NZ518489A - 6-position substituted indoline, production and use thereof as a medicament - Google Patents

Abstract

Disclosed are indolinone compounds of formula (I), wherein: X is O or S, R1 is H, alkoxycarbonyl or alkanoyl, R2 is carboxy, alkoxy-carbonyl, cycloalkoxy-carbonyl, aryloxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, or di-alkylaminocarbonyl, R3 is H, alkyl, cycloalkyl, trifluoromethyl, heteroaryl, phenyl or naphthyl, R4 is cycloalkyl or phenyl, R5 is H or alkyl, The compounds are used in the manufacture of medicaments for treating excessive or anomalous cell proliferation.

Description

New Zealand Paient Spedficaiion for Paient Number 518489 518489 71488pct.203 Boehringer Ingelheim Pharma KG D-55216 INGELHEIM Case 5/1275-Ro Foreign filing text 6-position substituted indolinone, production and use thereof as a medicament The present invention relates to new indolinones of general substituted in the 6 position, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof which have valuable properties.

The above compounds of general formula I wherein R1 denotes a hydrogen atom or a prodrug group have valuable pharmacological properties, in particular an inhibiting effect on various kinases, especially receptor tyrosine kinases such as VEGFR2, PDGFRa, PDGFRp, FGFR1, FGFR3, EGFR, HER2, IGF1R and HGFR, as well as complexes of CDK's (Cyclin Dependent Kinases) such as CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8 and CDK9 with their specific cyclins (A, Bl, B2, C, Dl, D2, D3, E, F, Gl, G2, H, I and K) and to viral cyclin (cf. L. Mengtao in J. Virology 71(3), 1984-1991 (1997)), and on the proliferation of cultivated human cells, in particular endothelial cells, e.g. in angiogenesis, but also on the proliferation of other cells, in particular tumour cells. formula 100572718 1 The other compounds of the above general formula I wherein Ri does not denote a hydrogen atom or a prodrug group are valuable intermediate products for preparing the abovementioned compounds.

The present invention thus relates to the above compounds of general formula I, whereby those compounds wherein R]_ denotes a hydrogen atom or a prodrug group have valuable pharmacological properties, pharmaceutical compositions containing the pharmacologically active compounds, the use thereof and processes for preparing them.

