Bicyclic pyrimidine and pyrimidine derivatives useful as anticancer agents

A compound of the formula 25 or 26

• 12
• and to pharmaceutically acceptable salts thereof, wherein:
• Z1 is halo, —CO2H, —CONH2, CSNH2 and Z2 is —OR1;
• or
• Z1 is R11 and Z2 is halo;
• or
• Z1 and Z2 are each independently halo;
• X is N or CH;
• wherein R1 is H, C1-C6 alkyl, —C(O)(C1-C6 alkyl), C6-C10 aryl or 5 to 13 membered heterocyclic, wherein said C6-C10 aryl and 5 to 13 membered heterocyclic groups are optionally substituted by 1 to 5 R5 substituents;
• each R5 is independently selected from halo, cyano, nitro, trifluoromethoxy, trifluoromethyl, azido, —C(O)R8, —C(O)OR8, —OC(O)R8, —OC(O)OR8, —NR6C(O)R7, —C(O)NR6R7, —NR6R7, —OR9, —SO2NR6R7, C1-C6 alkyl, —(CH2)jO(CH2)qNR6R7 , —(CH2)tO(CH2)qOR9, —(CH2)tOR9, —S(O)j(C1-C6 alkyl), —(CH2)t(C6-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —C(O)(CH2)t(C6-C10 aryl), —(CH2)tO(CH2)j(C6-C10 aryl), —(CH2)tO(CH2)q(5 to 10 membered heterocyclic), —C(O)(CH2)t(5 to 10 membered heterocyclic), —(CH)jNR7(CH2)qNR6R7, —(CH2)jNR7CH2C(O)NR6R7, —(CH2)jNR7(CH2)qNR9C(O)R8, —(CH2)jNR7(CH2)tO(CH2)qOR9, —(CH2)jNR7(CH2)qS(O)j(C1-C6 alkyl), —(CH2)jNR7(CH2)tR6, —SO2(CH2)t(C6-C10 aryl), and —SO2(CH2)t(5 to 10 membered heterocyclic), wherein j is an integer from 0 to 2, t is an integer from 0 to 6, q is an integer from 2 to 6, the —(CH2)q— and —(CH2)t— moieties of the foregoing R5 groups optionally include a carbon-carbon double or triple bond where t is an integer between 2 and 6, and the alkyl, aryl and heterocyclic moieties of the foregoing R5 groups are optionally substituted by 1 to 3 substituents independently selected from halo, cyano, nitro, trifluoromethyl, azido, —C(O)R8, —C(O)OR8, —OC(O)R8, —OC(O)OR8, —NR6C(O)R7, —C(O)NR6R7, —(CH2)tNR6R7, C1-C6 alkyl, —(CH2)t(C6-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —(CH2)tO(CH2)qOR9, and —(CH2)tOR9, wherein t is an integer from 0 to 6 and q is an integer from 2 to 6;
• each R6 and R7 is independently selected from H, C1-C6 alkyl, —(CH2)t(C6-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —(CH2)tO(CH2)qOR9, and —(CH2)tOR9, wherein t is an integer from 0 to 6 and q is an integer from 2 to 6, and the alkyl, aryl and heterocyclic moieties of the foregoing R6 and R7 groups are optionally substituted by 1 to 3 substituents independently selected from halo, cyano, nitro, trifluoromethyl, azido, —C(O)R8, —C(O)OR8, —CO(O)R8, —OC(O)OR8, —NR9C(O)R10, —C(O)NR9R10, —NR9R10, C1-C6 alkyl, —(CH2)t(C6-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —(CH2)tO(CH2)qOR9, and —(CH2)tOR9, wherein t is an integer from 0 to 6 and q is an integer from 2 to 6, with the proviso that where R6 and R7 are both attached to the same nitrogen, then R6 and R7 are not both bonded to the nitrogen directly through an oxygen;
• each R8 is independently selected from H, C1-C10 alkyl, —(CH2)t(C6-C10 aryl), and —(CH2)t(5 to 10 membered heterocyclic), wherein t is an integer from 0 to 6;
• each R9 and R10 is independently selected from H and C1-C6 alkyl;
• and
• R11 is H, C1-C6 alkyl, —C(O)NR12R13, —C(O)(C6-C10 aryl), —(CH2)t(C6-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —(CH2)tNR12R13, —SO2NR12R13 and —CO2R12, wherein t is an integer from 0 to 6, wherein said R11 groups C1-C6 alkyl, —C(O)(C6-C10 aryl), —(CH2)t(C6-C10 aryl), and —(CH2)t(5 to 10 membered heterocyclic) are optionally substituted by 1 to 5 R5 groups, and wherein each R12 and R13 is independently selected from H, C1-C6 alkyl, —(CH2)t(C3-C10 cycloalkyl), —(CH2)t(C6-C10 aryl), —(CH2)t(5 to 10 membered heterocyclic), —(CH2)tO(CH2)qOR9, —(CH2)tOR9, q is an integer from 2 to 6, and the alkyl, aryl and heterocyclic moieties of the foregoing R12 and R13 groups are optionally substituted by 1 to 3 substituents independently selected from R5 or R12 and R13 taken together with the nitrogen to which they are attached to form a C5-C9 azabicyclic, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl ring, wherein said C5-C9 azabicyclic, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl ring are optionally substituted by 1 to 5 R5 substituents, with the proviso R12 and R13 are not both bonded to the nitrogen directly through an oxygen.