New 3-aminomethylidene-2-indolinone derivatives useful as kinase inhibitors and antiproliferative agents e.g. for treating viral infections, tumors, inflammation or autoimmune disease

摘要

3-(1-Amino-1-aryl-methylidene)-2-indolinone or thione derivatives (I) are new. 3-(1-Amino-1-aryl-methylidene)-2-indolinone or thione derivatives of formula (I) and their isomers and salts are new. X = O or S; R1, R4 = H or alkyl; R2 = H, halo, alkyl or NO2; R3 = phenyl or naphthyl (both optionally substituted by 1 or 2 of F, Cl, Br, alkyl, alkoxy, CN, CF3, NO2, NH2, mono- or dialkylamino, alkylsulfonylamino, aminoalkyl, mono- or dialkylaminoalkyl, alkanoylaminoalkyl and N-alkanoyl-N-alkylamino); R5 = phenyl or naphthyl both optionally substituted by one alkyl and further optionally substituted by (i) halo, alkyl, alkoxy, CN, NO2 or CF3, (ii) alkyl substituted by piperidino, hexamethyleneimino, morpholino or piperazino (where rings are all optionally substituted by alkyl, phenyl or phenylalkyl; and piperidino or hexamethyleneimino rings are further optionally substituted in the 3- or 4-position by OH, alkoxy or COOH), (iii) alkyl substituted by OH, alkoxy, COOH or CN, (iv) aminocarbonyl, amidino or guanidino (all optionally substituted by 1 or 2 alkyl), (v) piperidino, hexamethyleneimino, morpholino, piperazino or N-alkyl-piperazino, (vi) -CO-Q, (vii) NH2, 1-5C alkylamino, aminoalkyl, N-(alkylamino)-alkyl or di-(1-5C alkylamino)-alkyl (where all alkyl moieties are optionally substituted by CN, COOH, CONH2, mono- or di-alkylaminocarbonyl, 2-(dialkylamino)-ethylaminocarbonyl or 3-(dialkylamino)-propylcarbonyl or in the 2- or 3-position by OH, alkoxy, dialkylamino, piperidino, hexamethyleneimino, morpholino, piperazino or N-alkyl-piperazino; and N (where applicable) is optionally substituted by (1-5C) alkoxycarbonyl), (viii) 1-5C alkyl (optionally substituted (but not in the 1-position) by OH, alkoxy, NH2, or mono- or dialkylamino), (ix) alkylsulfonyl, amidosulfonyl or mono- or di-alkylaminoamidosulfonyl or (x) phenylalkylsulfonyl or phenylsulfonyl (both optionally substituted in the ring by F, Cl, Br, alkyl or alkoxy) and Q = H, OH, CF3, alkyl, alkoxyalkyl or dialkylamino; amino or alkylamino (both optionally substituted on N by carboxyalkyl, aminoalkyl or mono- or di-alkylaminoalkyl); piperidino, hexamethyleneimino, morpholino, piperazino, N-alkyl-piperazino, N-(phenylalkyl)-piperazino or 1-5C alkoxy; or alkyl (optionally substituted by COOH, OH, alkoxy, NH2, alkanoylamino, (1-5C) alkoxycarbonylamino, mono- or di-alkylamino, piperidino, hexamethyleneimino, morpholino, piperazino, N-alkyl-piperazino or N-(phenylalkyl)-piperazino). Any carboxy, amino or imino groups are optionally substituted by in vivo cleavable groups; Alkyl moieties have 1-3C and alkanoyl moieties 2-4C unless specified otherwise. An Independent claim is included for the preparation of (I).