In the above general formula I X denotes an oxygen or sulphur atom, Ri denotes a hydrogen atom, a Ci-4-alkoxycarbonyl or C2-4~alkanoyl group, R2 denotes a carboxy group, a straight-chain or branched Ci-6-alkoxy-carbonyl group, a C4_7-cycloalkoxy-carbonyl or an aryloxycarbonyl group, a straight-chain or branched Ci-6-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a phenyl, heteroaryl, carboxy, Ci-3-alkoxy-carbonyl, aminocarbonyl, Ci-3-alkylamino-carbonyl or di-(Ci-3-alkyl)-aminocarbonyl group, a straight-chain or branched C2-6-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a chlorine atom or a hydroxy, Ci-3-alkoxy, amino, Ci_3-alkylamino or di-(Ci-3-alkyl)-amino group, ^uectuauwek1' office i QF NX- 2 1 DEC W* pcr.F-IVE.D an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2 position of the ethyl group by a hydroxy or C1_3-alkoxy group or, if R4 does not denote an aminosulphonyl-phenyl or N- (C1.5-alkyl)-C^-alkylaminocarbonyl-phenyl group, it may also denote a di-(C^-alkyl) -aminocarbonyl group, R3 denotes a hydrogen atom, a C^g-alkyl, C3_7-cycloalkyl, trifluoromethyl or heteroaryl group, a phenyl or naphthyl group, a phenyl or naphthyl group raono-or disubstituted by a fluorine, chlorine, bromine or iodine atom, by a trif luoromethyl, C-^j-alkyl or C^-alkoxy group, whilst in the event of disubstitution the substituents may be identical or different and wherein the abovementioned unsubstituted as well as the mono- and disubstituted phenyl and naphthyl groups may additionally be substituted by a hydroxy, hydroxy-Cx.3-alkyl or C^-alkoxy-C^-,-alkyl group, by a cyano, carboxy, carboxy-C^-alkyl, C^-alkoxycarbonyl, aminocarbonyl, C^-alkylamino-carbonyl or di-(C1.3-alkyl)-aminocarbonyl group, by a nitro group, by an amino, C^-alkylamino, di-(C^-alkyl) -amino or amino-C^-j-alkyl group, by a C1.3-alkylcarbonylamino, N- (C^-alkyl) -C1.3-alkyl-carbonylamino, C1_3-alkylcarbonylamino-C1.3-alkyl, N- (C-^-j-alkyl) -C1_3-alkylcarbonylamino-C1_3-alkyl, C^-alky!-sulphonylamino, C^-alkylsulphonylamino-C^-alkyl, N- (C^-alkyl) -C1.3-alkylsulphonylamino-C1.3-alkyl or aryl--alkylsulphonylamino group, by a cycloalkylamino, cycloalkyleneimino, cyclo-alkyleneiminocarbonyl, cycloalkyleneimino-C^-alkyl, cycloalkyleneiminocarbonyl-C1_3-alkyl or cycloalkyleneiminosulphonyl-C^j-alkyl group having 4 to 7 ring members in each case, whilst in each case the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, b^ a sulphinyl, sulphonyl, -NH or -N(C1_3-alkyl) group, or by a heteroaryl or heteroaryl-C^-alkyl group, R4 denotes a C3_7-cycloalkyl group, whilst the methylene group in the 4 position of a 6- or 7-membered cycloalkyl group may be substituted by an amino, Cj.-j-alkylamino or di-(C^-alkyl) -amino group or replaced by an -NH or -N (C^-alkyl) group, or a phenyl group substituted by the group R6, which may additionally be mono- or disubstituted by fluorine, chlorine, bromine or iodine atoms, by C^g-alkyl, trifluoromethyl, hydroxy, C1_3-alkoxy, carboxy, C^-alkoxycarbonyl, amino, acetylamino, C^-alkyl-sulphonylamino, aminocarbonyl, Ci.3-alkyl-aminocarbonyl, di - (-alkyl) -aminocarbonyl, aminosulphonyl, C^-alkyl-aminosulphonyl, di-(C^-alkyl)-aminosulphonyl, nitro or cyano groups, wherein the substituents may be identical or different and wherein Rs denotes a hydrogen, fluorine, chlorine, bromine or iodine atom, a cyano, nitro, amino, C^j-alkyl, C3_7-cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl group, the group of formula K N—^o H u / wherein the hydrogen atoms bound to a nitrogen atom may in each case be replaced independently of one another by a C x _ 3 — a 1 ky 1 group, a C^-alkoxy group, a C1_3-alkoxy-C1.3-alkoxy, phenyl - -alkoxy, amino-C2_3-alkoxy, Cx_ 3 - alkyl amino -C2.3- alkoxy, di- (C^-alkyl) -amino-C2_3-alkoxy, phenyl-C1.3-alkylamino-C2_3-alkoxy, N- (C1_3-alkyl) -phenyl-C-L.