Substituted quinolin-2-one derivatives useful as antiproliferative agents

A compound of the formula 1 or 2:

• 15
• or a pharmaceutically acceptable salt, solvate or prodrug thereof wherein:
• the dashed lines in formulas 1 and 2 indicate an optional second bond connecting C-3 and C-4 of the quinolin-2-one rings;
• Z is an aromatic 4 to 10 membered heterocyclic group, substituted with 1 to 4 R3 substituents;
• R1 is selected from H, C1-C10 alkyl, —(CR11R12)qC(O)R10, —(CR11R12)qC(O)OR9, —(CR11R12)qOR10, —(CR11R12)qC(R11)(R12)SO2R9, —(CR11R12)t(C3-C10 cycloalkyl), —(CR11R12)t(C6-C10 aryl), and —(CR11R12)t(4 to 10 membered heterocyclic), wherein each t is independently an integer from 0 to 5 and each q is independently an integer from 1 to 5;
• said cycloalkyl, aryl and heterocyclic R1 groups are optionally fused to a C6-C10 aryl group, a C5-C8 saturated cyclic group, or a 4 to 10 membered heterocyclic group;
• and the foregoing R1 groups, except H but including any optional fused rings referred to above, are optionally substituted with 1 to 4 R3 groups;
• R2 is halo, cyano, —C(O)OR10, or a group selected from the substituents provided in the definition of R10;
• each R3, R4 and R5 is independently selected from H, R10, C2-C10 alkenyl, C2-C10 alkynyl, halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, —OR10, —C(O)R10, —C(O)OR10, —NR11C(O)OR10, —OC(O)R10, —NR11SO2R10, —SO2NR10R11, —NR11C(O)R10, —C(O)NR10R11, —NR10R11, —CH═NOR10, —S(O)jR10, —(CR11R12)tC≡CR10, and —(CR11R12)tC≡CR13, wherein each t is independently an integer from 0 to 5 and each j is independently an integer from 0 to 2;
• said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heterocyclic moieties of the foregoing R3, R4, and R5 groups are optionally substituted by 1 to 3 substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, —NR11SO2(C1-C6 alkyl), —SO2NR11R12, —C(O)R10, —C(O)OR10, —OC(O)R10, —NR11C(O)OR10, —NR11C(O)R10, —C(O)NR11R12, —NR11R12, hydroxy, C1-C6 alkoxy, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, —(CR11R12)t(C6-C10 aryl), —(CR11R12)t(C3-C10 cycloalkyl), and —(CR11R12)t(4 to 10 membered heterocyclic), wherein each t is independently an integer from 0 to 5;
• R6 is H, cyano, —(CR11R12)t(4 to 10 membered heterocyclic) wherein t is an integer from 0 to 5, —OR10, —OC(O)R10, —NR11R11, —NR11C(O)H, —C(O)OR10, or —SR10, wherein heterocyclic groups of said R6 groups are optionally substituted by 1 to 4 R3 groups;
• R7 is —(CR11R12)t(imidazolyl) or —(CR11R12)t(pyridinyl), wherein each t is an integer from 0 to 5 and said imidazolyl and pyridinyl moieties are optionally substituted by up to 2 R3 substituents;
• R8 is phenyl or an aromatic 4 to 10 membered heterocyclic group, and said R8 group is optionally substituted by 1 to 4 R3 substituents;
• each R10 is independently selected from H, C1-C10 alkyl, —(CR11R12)t(C3-C10 cycloalkyl), —(CR11R12)t(C6-C10 aryl), and —(CR11R12)t(4 to 10 membered heterocyclic);
• wherein each t is independently an integer from 0 to 5 and said cycloalkyl, aryl and heterocyclic R10 groups are optionally fused to a C6-C10 aryl group, a C5-C8 saturated cyclic group, or a 4 to 10 membered heterocyclic group;
• and the foregoing R10 substituents, except H but including any optional fused rings, are optionally substituted by 1 to 3 substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, —C(O)R11, —C(O)OR11, —OC(O)R11, —NR11C(O)R12, —C(O)NR11R12, —NR11R12, hydroxy, C1-C6 alkyl, and C1-C6 alkoxy;
• each R11 and R12 is independently H or C1-C6 alkyl, and where R11 and R12 are as —(CR11R12)q or —(CR11R12)t each is independently defined for each iteration of q or t in excess of 1;
• R13 is selected from the list of substituents provided in the definition of R10 and —SiR14R15R16;
• and,
• R14, R15 and R16 are each independently selected from the substituents provided in the definition of R10 except at least one of R14, R15 and R16 is not H.