Diaminothiazoles having antiproliferative activity

A compound of formula:

• or the pharmaceutically acceptable salts or esters thereof, wherein
• R1 is selected from the group consisting of
• H,
• lower alkyl that optionally may be substituted with a group selected from OR6, cycloalkyl, and NR7R8,
• cycloalkyl,
• COR9, and
• SO2R10;
• R2 is selected from the group consisting of
• H,
• F,
• Cl, and
• CH3;
• R5 is selected from the group consisting of
• H,
• lower alkyl, which optionally may be substituted with a group selected from OR6 and NR7R8,
• OR11,
• NR12R13,
• halogen,
• NO2,
• CONR6R9,
• NHSO2R14,
• CN
• S-lower alkyl,
• OCF3, and
• OCHF2,
• R3 and R4 taken together with the two carbons and the bond between them from the benzene ring (D) to which R3 and R4 are attached form a ring system having up to two additional rings, each of said rings having 5–7 atoms, and the ring attached to the benzene ring (D) optionally including one or more hetero atoms and being optionally substituted by lower alkyl,
• R6 and R9 are independently selected from the group consisting of
• H, and
• lower alkyl that optionally may be substituted by OH and halogen;
• R7 and R8 are independently selected from the group consisting of
• H, and
• lower alkyl that optionally may be substituted by OR6,
• or, alternatively, R7 is H and R8 is OH,
• or, alternatively, NR7R8 can optionally form a ring having 5–6 atoms, said ring optionally including one or more additional hetero atoms and being optionally substituted by the group consisting of one or more of OR6 and lower alkyl which itself may be optionally substituted by OH;
• R10 is selected from the group consisting of
• lower alkyl which optionally may be substituted by one or more chlorine or fluorine, and
• NH2;
• R11 is selected from the group consisting of
• H, and
• lower alkyl that optionally may be substituted by OR6, COOH, halogen and NR15R16;
• R12 and R13 are independently selected from the group consisting of
• H,
• lower alkyl that optionally may be substituted with a group selected from OR6, COOH and NR15R16,
• COR17, and
• SO2R18,
• provided that only one of R12 and R13 is COR17 or SO2R18,
• or alternatively NR12R13 can optionally form a ring having 5–6 atoms, said ring optionally including one or more additional hetero atoms and being optionally substituted by the group consisting of one or more of OR6 and lower alkyl which itself may be optionally substituted by OH;
• R14 is tower alkyl;
• R15 and R16 are independently selected from the group consisting of
• H, and
• lower alkyl that optionally may be substituted by OH,
• or alternatively NR15R16 can optionally form a ring having 5–6 atoms, said ring optionally including one or more additional hetero atoms and being optionally substituted by the group consisting of one or more of OR6 and lower alkyl which itself may be optionally substituted by OH;
• R17 is selected from the group consisting of
• H, and
• lower alkyl which optionally may be substituted with a group selected from OH, COOH and NR15R16;
• and
• R18 is lower alkyl.