Indazole inhibitors of the wnt signal pathway and therapeutic uses thereof

A compound or pharmaceutically acceptable salt or prodrug thereof having the structure of formula Ia:

• wherein:
• R1, R2, R4, R6, R7 and R8 are independently selected from the group consisting of H, C1-9 alkyl, halide, —CF3, —(C1-9 alkyl)ncarbocyclylR13, —(C1-9 alkyl)nheterocyclylR13, —(C1-9 alkyl)narylR13, —(C1-9 alkyl)nheteroarylR13, —(C1-9 alkyl)nOR10, —(C1-9 alkyl)nSR10, —(C1-9 alkyl)nS(═O)R11, —(C1-9 alkyl)nSO2R10, —(C1-9 alkyl)nN(R10)SO2R10, —(C1-9 alkyl)nSO2N(R10)2, —(C1-9 alkyl)nN(R10)2, —(C1-9 alkyl)nN(R10)C(=A)N(R10)2, —(C1-9 alkyl)nC(=A)N(R10)2, —(C1-9 alkyl)nN(R10)C(=A)R10, —NO2, —CN, —(C1-9 alkyl)nCO2R10 and —(C1-9 alkyl)nC(=A)R10;
• R3 is selected from the group consisting of —NRS(═O)R14, —(C1-9alkyl)R14, -carbocyclylR14R15, -heterocyclylR14R15, -arylR14R15 and -heteroarylR14R15;
• alternatively, one of each R1 and R2, R2 and R3, R3 and R4, R6 and R7, or R7 and R8 are taken together to form a ring which is selected from the group consisting of aryl, heteroaryl,
• wherein each bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond;
• each R10 is independently selected from the group consisting of H, —C1-9 alkyl, —CF3, —(C1-9 alkyl)ncarbocyclyl, —(C1-9 alkyl)nheterocyclyl, —(C1-9 alkyl)naryl and —(C1-9 alkyl)nheteroaryl;
• each R11 is independently selected from the group consisting of —C1-9 alkyl, —CF3, —(C1-9 alkyl)ncarbocyclyl, —(C1-9 alkyl)nheterocyclyl, —(C1-9 alkyl)naryl and —(C1-9 alkyl)nheteroaryl;
• each R12 is independently selected from the group consisting of —OR10 and R10;
• each R13 is 1-5 substituents each selected from the group consisting of H, C1-9 alkyl, halide, —CF3, carbocyclyl, heterocyclyl, aryl, heteroaryl, —(C1-9 alkyl)nOR10, —(C1-9 alkyl)nSR10, —(C1-9 alkyl)nS(═O)R11, —(C1-9 alkyl)nSO2R10, —(C1-9 alkyl)nN(R10)SO2R10, —(C1-9 alkyl)nSO2N(R10)2, —(C1-9 alkyl)nN(R10)2, —(C1-9 alkyl)nN(R10)C(=A)N(R10)2, —(C1-9 alkyl)nC(=A)N(R10)2, —(C1-9 alkyl)nN(R10)C(=A)R10, —NO2, —CN, —(C1-9 alkyl)nCO2R10 and —(C1-9 alkyl)nC(=A)R10;
• R14 is selected from the group consisting of —NR10)C(=A)R10, —NR10S(═O)R11, —NR10SO2R10, —NR10)C(═O)N(R16)2, —NR10)C(═S)N(R10)2, —NR10)C(═NR12)N(R10)2, —N(R16)2, —C(═O)NR10R17, —C(═S)N(R10)2, —C(═NR12)N(R10)2, —OC(=A)R10, —C(=A)R10, —NR10)C(=A)OR10 and —OC(=A)NR10R10;
• R15 is 1-4 substituents each selected from the group consisting of H, C1-9 alkyl, halide, —CF3, carbocyclylR13, heterocyclylR13, arylR13, heteroarylR13, —(C1-9 alkyl)nOR10, —(C1-9 alkyl)nSR10, —(C1-9 alkyl)nS(═O)R11, —(C1-9 alkyl)nSO2R10, —(C1-9 alkyl)nN(R10)SO2R10, —(C1-9 alkyl)nSO2N(R10)2, —(C1-9 alkyl)nN(R10)2, —(C1-9 alkyl)nN(R10)C(=A)N(R10)2, —(C1-9 alkyl)nC(=A)N(R10)2, —(C1-9 alkyl)nN(R10)C(=A)R10, —NO2, —CN, —(C1-9 alkyl)nCO2R10 and —(C1-9 alkyl)nC(=A)R10;
• R16 is —C1-9 alkyl;
• each R17 is independently selected from the group consisting of -heterocyclylR13, —(C1-9 alkyl)heterocyclylR13 and —(C1-9 alkyl)carbocyclylR13;
• R18 and R19 are independently selected from the group consisting of H, C1-9 alkyl, halide, —(C1-9 alkyl)ncarbocyclylR13, —(C1-9 alkyl)nheterocyclylR13, —(C1-9 alkyl)narylR13, —(C1-9 alkyl)nheteroarylR13, —(C1-9 alkyl)nOR10, —(C1-9 alkyl)nSR10, —(C1-9 alkyl)nS(═O)R11, —(C1-9 alkyl)nSO2R10, —(C1-9 alkyl)nN(R10)SO2R10, —(C1-9 alkyl)nSO2N(R10)2, —(C1-9 alkyl)nN(R10)2, —(C1-9 alkyl)nN(R10)C(=A)N(R10)2, —(C1-9 alkyl)nC(=A)N(R10)2, —(C1-9 alkyl)nN(R10)C(=A)R10, —NO2, —CN, —(C1-9 alkyl)nCO2R10 and —(C1-9 alkyl)nC(=A)R10;
• alternatively, R18 and R19 are taken together to form a ring which is selected from the group consisting of benzene and pyridine;
• each A is independently selected from O, S and NR12;
• Y1, Y2, and Y3 are C;
• Y4 is nitrogen and R9 is absent;
• and
• each n is 0 or 1.