HYDROSOLUBLE 3-ARYLIDENE-2-OXINDOLE DERIVATIVES AS TYROSINE KINASE INHIBITORS

摘要

Novel hydrosoluble 3-arylidene-2-oxindole derivatives, having tyrosine kinase inhibitor activity, encompassed by general formula (I), wherein m is zero, 1 or 2; A is a bicyclic ring chosen from tetralin, naphthalene, quinoline and indole; R<1> is hydrogen, C1-C6 alkyl or C2-C6 alkanoyl; one of R<2> and R<3> independently is hydrogen and the other is a substituent selected from: a C1-C6 alkyl group substituted by 1, 2 or 3 hydroxy groups; -SO3R<4> in which R<4> is hydrogen or C1-C6 alkyl unsubtituted or substituted by 1, 2 or 3 hydroxy groups; -SO2NHR<5> in which R<5> is as R<4> defined above or a -(CH2)n-N(C1-C6 alkyl)2 group in which n is 2 or 3; -COOR<6> in which R<6> is C1-C6 alkyl unsubtituted or substituted by phenyl or by 1, 2 or 3 hydroxy groups or phenyl; -CONHR<7> in which R<7> is hydrogen, phenyl or C1-C6 alkyl substituted by 1, 2 or 3 hydroxy groups or by phenyl; -NHSO2R<8> in which R<8> is C1-C6 alkyl or phenyl unsubtituted or substituted by halogen or by C1-C4 alkyl; -N(R<9>)2, -NHR<9> or -OR<9> wherein R<9> is C2-C6 alkyl substituted by 1, 2 or 3 hydroxy groups; -NHCOR<10>, -OOCR<10> or -CH2OOCR<10> in which R<10> is C1-C6 alkyl substituted by 1, 2 or 3 hydroxy groups; -NHCONH2; -NH-C(NH2)=NH; -C(NH2)=NH; -CH2NHC(NH2)=NH; -CH2NH2; -OPO(OH)2; -CH2OPO(OH)2; -PO(OH)2; or (a), (b), (c), or (d) group, wherein p is 1, 2 or 3 and Z is -CH2-, -O- or (e), in which R<11> is hydrogen or is as R<9> defined above; and the pharmaceutically acceptable salts thereof, are disclosed.