-j-alkylamino-C^-alkoxy, C5_7-cycloalkyleneimino-C2_3-alkoxy or C^-j-alkylmercapto group, a carboxy, Ci^-alkoxycarbonyl, aminocarbonyl, C±_3-alkyl-amino-carbonyl, N- (C^s-alkyl) -C1_3-alkylaminocarbonyl, phenyl - - alkyl amino - carbonyl, N- (C^.,-alkyl) -phenyl-C^-alkylamino-carbonyl, piperazinocarbonyl or N- (Cx.3-alkyl) -piperazinocarbonyl group, a C^-alkylaminocarbonyl or N- (C^-alkyl) -Ci.j-alkylaminocarbonyl group wherein an alkyl moiety is substituted by a carboxy or C^-alkoxycarbonyl group or in the 2 or 3 position by a di- (C^-alkyl) -amino, piperazino, N- (C1.3-alkyl) -piperazino or a 4- to 7-membered cycloalkyleneimino group, a C3_7-cycloalkyl-carbonyl group, wherein the methylene group in the 4 position of the 6- or 7-membered cycloalkyl moiety may be substituted by an amino, C^-alkylamino or di- (C^-alkyl) -amino group or replaced by an -NH or -N(C^-j-alkyl) group, a 4- to 7-membered cycloalkyleneimino group wherein a methylene group linked to the imino group may be replaced by a carbonyl or sulphonyl group or the cycloalkylene moiety may be fused to a phenyl ring or one or two hydrogen atoms may each be replaced by a C^-alkyl group and/or in each case the methylene group in the 4 position of a 6-or 7-membered cycloalkyleneimino group may be substituted by a carboxy, C^-alkoxycarbonyl, aminocarbonyl, C^j-alkylaminocarbonyl, di- (C1_3-alkyl) -aminocarbonyl, phenyl-C1_3-alkylamino or N- (C1_3-alkyl) -phenyl--alkylamino group or may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (C^-alkyl), -N(phenyl), -N (C^j-alkyl-carbonyl) or -N(benzoyl) group, a C^ — alkyl group substituted by the group R7, wherein R7 denotes a C3„7-cycloalkyl group, whilst the methylene group in the 4 position of a 6- or 7-membered cycloalkyl group may be substituted by an amino, C^-alkylamino or di- (C^-alky!) -amino group or replaced by an -NH or -N(G^-alkyl) group or in a 5- to 7-membered cycloalkyl group a ~(CH2)2 group may be replaced by a -CO-NH group, a -(CH2)3 group may be replaced by a -NH-CO-NH or -CO-NH-CO group or a -(CH2)4 group may be replaced by a -NH-CO-NH-CO group, whilst in each case a hydrogen atom bound to a nitrogen atom may be replaced by a -alkyl group, an aryl or heteroaryl group, a hydroxy or C1_3-alkoxy group, an amino, C^-alkylamino, di-(C^-alkyl) -amino, phenylamino, N-phenyl-C^-alkyl-amino, phenyl-C1_3-alkyl-amino, N- (C1_3-alkyl) -phenyl-C-^-alkylamino or di-(phenyl-C1_3-alkyi) -amino group, an co-hydroxy-C2_3-alkyl-amino, N-(C1_3-alkyl)-co-hydroxy-C2_3-alkyl-amino, di- (co-hydroxy-C2_3-alkyl) -amino, di- (co — alkoxy) -C2_3-alkyl) -amino or N- (dioxolan- 2-yl) — Cx_3 — alkyl — amino group, a C1.3-alkylcarbonylamino-C2_3-alkyl-amino or C-L.-j-alkylcarbonylamino-C-j^-alkyl-N- (C^-alkyl) -amino group, a C1-3 — alky 1 sulphony 1 amino, N- (C^-alkyl)-C^-j-alkyl-sulphonylamino, C^-alkylsulphonylamino-Cj^-alkyl-amino or C1_3-alkylsulphonylamino-C2_3-alkyl-N- (C^-alkyl) -amino group, a hydroxycarbonyl-C^-alkylamino or N-(C^.,-alkyl) -hydroxycarbonyl - Cx.3 - alkyl - amino group, a guanidino group wherein one or two hydrogen atoms may each be replaced by a C^-alkyl group, a group of formula -N(R8)-CO-(CH2)n-R9 (II), wherein R8 denotes a hydrogen atom or a Cx_3-alkyl group, n denotes one of the numbers 0, 1, 2 or 3 and R9 denotes an amino, Cx_4-alkylamino, di- (Cx_4-alkyl)-amino, phenylamino, N- (Cx_4-alkyl) -phenylamino, benzylamino, N- (Cx_4-alkyl) -benzylamino or