2-indolinone derivatives as modulators of protein kinase activity

An 2-indolinone having the chemical structure:

• 15
• or a physiologically acceptable salt or prodrug thereof, wherein:
• A, B, D and E are independently selected from the group consisting of carbon and nitrogen wherein it is understood that, when A, B, D or E is nitrogen, R6, R7, R8 or R9, respectively, does not exist;
• G and J are selected from the group consisting of nitrogen and carbon such that, when G is nitrogen, J is carbon and when J is nitrogen, G is carbon, it being recognized that, when G or J is nitrogen, R5 or. R5′, respectively, does not exist;
• R1 and R3 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, C-carboxy, O-carboxy, C-amido, C-thioamido, sulfonyl and trihalomethylsulfonyl;
• R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl and halo;
• R4, R5 and R5′are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicylic, halo, hydroxy, nitro, cyano, alkoxy, aryloxy, C-carboxy, O-carboxy, carbonyl, S-sulfonamido, amino and NR10R11 wherein
• R10 and R11 are independently selected from the group consisting of alkyl, cycloalkyl, aryl, carbonyl, sulfonyl, tri-halomethanesulfonyl and, combined, a five-member or a six-member heteroalicyclic ring;
• R6, R7, R8 and R9 are independently selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, S-sulfonamido, N-sulfonamido, N-trihalomethanesulfonamido, carbonyl, C-carboxy, O-carboxy, cyano, nitro, halo, cyanato, isocyanato, thiocyanato, isothiocyanato, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, amino and —NR10R11 with R10 and R11 as defined above;
• and,
• R6 and R7 or R7 and R8 or R1 and R9, combined, may form a five- or six-member aromatic, heteroaromatic, alicyclic or heteroalicyclic ring group.