Sulfoximine-substituted pyrimidines as CDK- and/or VEGF inhibitors, their production and use as pharmaceutical agents
View Patent ↗This invention relates to pyrimidine derivatives of general formula I in which Q, R 1 , R 2 , R 3 , R 4 , R 5 , X, and m have the meanings that are contained in the description, as inhibitors of cyclin-dependent kinases and VEGF-receptor tyrosine kinases, their production as well as their use as medications for treatment of various diseases.
1. Compounds of general formula (I)
in which
Q stands for the group
[or]
D, E, G,
L, M and T, in each case independently of one another, stand for carbon, oxygen, nitrogen or sulfur,
R 1 stands for hydrogen, halogen, C 1 -C 6 -alkyl, CF 3 , CN, nitro, or for the group —COR 8 or —O—C 1 -C 6 -alkyl,
R 2 stands for hydrogen, or C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl, C 2 -C 10 -alkinyl, C 3 -C 10 -cycloalkyl, aryl or heteroaryl that is optionally substituted in one or more places, in the same way or differently, with hydroxy, halogen, C 1 -C 6 -alkoxy, amino, cyano, C 1 -C 6 -alkyl, —NH—(CH 2 ) n —C 3 -C 10 -cycloalkyl, —C 3 -C 10 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkinyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, —NHC 1 -C 6 -alkyl, —N(C 1 -C 6 -alkyl) 2 , C 1 -C 6 -alkanoyl, —CONR 9 R 10 , —COR 8 , C 1 -C 6 -alkylOAc, aryl, heteroaryl, —(CH 2 ) n -aryl, —(CH 2 ) n -heteroaryl, phenyl-(CH 2 ) n —R 8 , —(CH 2 ) n PO 3 (R 8 ) 2 or with the group —R 6 or —NR 9 R 10 , and the phenyl, C 3 -C 10 -cycloalkyl, aryl, heteroaryl, —(CH 2 ) n -aryl and —(CH2) n -heteroaryl itself optionally can be substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, or with the group —CF 3 or —OCF 3 , and the ring of C 3 -C 10 -cycloalkyl and C 1 -C 10 -alkyl optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or can be interrupted by one or more —C(O) groups in the ring and/or optionally one or more possible double bonds can be contained in the ring,
X stands for oxygen, sulfur, or for the group —NH— or —N(C 1 -C 3 -alkyl)-
or
X and R 2 together form a C 3 -C 10 -cycloalkyl ring, which optionally can contain one or more heteroatoms and optionally can be substituted in one or more places, in the same way or differently, with hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, halogen or the group —NR 9 R 10 ,
R 3 stands for hydrogen, hydroxy, halogen, CF 3 , OCF 3 or for the group —NR 9 R 10 , or for C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl or C 1 -C 6 -alkoxy that is optionally substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 1 -C 6 -alkoxy or the group —NR 9 R 10 ,
m stands for 0-4,
R 4 stands for hydrogen or for the group —COR 8 , NO 2 , trimethylsilanyl (TMS), tert-butyl-dimethylsilanyl (TBDMS), tert-butyl-diphenylsilanyl (TBDPS), triethylsilanyl (TES) or —SO 2 R 7 or for C 1 -C 10 -alkyl or C 3 -C 10 -cycloalkyl that is optionally substituted in one or more places, in the same way or differently, with hydroxy, halogen, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, cyano, C 3 -C 10 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkinyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl or with the group —CONR 9 R 10 , COR 8 , —CF 3 , —OCF 3 or —NR 9 R 10 ,
R 5 stands for C 1 -C 10 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkinyl or C 3 -C 10 -cycloalkyl that is optionally substituted in one or more places, in the same way or differently, with hydroxy, C 1 -C 6 -alkoxy, C 3 -C 10 -cycloalkyl, halogen or the group —NR 9 R 10 ,
