Indolin-2-one derivatives as protein kinase inhibitors

    公开(公告)号:US08946282B2

    公开(公告)日:2015-02-03

    申请号:US13855916

    申请日:2013-04-03

    摘要: A novel class of indoline-2-one derivatives are disclosed. These compounds are protein kinase inhibitors which are useful for treating hyperproliferative diseases such as cancer. In one aspect, the invention relates to a compound a compound of Formula A: or a pharmaceutically acceptable salt thereof, wherein: Ra is hydrogen, (C6-C18)aryl, halo(C6-C18)aryl, or (C1-C6)alkoxy(C6-C18)aryl; Rb is hydrogen, (C3-C18)heteroaryl, (C1-C6)alkoxy(C3-C18)heteroaryl; (C1-C6)alkyl(C3-C18)heteroaryl, (C1-C6)alkyl(C1-C6)alkoxy(C3-C18)heteroaryl, (C1-C6)alkyl(C1-C6)carboxyalkyl(C3-C18)heteroaryl; (C1-C6)alkyl(C1-C6)alkylamino(C1-C6)alkylcarbamoyl)(C3-C18)heteroaryl, (C1-C6)alkyl(C1-C18)aryl(C3-C18)heteroaryl, (C1-C6)alkyl(C1-C6)alkoxycarbonyl)(C3-C18)heteroaryl, (C1-C6)alkyl(C1-C6)alkoxy(C1-C6)oxyalkyl(C3-C18)heteroaryl, (C1-C6)alkyl(C3-C6)heterocyclylcarbonyl(C3-C18)heteroaryl, (C1-C6)alkyl(C3-C6)heterocyclyl(C1-C6)oxyalkyl(C3-C18)heteroaryl, or (C1-C6)alkyl((C3-C6)heterocyclyl(C1-C6)alkylcarbamoyl)(C3-C18)heteroaryl; Rc is hydrogen, (C1-C6)alkoxybenzoylureido, or halo(C6-C18)aryl(C3-C18)heteroarylamido; Rd is hydrogen, halogen, (C1-C6)alkoxybenzoylureido, or halo(C6-C18)aryl(C3-C18)heteroarylamido; Re is-hydrogen, benzoylureido, halobenzoylureido, halo(C1-C6)alkoxybenzoylureido, (C1-C6)alkoxybenzoylureido, (C1-C6)alkylaminobenzoylureido, (C1-C6)alkylbenzoylureido, nitrobenzoylureido, (C1-C6)haloalkylbenzoylureido, (C1-C6)haloalkylhalobenzoylureido, halo(C6-C18)arylcarbomylacetamido, (C1-C6)alkoxy(C6-C18)arylcarbomylacetamido, (C1-C6)alkoxy(C6-C18)arylcarbamoyl(C3-C6)cycloalkylamido, halo(C6-C18)aryl(C3-C18)heteroarylcarbonylamino, (C3-C6)cycloalkyl(C3-C18)heteroarylcarbonylamino, (C1-C6)alkylamino(C6-C18)aryl(C3-C18)heteroarylcarbonylamino, halo(C1-C6)alkoxy(C6-C18)aryl(C3-C18) heteroarylcarbonylamino, (C1-C6)alkoxy(C6-C18)aryl(C3-C18)heteroarylcarbonylamino, (C1-C6)alkyl(C3-C18)heteroarylcarbonylamino, aryl(C3-C18)heteroarylcarbonylamino, (C1-C6)haloalkylhalo(C6-C18)aryl(C3-C6)heterocyclylcarbonylamino, (C1-C6)haloalkyl(C6-C18)aryl(C3-C18)heteroarylcarbonylamino, halo(C6-C18)aryl(C3-C18)heteroarylamido, (C1-C6)oxyalkyl(C3-C6)heterocyclylamido, (C1-C6)alkoxy(C1-C6)alkyl(C3-C18)heteroarylamido, (C6-C18)aryl(C3-C18)heteroarylamido, (C1-C6)alkyl(C1-C18)aryl(C3-C18)heteroarylamido, (C1-C6)haloalkyl(C6-C18)aryl(C3-C18)heteroarylamido, (C1-C6)alkyl(C3-C18)heteroarylamido, or (C1-C6)alkoxy(C6-C18)aryl(C3-C18)heteroarylamido; and Rf is hydrogen, (C1-C6)alkoxybenzoylureido, or halo(C6-C18)aryl(C3-C18)heteroarylamido.