CDK-inhibitory pyrimidines, their production and use as pharmaceutical agents

A compound of formula I

• wherein
• R1 stands for hydrogen, halogen, C1-C6-alkyl, —COR5, —OCF3, or —(CH2)nR5, —S—CF3 or —SO2CF3,
• R2 stands for C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, or C3-C10-cycloalkyl, or for C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, or C3-C10-cycloalkyl each of which is substituted in one or more places in the same way or differently with hydroxy, halogen, C1-C6-alkoxy, C1-C6-alkylthio, amino, cyano, C1-C6-alkyl, —NH—(CH2)n—C3-C10-cycloalkyl, C3-C10-cycloalkyl, C1-C6-hydroxyalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkoxy-C1-C6-alkyl, —NHC1—C6-alkyl, —N(C1-C6-alkyl)2, —SO(C1-C6-alkyl), —SO2(C1-C6-alkyl), C1-C6-alkanoyl, —CONR3R4, —COR5, C1-C6-alkylOAc, carboxy, aryl, —(CH2)n-aryl, phenyl-(CH2)n—R5, —(CH2)nPO3(R5)2 or with the group —R6 or —NR3R4, and the phenyl, C3-C10-cycloalkyl, aryl and —(CH2)n-aryl groups themselves optionally can be substituted in one or more places in the same way or differently with halogen, hydroxy, C1-C6-alkyl, C1-C6-alkoxy, benzoxy or with the group —CF3 or —OCF3, and the ring of the C3-C10-cycloalkyl 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 C1-C10 alkyl optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms or
• R2 stands for the group
• X stands for oxygen or for the group —NH—, or —N(C1-C3-alkyl)- or for —OC3—C10-cycloalkylene,
• or
• X and R2 together form a C3-C10-cycloalkyl ring, which optionally can be substituted in one or mow places with hydroxy, C1-C6-alkyl, C1-C6-alkoxy or halogen,
• A and B, in each case independently of one another, stand for
• hydroxy, or for the group —SR7,
• —S(O)R7, —SO2R7, —NHSO2, R7, —CH(OH)R7, —CR7(OH)—R7,
• C1-C6-alkylP(O)OR3OR4 or —COR7, or for
• or
• A and B together form a C3-C10-cycloalkyl ring that optionally 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 the C3-C10-cycloalkyl ring optionally can be substituted in one or more places in the same way or differently with hydroxy, halogen, C1-C6-alkoxy, C1-C6-alkylthio, amino, cyano, C1-C6-alkyl, C2-C6-alkenyl, C3-C10-cycloalkyl, C1-C6-alkoxy-C1-C6-alkyl, —NHC1—C6-alkyl, —N(C1-C6-alkyl)2, —SO(C1-C6-alkyl), —SO2R7, C1-C6-alkanoyl, —CONR3R4, —COR5, C1-C6-alkoxyOAc, phenyl or with the group R6, whereby the phenyl itself optionally can be substituted in one or more places in the same way or differently with halogen, hydroxy, C1-C6-alkyl, C1-C6-alkoxy or with the group —CF3 or —OCF3,
• R3 and R4, in each case independently of one another, stand for hydrogen, phenyl, benzyloxy, C1-C12-alkyl, C1-C6-alkoxy, C2-C4-alkenyloxy, C3-C6-cycloalkyl, hydroxy, hydroxy-C1-C6-alkyl, dihydroxy-C1-C6-alkyl, C3-C6-cycloalkyl-C1-C3-alkyl that is optionally substituted with cyano, or for
• C1-C6-alkyl that is optionally substituted in one or more places in the same way or differently with phenyl, phenyloxy, C3-C6-cycloalkyl, C1-C6-alkyl or C1-C6-alkoxy, wherein the phenyl itself can be substituted in one or more places in the same way or differently with halogen, C1-C6-alkyl, C1-C6-alkoxy or with the group —SO2NR3R4, or for the group —(CH2)nNR2R4, —CNHNH2 or —NR3R4,
• or
• R3 and R4 together form a C3-C10-cycloalkyl ring that optionally 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,
• R5 stands for hydroxy, phenyl, C1-C6-alkyl, C3-C6-cycloalkyl, benzoxy, C1-C6-alkylthio or C1-C6-alkoxy,
• R6 stands for a C3-C10-cycloalkyl ring, that optionally 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,