or
R 4 and R 5 together can form a C 5 -C 10 -cycloalkyl ring of group
whereby
V, W and Y, in each case independently of one another, stand for —CH 2 — that is optionally substituted in one or more places, in the same way or differently, with hydroxy, C 1 -C 10 -alkyl, C 1 -C 10 -alkoxy or —NR 9 R 10 , whereby C 1 -C 10 -alkyl or C 1 -C 10 -alkoxy also can be substituted in one or more places, in the same way or differently, with hydroxy, —NR 9 R 10 or C 1 -C 10 -alkoxy and/or can be interrupted by one or more —C(O)— groups in the ring, and/or optionally one or more double bonds can be contained in the ring,
R 6 stands for a heteroaryl or a C 3 -C 10 -cycloalkyl ring, which optionally can contain one or more heteroatoms and optionally can be substituted in one or more places, in the same way or differently, with hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or halogen,
R 7 stands for C 1 -C 10 -alkyl or aryl that is optionally substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or with the group trimethylsilanyl (TMS) or —NR 9 R 10 ,
R 8 stands for hydrogen, C 1 -C 6 -alkyl, hydroxy, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, benzoxy or —NR 9 R 10 ,
R 9 and R 10 , in each case independently of one another, stand for hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, hydroxy, hydroxy-C 1 -C 6 -alkyl, dihydroxy-C 1 -C 6 -alkyl, phenyl, heteroaryl or for the group —(CH 2 ) n NR 9 R 10 , —CNHNH 2 or —NR 9 R 10 ,
or
R 9 and R 10 together form a C 3 -C 10 -cycloalkyl ring that optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or can be interrupted by one or more —C(O)— groups in the ring and/or optionally one or more possible double bonds can be contained in the ring, and
n stands for 1-6,
as well as their isomers, diastereomers, enantiomers and/or salts.
2. Compounds of general formula (I) according to claim 1 , in which
Q stands for aryl,
R 1 stands for hydrogen, halogen, C 1 -C 6 -alkyl, CF 3 , CN, nitro, or for the group —COR 8 or —O—C 1 -C 6 -alkyl,
R 2 stands for hydrogen or C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl, C 2 -C 10 -alkinyl, C 3 -C 10 -cycloalkyl, aryl or heteroaryl that is optionally substituted in one or more places, in the same way or differently, with hydroxy, halogen, C 1 -C 6 -alkoxy, amino, cyano, C 1 -C 6 -alkyl, —NH—(CH 2 ) n —C 3 -C 10 -cycloalkyl, —C 3 -C 10 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkinyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, —NHC 1 -C 6 -alkyl, —N(C 1 -C 6 -alkyl) 2 , C 1 -C 6 -alkanoyl, —CONR 9 R 10 , —COR 8 , C 1 -C 6 -alkylOAc, aryl, heteroaryl, —(CH 2 ) n -aryl, —(CH 2 ) n -heteroaryl, phenyl-(CH 2 ) n —R 8 , —(CH 2 ) n PO 3 (R 8 ) 2 or with the group —R 6 or —NR 9 R 10 , and the phenyl, C 3 -C 10 -cycloalkyl, aryl, heteroaryl, —(CH 2 ) n -aryl and —(CH 2 ) n -heteroaryl itself optionally can be substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or with the group —CF 3 or —OCF 3 , and the ring of the C 3 -C 10 -cycloalkyl and the C 1 -C 10 -alkyl optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or can be interrupted by one or more —C(O)— groups in the ring and/or optionally one or more possible double bonds can be contained in the ring,
