Pyrimido compounds having antiproliferative activity

A compound of formula:

• 43
• or a pharmaceutically acceptable salt thereof, wherein
• R1 is selected from the group
• H,
• C1-10 alkyl,
• C1-10 alkyl substituted by up to three groups selected from aryl, cycloalkyl, heteroaryl, heterocycle, NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2, wherein the aryl, cycloalkyl, heteroaryl, and heterocycle groups may each independently be substituted by up to three groups selected from NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2,
• aryl,
• aryl substituted by up to three groups selected from lower alkyl, NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2,
• heteroaryl,
• heteroaryl substituted by up to three groups selected from lower alkyl, NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2,
• heterocycle,
• heterocycle substituted by up to three groups selected from lower alkyl, NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2,
• C3-10 cycloalkyl,
• C3-10 cycloalkyl substituted by up to three groups selected from lower alkyl NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2,
• C2-10 alkenyl,
• C2-10 alkenyl substituted by up to three groups selected from NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2, and
• C2-10 alkynyl, substituted by up to three groups selected from NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2;
• R2, R3 and R4 are independently selected from the group consisting of
• H,
• NR10R11,
• OR12,
• SR12,
• C1-10 alkyl,
• C1-10 alkyl substituted by up to three groups selected from cycloalkyl, heteroaryl, heterocycle, NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2;
• and wherein the cycloalkyl, heteroaryl, and heterocycle groups may each independently be substituted by up to three groups selected from lower alkyl, NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2,
• heteroaryl, heteroaryl substituted by up to three groups selected from lower alkyl, NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2,
• heterocycle, substituted by up to three groups selected from lower alkyl, NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2,
• C3-10 cycloalkyl,
• C3-10 cycloalkyl substituted by up to three groups selected from lower alkyl, NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2,
• C2-10 alkenyl,
• C2-10 alkenyl substituted by up to three groups selected from NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2,
• C2-10 alkynyl, and
• C2-10 alkynyl substituted by up to three groups selected from NR10R11, OR12, SR12, halogen, COR13, CO2R13, CONR13R14, SO2NR13R14, SOR13, SO2R13, CN and NO2,
• Provided that at least one of R2, R3 or R4 is not H.
• R5, R6, R7 and R8 are independently selected from the group
• H,
• lower alkyl,
• lower alkyl substituted by hydroxy or alkoxy,
• NR15R16,
• OH,
• OR17,
• SR17,
• halogen,
• COR17,
• CO2R17,
• CONR17R18,
• SO2NR17R18,
• SOR17,
• SO2R17, and
• CN;
• R9 is selected from the group
• H,
• 44
• and
• COR17;
• R10 and R11 are independently selected from the group
• H,
• COR13,
• CO2R13,
• CONR13R14,
• SO2R13,
• SO2NR13R14,
• lower alkyl,
• lower alkyl substituted by hydroxy, alkoxy or NR15R16,
• cycloalkyl,
• cycloalkyl substituted by hydroxy, alkoxy, lower alkyl, or NR15R16,
• heterocycle, and
• heterocycle substituted by hydroxy, alkoxy, lower alkyl, or NR15R16,
• or, alternatively, NR10R11 can form a ring having 3 to 7 atoms, said ring optionally including one or more additional hetero atoms and being optionally substituted by the group consisting of one or more lower alkyl, OR12, COR13, CO2R13, CONR13R14, SOR13, SO2R13, and SO2NR13R14,
• R12 is selected from the group
• H,
• lower alkyl,
• COR13,
• CONR13R14,
• C2-6 alkyl substituted by hydroxy, alkoxy, or NR15R16, cycloalkyl,
• cycloakyl substituted by hydroxy, alkoxy, lower alkyl, or NR15R16,
• heterocycle, and
• heterocycle substituted by hydroxy, alkoxy, lower alkyl, or NR15R16;
• R13 and R14 are independently selected from the group
• H,
• lower alkyl,
• C2-6 alkyl substituted by hydroxy, alkoxy, or NR15R16,
• cycloalkyl,
• cycloaklyl substituted by hydroxy, alkoxy, lower alkyl, or NR15R16,
• heterocycle, and
• heterocycle substituted by hydroxy, alkoxy, lower alkyl, or NR15R16,
• or, alternatively, NR13R14 can form a ring having 3 to 7 atoms, said ring optionally including one or more additional hetero atoms and being optionally substituted by the group consisting of one or more lower alkyl, OR17, COR17, CO2R17, CONR17R18, SO2R17, and SO2NR17R18;
• R15 is selected from the group
• H,
• lower alkyl,
• COR17, and
• CO2R17;
• and
• R16, R17 and R18 are independently selected from the group
• H, and
• lower alkyl,
• or, alternatively, NR15R16 and NR17R18 can each independently form a ring having 3 to 7 atoms, said ring optionally including one or more additional hetero atoms;
• R19 and R20 are independently selected from the group
• H, and
• lower alkyl;
• and
• R21 is selected from
• lower alkyl, and
• C2-6 alkyl substituted by hydroxy, alkoxy or NR15R16,
• or a pharmaceutically acceptable salt thereof.