• R7 stands for halogen, hydroxy, phenyl, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C10-cycloalkyl, with the above-indicated meaning, or for the group —NR3R4, or for a C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl or C3-C7-cycloalkyl that is substituted in one or more places in the same way or differently with hydroxy, C1-C6-alkoxy, halogen, phenyl, —NR3R4 or phenyl, which itself can be substituted in one or more places in the same way or differently with halogen, hydroxy, C1-C6-alkyl, C1-C6-alkoxy, halo-C1-C6-alkyl, halo-C1-C6-alkoxy, or R7 stands for phenyl, which itself can be substituted in one or more places in the same way or differently with halogen, hydroxy, C1-C6-alkyl or C1-C6-alkoxy, halo-C1-C6-alkyl, or halo-C1-C6-alkoxy,
• R8, R9 and
• R10, in each case independently of one another, stand for hydrogen, hydroxy, C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, C3-C10-cycloalkyl, aryl, or for C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl or C3-C10-cycloalkyl that is optionally substituted in one or more places in the same way or differently with hydroxy, halogen, C1-C6-alkoxy, C1-C6-alkylthio, amino, cyano, C1-C6-alkyl, —NH—(CH2)n—C3-C10-cycloalkyl, C3-C10-cycloalkyl, C1-C6-hydroxyalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkoxy-C1-C6-alkyl, —NHC1—C6-alkyl, —N(C1-C6-alkyl)2, —SO(C1-C6-alkyl), —SO(C1-C6-alkyl), C1-C6-alkanoyl, —CONR3R4, —COR5, C1-C6-alkylOAc, carboxy, aryl, —(CH2)n-aryl, phenyl-(CH2)n—R5, —(CH2)nPO3(R5)z or with the group —R6 or —NR3R4, and the phenyl, C3-C10-cycloalkyl, aryl, and —(CH2)n-aryl itself optionally can be substituted in one or more places in the same way or differently with halogen, hydroxy, C1-C6-alkyl, C1-C6-alkoxy or with the group —CF3 or —OCF3, and the ring of C3-C10-cycloalkyl 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 C1-C10 alkyl optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and
• n stands for 0-6,
• or
• a pharmaceutically acceptable salt thereof.

A compound of formula I

• wherein
• R1 stands for hydrogen, halogen, C1-C6-alkyl, nitro, —COR5, —OCF3, or —(CH2)nR5, —S—CF3 or —SO2CF3,
• R2 stands for C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, or C3-C10-cycloalkyl, or for C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, or C3-C10-cycloalkyl each of which is substituted in one or more places in the same way or differently with hydroxy, halogen, C1-C6-alkoxy, C1-C6-alkylthio, amino, cyano, C1-C6-alkyl, —NH—(CH2)n—C3-C10-cycloalkyl, C3-C10-cycloalkyl, C1-C6-hydroxyalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkoxy-C1-C6-alkyl, —NHC1—C6-alkyl, —N(C1-C6-alkyl)2, —SO(C1-C6-alkyl), —SO2(C1-C6-alkyl), C1-C6-alkanoyl, —CONR3R4, —COR5, C1-C6-alkylOAc, carboxy, aryl, —(CH2)n-aryl, phenyl-(CH2)n—R5, —(CH2)nPO3(R5)2 or with the group —R6 or —NR3R4, and the phenyl, C3-C10-cycloalkyl, aryl and —(CH2)-aryl groups themselves optionally can be substituted in one or more places in the same way or differently with halogen, hydroxy, C1-C6-alkyl, C1-C6-alkoxy, benzoxy or with the group —CF3 or —OCF3, and the ring of the C3-C10-cycloalkyl 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 C1-C10 alkyl optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms or
• R2 stands for the group
• X stands for oxygen or for the group —NH—, or —N(C1-C3-alkyl)- or for —OC3—C10-cycloalkylene,
• or
• X and R2 together form a C3-C10-cycloalkyl ring, which optionally can be substituted in one or more places with hydroxy, C1-C6-alkyl, C1-C6-alkoxy or halogen,
• A and B, in each case independently of one another, stand for
• hydroxy, or for the group —SR7
• —S(O)R7, —SO2R7, —NHSO2R7, —CH(OH)R7, —CR7(OH)—R7,
• C1-C6-alkylP(O)OR3OR4 or —COR7, or for
• or