X stands for oxygen, sulfur, or for the group —NH—, or —N(C 1 -C 3 -alkyl)-
or
X and R 2 together form a C 3 -C 10 -cycloalkyl ring, which optionally can contain one or more heteroatoms and optionally can be substituted in one or more places, in the same way or differently, with hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, halogen or the group —NR 9 R 10 ,
R 3 stands for hydrogen, hydroxy, halogen, CF 3 , OCF 3 or for the group —NR 9 R 10 , or for C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl or C 1 -C 6 -alkoxy that is optionally substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 1 -C 6 -alkoxy or the group —NR 9 R 10 ,
m stands for 0-4,
R 4 stands for hydrogen or for the group —COR 8 , NO 2 , trimethylsilanyl (TMS), tert-butyl-dimethylsilanyl (TBDMS), tert-butyl-diphenylsilanyl (TBDPS), triethylsilanyl (TES) or for —SO 2 R 7 or for C 1 -C 10 -alkyl or C 3 -C 10 -cycloalkyl that is optionally substituted in one or more places, in the same way or differently, with hydroxy, halogen, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, cyano, C 3 -C 10 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkinyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl or with the group —CONR 9 R 10 , COR 8 , —CF 3 , —OCF 3 or —NR 9 R 10 ,
R 5 stands for C 1 -C 10 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkinyl or C 3 -C 10 -cycloalkyl that is optionally substituted in one or more places, in the same way or differently, with hydroxy, C 1 -C 6 -alkoxy, C 3 -C 10 -cycloalkyl, halogen, or the group —NR 9 R 10 ,
or
R 4 and R 5 together can form a C 5 -C 10 -cycloalkyl ring of the group
whereby
V, W and Y, in each case, independently of one another, stands for —CH 2 —, which is optionally substituted in one or more places, in the same way or differently, with hydroxy, C 1 -C 10 -alkyl, C 1 -C 10 -alkoxy or —NR 9 R 10 , whereby C 1 -C 10 -alkyl or C 1 -C 10 -alkoxy also can be substituted in one or more places, in the same way or differently, with hydroxy, —NR 9 R 10 or C 1 -C 10 -alkoxy and/or can be interrupted by one or more —C(O)— groups in the ring, and/or optionally one or more double bonds can be contained in the ring,
R 6 stands for a heteroaryl or a C 3 -C 10 -cycloalkyl ring, which optionally can contain one or more heteroatoms and optionally can be substituted in one or more places, in the same way or differently, with hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or halogen,
R 7 stands for C 1 -C 10 -alkyl or aryl that is optionally substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 1 -C 6 -alkyl, or C 1 -C 6 -alkoxy or with the group trimethylsilanyl (TMS) or —NR 9 R 10 ,
R 8 stands for hydrogen, C 1 -C 6 -alkyl, hydroxy, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, benzoxy or —NR 9 R 10 ,
R 9 and R 10 , in each case independently of one another, stand for hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, hydroxy, hydroxy-C 1 -C 6 -alkyl, dihydroxy-C 1 -C 6 -alkyl, phenyl, heteroaryl, or for the group —(CH 2 ) n NR 9 R 10 , —CNHNH 2 or —NR 9 R 10 ,
or
R 9 and R 10 together form a C 3 -C 10 -cycloalkyl ring that optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or can be interrupted by one or more —C(O)— groups in the ring and/or optionally one or more possible double bonds can be contained in the ring, and
n stands for 1-6,
as well as their isomers, diastereomers, enantiomers and/or salts.
