 37 is heteroaryl;
R 38 is cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl;
R 39 is alkyl, alkenyl or alkenyl, each of which is unsubstituted or substituted with R 40 ;
R 40 is phenyl, heteroaryl, cycloalkyl, cycloalkenyl or heterocycloalkyl;
wherein the moieties represented by R 31 , R 32 , R 33 R 36 , R 37 and R 38 are independently unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, CF 3 , R 45 ; and
R 45 is alkyl, alkenyl or alkynyl, each of which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, OH, C(O)OH, NO 2 or NH 2 .
4 . The compound of claim 3 wherein
A 1 is C(O)NHR 1 ;
B 1 and C 1 are independently H or R 1 ; wherein
R 1 is R 2 or R 4 ;
R 2 is phenyl;
R 4 is cycloalkyl;
R 5 is alkyl, each of which is unsubstituted or substituted with C(O)NHR 6 , F, Cl, Br or I;
R 6 is R 9A ;
R 9A is alkyl, which is unsubstituted or substituted with OH, F, Cl, Br or I;
wherein each foregoing cyclic moiety is independently unsubstituted or substituted with one or two or three or four or five of independently selected R 30 , NHC(O)R 30 NHC(O)NHR 30 , F, Cl, Br or I;
R 30 is R 31 , R 32 , or R 34 ;
R 31 is phenyl;
R 32 is heteroaryl;
R 34 is alkyl, each of which is unsubstituted or substituted with NHSO 2 R 35 , NHC(O)NHR 35 , F, Cl, Br, or I;
R 35 is R 36 , or R 37 ;
R 36 is phenyl;
R 37 is heteroaryl;
wherein the moieties represented by R 31 and R 36 are independently unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, CF 3 , R 45 ; and
R 45 is alkyl, which is unsubstituted or substituted with one or two or three of independently selected F, Cl, Br, I, or OH.
5 . A compound of claim 4 , which is
8-amino-N-(4-((((3-fluorophenyl)amino)carbonyl)amino)phenyl)-3-methylimidazo[1,5-a]pyrazine-1-carboxamide,
8-amino-N-(4-((anilinocarbonyl)amino)phenyl)-3-methylimidazo[1,5-a]pyrazine-1-carboxamide,
8-amino-N-(4-(benzoylamino)phenyl)-3-methylimidazo[1,5-a]pyrazine-1-carboxamide,
8-amino-3-methyl-N-(4-((((3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide,
8-amino-N-(3-(((((3-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-3-methylimidazo[1,5-a]pyrazine-1-carboxamide,
8-amino-N-(3-(((anilinocarbonyl)amino)methyl)phenyl)-3-methylimidazo[1,5-a]pyrazine-1-carboxamide,
8-amino-N-(3-(((((2-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-3-methylimidazo[1,5-a]pyrazine-1-carboxamide,
8-amino-N-(3-(((((4-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-3-methylimidazo[1,5-a]pyrazine-1-carboxamide,
8-amino-3-methyl-N-(3-(((((4-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide,
8-amino-N-(4-((((3-(2-hydroxyethyl)phenyl)amino)carbonyl)amino)phenyl)-3-methylimidazo[1,5-a]pyrazine-1-carboxamide,
8-amino-N-(4-((((4-(2-hydroxyethyl)phenyl)amino)carbonyl)amino)phenyl)-3-methylimidazo[1,5-a]pyrazine-1-carboxamide
8-amino-3-cyclopropyl-N-(4-((((3-fluorophenyl)amino)carbonyl)amino)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-N-(4-((anilinocarbonyl)amino)phenyl)-3-cyclopropylimidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(4-((((3-methylphenyl)amino)carbonyl)amino)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(4-((((2-fluoro-5-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(4-((((4-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(3-((((pyridin-3-ylamino)carbonyl)amino)methyl)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(4-((((3-fluorophenyl)amino)carbonyl)amino)-3-methylphenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(4-((((2-fluorophenyl)amino)carbonyl)amino)-3-methylphenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(3-methyl-4-((((4-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(3-((((3-fluorophenyl)amino)carbonyl)amino)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(3-(((((3-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-N-(3-(((((4-chloro-2-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-3-cyclopropylimidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-N-(3-(((anilinocarbonyl)amino)methyl)phenyl)-3-cyclopropylimidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(3-(((((3,4-difluorophenyl)amino)carbonyl)amino)methyl)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(3-(((((2-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(3-(((((4-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-N-(3-(((((3-chlorophenyl)amino)carbonyl)amino)methyl)phenyl)-3-cyclopropylimidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-N-(3-(((((4-chlorophenyl)amino)carbonyl)amino)methyl)phenyl)-3-cyclopropylimidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(4-(((pyridin-3-ylamino)carbonyl)amino)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(3-(((phenylsulfonyl)amino)methyl)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-(3-(ethyl(2-hydroxyethyl)amino)-3-oxopropyl)-N-(3-(((((4-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-N-(3-(((((4-chloro-2-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)-3-(3-(ethyl(2-hydroxyethyl)amino)-3-oxopropyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-(3-(ethyl(2-hydroxyethyl)amino)-3-oxopropyl)-N-(3-(((((3-fluorophenyl)amino)carbonyl)amino)methyl)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-(3-(ethyl(2-hydroxyethyl)amino)-3-oxopropyl)-N-(4-((((3-fluorophenyl)amino)carbonyl)amino)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
8-amino-3-cyclopropyl-N-(3-(((((4-(trifluoromethyl)phenyl)amino)carbonyl)amino)methyl)phenyl)imidazo[1,5-a]pyrazine-1-carboxamide;
or a therapeutically acceptable salt thereof.
6 . A composition comprising an excipient and a therapeutically effective amount of a compound having Formula I.
7 . A method of treating bladder cancer, breast cancer, cervical cancer, colon cancer, endometrial cancer, esophageal cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, skin cancer, stomach cancer or thyroid cancer in a mammal, the method comprising administering thereto a therapeutically effective amount of a compound having Formula I.