• A and B together form a C3-C10-cycloalkyl ring that optionally 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 the C3-C10-cycloalkyl ring optionally can be substituted in one or more places in the same way or differently with hydroxy, halogen, C1-C6-alkoxy, C1-C6-alkylthio, amino, cyano, C1-C6-alkyl, C2-C6-alkenyl, C3-C10-cycloalkyl, C1-C6-alkoxy-C1-C6-alkyl, —NHC1—C6-alkyl, —N(C1-C6-alkyl)2, —SO(C1-C6-alkyl), —SO2R7, C1-C6-alkanoyl, —CONR3R4, —COR5, C1-C6-alkoxyOAc, phenyl or with the group R6, whereby the phenyl itself optionally can be substituted in one or more places in the same way or differently with halogen, hydroxy, C1-C6-alkyl, C1-C6-alkoxy or with the group —CF3 or —OCF3,
• R3 and R4, in each case independently of one another, stand for hydrogen, phenyl, benzyloxy, C1-C12-alkyl, C1-C6-alkoxy, C2-C4-alkenyloxy, C3-C6-cycloalkyl, hydroxy, hydroxy-C1-C6-alkyl, dihydroxy-C1-C6-alkyl, C3-C6-cycloalkyl-C1-C3-alkyl that is optionally substituted with cyano, or for
• C1-C6-alkyl that is optionally substituted in one or more places in the same way or differently with phenyl, phenyloxy, C3-C6-cycloalkyl, C1-C6-alkyl or C1-C6-alkoxy, wherein the phenyl itself can be substituted in one or more places in the same way or differently with halogen, C1-C6-alkyl, C1-C6-alkoxy or with the group —SO2NR3R4, or for the group —(CH2)nNR3R4, —CNHNH2 or —NR3R4,
• or
• R3 and R4 together form a C3-C10-cycloalkyl ring that optionally 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,
• R5 stands for hydroxy, phenyl, C1-C6-alkyl, C3-C6-cycloalkyl, benzoxy, C1-C6-alkylthio or C1-C6-alkoxy,
• R6 stands for a C3-C10-cycloalkyl ring, that optionally 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,
• R7 stands for halogen, hydroxy, phenyl, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C10-cycloalkyl, with the above-indicated meaning, or for the group —NR3R4, or for a C1-C10-alkyl, C3-C10-alkenyl, C2-C10-alkynyl or C3-C7-cycloalkyl that is substituted in one or more places in the same way or differently with hydroxy, C1-C6-alkoxy, halogen, phenyl, —NR3R4 or phenyl, which itself can be substituted in one or more places in the same way or differently with halogen, hydroxy, C1-C6-alkyl, C1-C6-alkoxy, halo-C1-C6-alkyl, halo-C1-C6-alkoxy, or R7 stands for phenyl, which itself can be substituted in one or more places in the same way or differently with halogen, hydroxy, C1—C6-alkyl or C1-C6-alkoxy, halo-C1-C6-alkyl, or C1-C6-alkoxy,
• R8, R9 and
• R10, in each case independently of one another, stand for hydrogen, hydroxy, C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, C3-C10-cycloalkyl, aryl, or for C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl or C3-C10-cycloalkyl that is optionally substituted in one or more places in the same way or differently with hydroxy, halogen, C1-C6-alkoxy, C1-C6-alkylthio, amino, cyano, C2-C6-alkyl, —NH—(CH2)n—C3-C10-cycloalkyl, C3-C10-cycloalkyl, C1-C6-hydroxyalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-alkoxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkoxy-C1-C6-alkyl, —NHC1—C6-alkyl, —N(C1-C6-alkyl)2, —SO(C1-C6-alkyl), —SO1(C1—C6-alkyl), C1-C6-alkanoyl, —CONR3R4, —COR5, C1-C6-alkylOAc, carboxy, aryl, —(CH2)n-aryl, phenyl-(CH2)n—R5, —(CH2)nPO3(R5)2 or with the group —R6 or —NR3R4, and the phenyl, C3-C10-cycloalkyl, aryl, and —(CH2)n-aryl itself optionally can be substituted in one or more places in the same way or differently with halogen, hydroxy, C1-C6-alkyl, C1-C6-alkoxy or with the group —CF3 or —OCF3, and the ring of C3-C10-cycloalkyl 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 C1-C10 alkyl optionally can be interrupted by one or more nitrogen, oxygen and/or sulfur atoms and
• n stands for 0-6,
• or
• a pharmaceutically acceptable salt thereof.