3. Compounds of general formula (I) according to claim 1 , in which
Q stands for phenyl,
R 1 stands for hydrogen, halogen, C 1 -C 6 -alkyl, CF 3 , CN, nitro or for the group —COR 8 or —O—C 1 -C 6 -alkyl,
R 2 stands for hydrogen or for C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl, C 2 -C 10 -alkinyl, C 3 -C 10 -cycloalkyl, aryl or heteroaryl that is optionally substituted in one or more places, in the same way or differently, with hydroxy, halogen, C 1 -C 6 -alkoxy, amino, cyano, C 1 -C 6 -alkyl, —NH—(CH 2 ) n —C 3 -C 10 -cycloalkyl, —C 3 -C 10 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkinyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, —NHC 1 -C 6 -alkyl, —N(C 1 -C 6 -alkyl) 2 , C 1 -C 6 -alkanoyl, —CONR 9 R 10 , —COR 8 , C 1 -C 6 -alkylOAc, aryl, heteroaryl, —(CH 2 ) n -aryl, —(CH 2 ) n -heteroaryl, phenyl-(CH 2 ) n —R 8 , —(CH 2 ) n PO 3 (R 8 ) 2 or with the group —R 6 or —NR 9 R 10 , and phenyl, C 3 -C 10 -cycloalkyl, aryl, heteroaryl, —(CH 2 ) n -aryl and —(CH 2 ) n -heteroaryl itself optionally can be substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, or with the group —CF 3 or —OCF 3 , and the ring of C 3 -C 10 -cycloalkyl and C 1 -C 10 -alkyl optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms, and/or can be interrupted by one or more —C(O)— groups in the ring, and/or optionally one or more possible double bonds can be contained in the ring,
X stands for oxygen, sulfur, or for the group —NH— or —N(C 1 -C 3 -alkyl)-,
or
X and R 2 together form a C 3 -C 10 -cycloalkyl ring, which optionally can contain one or more heteroatoms, and optionally can be substituted in one or more places with hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, halogen or the group —NR 9 R 10 ,
R 3 stands for hydrogen, hydroxy, halogen, CF 3 , OCF 3 or for the group —NR 9 R 10 or for C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl or C 1 -C 6 -alkoxy that is optionally substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 1 -C 6 -alkoxy or the group —NR 9 R 10 ,
m stands for 0-2,
R 4 stands for hydrogen or for the group —COR 8 , NO 2 , trimethylsilanyl (TMS), tert-butyl-dimethylsilanyl (TBDMS), tert-butyl-diphenylsilanyl (TBDPS), triethylsilanyl (TES) or —SO 2 R 7 , or for C 1 -C 10 -alkyl or C 3 -C 10 -cycloalkyl that is optionally substituted in one or more places, in the same way or differently, with hydroxy, halogen, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, cyano, C 3 -C 10 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkinyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl or with the group —CONR 9 R 10 , COR 8 , —CF 3 , —OCF 3 or —NR 9 R 10 ,
R 5 stands for C 1 -C 10 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkinyl or C 3 -C 10 -cycloalkyl that is optionally substituted in one or more places, in the same way or differently, with hydroxy, C 1 -C 6 -alkoxy, C 3 -C 10 -cycloalkyl, halogen or the group —NR 9 R 10 ,
or
R 4 and R 5 together can form a C 5 -C 10 -cycloalkyl ring of the group
whereby
V, W, and Y, in each case independently of one another, stand for —CH 2 — that is optionally substituted in one or more places, in the same way or differently, with hydroxy, C 1 -C 10 -alkyl, C 1 -C 10 -alkoxy or —NR 9 R 10 , whereby C 1 -C 10 -alkyl or C 1 -C 10 -alkoxy also can be substituted in one or more places, in the same way or differently, with hydroxy, —NR 9 R 10 or C 1 -C 10 -alkoxy, and/or can be interrupted by one or more —C(O)— groups in the ring, and/or optionally one or more double bonds can be contained in the ring,
R 6 stands for a heteroaryl or a C 3 -C 10 -cycloalkyl ring, which optionally can contain one or more heteroatoms, and optionally can be substituted in one or more places, in the same way or differently, with hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or halogen,
R 7 stands for C 3 -C 10 -aryl or aryl that is optionally substituted in one or more places, in the same way or differently, with halogen, hydroxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or with the group trimethylsilanyl (TMS) or —NR 9 R 10 ,
R 8 stands for hydrogen, C 1 -C 6 -alkyl, hydroxy, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, benzoxy or —NR 9 R 10 ,
R 9 and R 10 , in each case independently of one another, stand for hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, hydroxy, hydroxy-C 1 -C 6 -alkyl, dihydroxy-C 1 -C 6 -alkyl, phenyl, heteroaryl or for the group —(CH 2 ) n NR 9 R 10 , —CNHNH 2 or —NR 9 R 10 ,
or
R 9 and R 10 together form a C 3 -C 10 -cycloalkyl ring, which optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and/or can be interrupted by one or more —C(O)— groups in the ring and/or optionally one or more possible double bonds can be contained in the ring, and
n stands for 1-6,
as well as their isomers, diastereomers, enantiomers and/or salts.
