4-heteroaryl-3-heteroarylidenyl-2-indolinones and their use as protein kinase inhibitors

A compound of the formula:

• wherein:
• R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, —CX3, hydroxy, alkoxy, nitro, cyano, —C(O)R26, —C(O)OR26, R26C(O)O—, —C(O)NR28R29, R26C(O)NR28—, —NR28R29, —S(O)2R26, —S(O)2OR26, —S(O)2NR28R29, R26S(O)2NR28—, X3CS(O)2— and X3CS(O)2NR28— where X is F, Cl, Br, or I;
• wherein:
• D is carbon or nitrogen;
• R8, R9, R11 and R12 are independently selected from the group consisting of hydrogen, alkyl, hydroxy, alkoxy, halo, nitro, cyano and —NR28R29;
• Z is selected from the group consisting of oxygen, sulfur, and —NR10;
• R10 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, —C(O)R26, —C(S)R26, —C(O)R26, —C(O)NR28R29, —C(S)NR28R29, —C(NH)NR28R29 and —S(O)2R26;
• Q is selected from the group consisting of:
• where:
• G1, G2, G3, G4 and G5 are selected from the group consisting of carbon and nitrogen with the proviso that no more than two of G1, G2, G3, G4 and G5 are nitrogen;
• R17, R8, R19, R20 and R21 are independently selected from the group consisting of hydrogen, alkyl, hydroxy, alkoxy, halo, —NR28R29,—(CH2)nC(O)R26, —(CH2)nC(O)OR26 and —(CH2)nC(O)NR28R29, —(CH2)nNR28R29, —(CH2)nS(O)2R26 and —CH2)nS(O)2NR28R29;
• J1 is selected from the group consisting of nitrogen, oxygen and sulfur such that when J1 is nitrogen, R22 is selected from the group consisting of hydrogen, alkyl and —C(O)R26;
• and when J1 is oxygen or sulfur, R22 does not exist;
• J2, J3 and J4 are selected from the group consisting of carbon and nitrogen;
• R23, R24 and R25 are independently selected from the group consisting of hydrogen, alkyl, aryl optionally substituted with one or more groups independently selected from the group consisting of hydroxy, unsubstituted lower alkoxy and halo, halo,
• —(CH2)nC(O)R26, —(CH2)nC(O)OR26 and —CH2)nC(O)NR28R29, —(CH2)nNR28R29,
• —(CH2)nS(O)2R26, —(CH2)nS(O)2NR28R29, —(CH2)nOR26, —O(CH2)nNR28R29 and
• —C(O)NH(CH2)nNR28R29;
• n is 0, 1, 2, or 3;
• R23 and R24 or R24 and R25 may combine to form a group selected from the group consisting of —CH2CH2CH2CH2—, —CH═CR33CR34═CH— and
• —C(O)Y(CH2)2— and group wherein Y is selected from the group consisting of oxygen, sulfur and N(R27)— and R33 and R34 are selected from the group consisting of hydrogen, —(CH2)nNR28R29 and —O(CH2)nNR28R29 where, when one of R33 or R34 is —(CH2)nNR28R29 or —O(CH2)nNR28R29, the other is hydrogen;
• it being understood that, when J2, J3 or J4 is nitrogen, R23, R24 or R25, respectively, does not exist;
• R26 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl and heteroaryl;
• R27 is selected from the group consisting of hydrogen and alkyl;
• R28 and R29 are independently selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, —(CH2)naryl, —(CH2)nheteroaryl and —C(O)R26, or, combined, R28 and R29 may form a group selected from the group consisting of —(CH2)5—, —(CH2)2O(CH2)2—, —CH2)2NR30(CH2)2— and —(CH)3C(O)— wherein R30 is selected from the group consisting of hydrogen, alkyl, —C(O)R26, —S(O)2R26, —S(O)3R26, —S(O)2NR31R32, —C(O)NHNR31R32, —C(O)NR31R32, —C(S)NR31R32 and —C(O)0R26 where R31 and R32 are independently selected from the group consisting of hydrogen, unsubstituted lower alkyl and aryl optionally substituted with one or more groups independently selected from the group consisting of halo and unsubstituted lower alkoxy;
• or
• a pharmaceutically acceptable salt thereof.