4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors

A compound of Formula 1

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is H or methyl;
• each of R2 and R3 is independently H, halogen, (C1-3)alkyl, or (C1-3)alkoxy;
• or R2 and R3 taken together form an optionally substituted methylindene selected from the group consisting of:
• wherein:
• n is an integer of 0-3;
• each R7 is independently H, alkyl, carboxylic acid, amine, halogen, nitro, cyano, X1, X2—(C1-C4)alkyl-R8, X2-(C2-C4)alkenyl-R8, or X2—(C2-C4)alkynyl-R8;
• X1 is —C(O)NR9—, —NR9C(O)—, —C(O)O—, C(O)R11, —OC(O)—, —O—, —NR9—, —S—, —S(O2), or —S(O2)NR9—;
• X2 is a chemical bond, —C(O)NR9—, —NR9C(O)—, —C(O)O—, C(O)R11, —OC(O)—, —O—, —NR9—, —S—, —S(O2), or —S(O2)NR9—;
• R8 is selected from the group consisting of hydrogen, dialkylamino, carboxyl, hydoxyl, alkoxy, sulfonamide, urea, carbamate, diol, alkylsulphonyl, and R10;
• R9 is H or (C1-C3)alkyl;
• R10 is an optionally substituted 5- or 6-membered saturated, unsaturated, or aromatic heterocycle comprising having from 1 to 4 heteroatoms;
• and
• R11 is an optionally substituted 5- to 6-membered saturated heterocyclic ring;
• or a 3- to 7-membered ring optionally having up to 3 heteroatoms;
• R4 is H, methyl, trifluoromethyl, (C1-4)alkyl, alkoxy, amido, amino, or optionally substituted aryl;
• X is a chemical bond, ethynyl, —O—, —S—, —S(O)—, —S(O)2—, —NR5C(O)—, or —NR5, wherein R5 is H, methyl, or substituted methylene;
• Y is a 5- to 10-membered mono or bicyclic, saturated, unsaturated, or aromatic ring having up to 3 heteroatoms and optionally substituted;
• and
• Z is N.