4. Compounds of general formula (I) according to claim 1 , in which
Q stands for phenyl,
R 1 stands for hydrogen, halogen, CN, NO 2 or CF 3 ,
R 2 stands for C 1 -C 10 -alkyl, C 2 -C 10 -alkinyl, aryl or heteroaryl that is optionally substituted in one or more places, in the same way or differently, with hydroxy, halogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkinyl or with the group —COR 8 ,
X stands for oxygen, sulfur or for the group —NH—,
R 3 stands for hydrogen, halogen, hydroxy or C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy that is optionally substituted in one or more places with halogen or hydroxy,
m stands for 0-2,
R 4 stands for hydrogen or for the group NO 2 , —CO—R 8 , —SO 2 R 7 or for C 1 -C 10 -alkyl that is optionally substituted in one or more places, in the same way or differently, with halogen or hydroxy,
R 5 stands for C 1 -C 10 -alkyl or C 3 -C 10 -cycloalkyl that is optionally substituted in one or more places, in the same way or differently, with hydroxy or C 3 -C 10 -cycloalkyl,
or
R 4 and R 5 together can form a C 5 -C 10 -cycloalkyl ring of the group
whereby
V, W and Y, in each case independently of one another, stand for —CH 2 — that is optionally substituted in one or more places, in the same way or differently, with hydroxy, C 1 -C 10 -alkyl, C 1 -C 10 -alkoxy or —NR 9 R 10 , whereby C 1 -C 10 -alkyl or C 1 -C 10 -alkoxy also can be substituted in one or more places, in the same way or differently, with hydroxy, —NR 9 R 10 or C 1 -C 10 -alkoxy and/or can be interrupted by one or more —C(O)— groups in the ring and/or optionally one or more double bonds can be contained in the ring,
R 7 stands for C 1 -C 10 -alkyl that is optionally substituted in one or more places in the same way or differently, with the group trimethylsilanyl (TMS),
R 8 stands for hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or C 3 -C 6 -cycloalkyl, which optionally can be substituted in one or more places with C 1 -C 6 -alkyl,
n stands for 1,
as well as their isomers, diastereomers, enantiomers and/or salts.
5. Compounds of general formula (I) according to claim 1 , in which
Q stands for phenyl,
R 1 stands for hydrogen or halogen,
R 2 stands for C 1 -C 10 -alkyl, C 2 -C 10 -alkinyl or aryl that is optionally substituted in one or more places, in the same way or differently, with hydroxy, halogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 2 -C 6 -alkinyl or with the group —COR 8 ,
X stands for oxygen, sulfur or for the group —NH—,
R 3 stands for hydrogen, halogen or C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy that is optionally substituted in one or more places with halogen,
m stands for 0-2,
R 4 stands for hydrogen or for the group NO 2 , —SO 2 R 7 or for C 1 -C 10 -alkyl,
R 5 stands for C 1 -C 10 -alkyl or C 3 -C 10 -cycloalkyl that is optionally substituted in one or more places, in the same way or differently, with hydroxy or C 3 -C 10 -cycloalkyl,
R 7 stands for C 1 -C 10 -alkyl that is optionally substituted in one or more places in the same way or differently, with the group trimethylsilanyl (TMS),
R 8 stands for hydrogen, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or C 3 -C 6 -cycloalkyl, which optionally can be substituted in one or more places with C 1 -C 6 -alkyl,
as well as their isomers, diastereomers, enantiomers and/or salts.
6. Compounds of general formula (I) according to claim 1 , in which
Q stands for phenyl,
R 1 stands for hydrogen or halogen,
R 2 stands for C 1 -C 10 -alkyl, C 2 -C 10 -alkinyl or aryl that is optionally substituted in one or more places, in the same way or differently, with hydroxy, halogen, methyl, methoxy, ethinyl or with the group —COH or —COCH 3 ,
X stands for oxygen, sulfur or for the group —NH—,
R 3 stands for hydrogen, halogen, methyl, methoxy or —CF 3 ,
m stands for 0-2,
R 4 stands for hydrogen, methyl or for the group NO 2 , —COOC 2 H 5 or —SO 2 C 2 H 4 —Si(CH 3 ) 3 ,
R 5 stands for methyl, ethyl, cyclopropyl, cyclopentyl, —(CH 2 )-cyclopropyl or hydroxyethyl,
as well as their isomers, diastereomers, enantiomers and/or salts.
7. In the method for preparing a compound of formula (I) according to claim 1 , wherein the improvement is the use of a compound of general formula (IIa) or (IIb)
in which Z stands for —NH 2 or NO 2 , and m, R 3 , R 4 and R 5 have the meanings that are indicated in general formula (I), as well as their isomers, diastereomers, enantiomers and/or salts as intermediate products for the production of the compound of general formula (I).
8. A method according to claim 7 , characterized in that
m stands for 0-2,
R 3 stands for halogen, or for C 1 -C 10 -alkyl or C 1 -C 10 -alkoxy that is optionally substituted in one or more places with halogen,
R 4 stands for hydrogen or for the group NO 2 , —SO 2 —R 7 , —CO—R 8 or for C 1 -C 10 -alkyl, whereby R 7 and R 8 have the meaning that is indicated in general formula (I), and R 5 stands for C 1 -C 10 -alkyl or C 3 -C 6 -cycloalkyl that is optionally substituted in one or more places with halogen or hydroxy.
9. In a method for preparing a compound of formula (I) according to claim 1 , wherein the improvement is the use of a compound of general formula (IIIa), (IIIb) or (IIIc),
in which W stands for halogen, hydroxy or X—R 2 , and R 1 , R 2 , R 3 , R 5 , m and X have the meanings that are indicated in general formula (I), as well as their isomers, diastereomers, enantiomers, and/or salts as intermediate products for the production of the compound of general formula (I).
10. A method according to claim 9 , wherein
R 1 stands for halogen,
X stands for —NH—,
R 2 stands for C 1 -C 10 -alkyl that is optionally substituted in one or more places with hydroxy,
m stands for 0, and
R 5 stands for C 1 -C 10 -alkyl.
11. In a method for preparing a compound of formula (I) according to claim 1 , wherein the improvement is the use of a compounds of general formula (IV),
in which
Hal stands for halogen, Y stands for halogen, hydroxy or X—R 2 , and R 1 , R 2 and X have the meanings that are indicated in general formula (I), as well as their isomers, diastereomers, enantiomers and/or salts as intermediate products for the production of the compound of general formula (I).
12. A method according to claim 11 , in which
X stands for oxygen, sulfur or —NH—,
R 1 stands for halogen,
R 2 stands for C 1 -C 10 -alkyl or C 2 -C 10 -alkinyl that is optionally substituted with hydroxy, C 1 -C 6 -alkoxy or with the group —CO—R 8 , whereby R 8 has the meaning that is indicated in general formula (I).
13. Pharmaceutical agent that comprises a compound of general formula I according to claim 1 , and a pharmaceutically acceptable carrier.
14. A method for treating cancer selected from breast, lung, colon, and prostate cancers comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .
15. A method for inhibiting a cyclin-dependent kinase selected from CDK1 and CDK2 comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .
16. A method for inhibiting VEGF-receptor tyrosine kinases comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .
17. The method according to claim 14 , in which the cancer is breast cancer.
18. The method according to claim 14 , in which the cancer is lung cancer.
19. The method according to claim 14 , in which the cancer is colon cancer.
20. The method according to claim 14 , in which the cancer is prostate cancer.