Cx_4-alkoxy group, a 4- to 7-membered cycloalkyleneimino group, whilst in each case the methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N(CX_3-alkyl) , -N(phenyl), -N (C^-alkyl-carbonyl) or -N(benzoyl) group, or, if n denotes one of the numbers 1, 2 or 3, it may also denote a hydrogen atom, a group of formula -N(R10) - (CH2)m- (C0)o-Rn (III), wherein R10 denotes a hydrogen atom, a Cx_3-alkyl group, a Cx_3-alkylcarbonyl, arylcarbonyl, phenyl-Cx_3-alkyl-carbonyl, Cx_3-alkylsulphonyl, arylsulphonyl or phenyl - - alkyl sulphonyl group, m denotes one of the numbers 1, 2, 3 or 4, o denotes the number 1 or, if m denotes one of the numbers 2, 3 or 4, o may also denote the number 0 and RX1 denotes an amino, Cx_4-alkylamino, di - (C1_4 — alkyl) -amino, phenylamino, N- (Cx_4-alkyl) -phenylamino, benzylamino, N-(Cx_4-alkyl)-benzylamino, Cx.4-alkoxy or C1_3-alkoxy-C1.3-alkoxy group, a di- (C^-alkyl) -amino-Cj.j-alkylamino group optionally substituted in the 1 position by a C^-alkyl group or a 4- to 7-membered cycloalkyleneimino group, wherein the cycloalkylene moiety may be fused to a phenyl ring or in each case the methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (C1_3-alkyl)', -N(phenyl), -N (C^-alkyl-carbonyl) or -N(benzoyl) group, a C4_7-cycloalkylamino, C4_7-cycloalkyl-C1_3-alkylamino or C4_7-cycloalkenylamino group wherein position 1 of the ring is not involved in the double bond and wherein the abovementioned groups may each additionally be substituted at the amino-nitrogen atom by a Cs_7-cycloalkyl, C2„4-alkenyl or C^-alkyl group, a 4- to 7-membered cycloalkyleneimino group, wherein the cycloalkylene moiety may be fused to a phenyl group or to an oxazolo, imidazolo, thiazolo, pyridino, pyrazino or pyrimidino group optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, Cj^-alkyl, C^-alkoxy or amino group, and/or one or two hydrogen atoms may each be replaced by a Ci.j-alkyl, Cs_7-cycloalkyl or phenyl group and/or the methylene group in the 3 position of a 5-membered cycloalkyleneimino group may be substituted by a hydroxy, hydroxy-C^-j-alkyl, C1.3-alkoxy or C1_3-alkoxy—C^- alkyl group, the methylene group in the 3 or 4 position of a 6- or 7-membered cycloalkyleneimino group may in each case be substituted by a hydroxy, hydroxy-C1_3-alkyl, C^-alkoxy, C^.j-alkoxy-C^-alkyl, carboxy, C1_4-alkoxycarbonyl, aminocarbonyl, C1_3-alkylaminocarbonyl, di- (C1_3-alkyl) -aminocarbonyl, phenyl-C1.3-alkylamino or N- (C^.-j-alkyl) -phenyl-C^-alkyl -amino group or may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (C^-alkyl-), -N(phenyl), -N(phenyl-Cj^-alkyl-) , -N(C^-alkyl-carbonyl-) , -N (Ci.4-hydroxy-carbonyl-) , -N (C^- alkoxy-carbonyl -) , -N (benzoyl-) or -N (phenyl-C^-alkyl-carbonyl -) group, wherein a methylene group linked to an imino-nitrogen atom of the cycloalkyleneimino group may be replaced by a carbonyl or sulphonyl group or in a 5-to 7-membered monocyclic cycloalkyleneimino group or a cycloalkyleneimino group fused to a phenyl group the two methylene groups linked to the imino-nitrogen atom may each be replaced by a carbonyl group, or R6 denotes a C^-alkyl group which is substituted by a carboxy, C^-alkoxycarbonyl, aminocarbonyl, C^-alkylaminocarbonyl or di- (C^-alkyl) -aminocarbonyl group or by a 4- to 7-membered cycloalkyleneiminocarbonyl group, an N- (C1_3-alkyl) -C2.4-alkanoylamino group which is additionally substituted in the alkyl moiety by a carboxy or C^-alkoxycarbonyl group, a group of formula -N(R12)-CO-(CH2)p-Ri3 (IV), wherein R12 denotes a hydrogen atom, a C^-alkyl or C3_7-cycloalkyl group or a C^-alkyl group terminally substituted by a phenyl, heteroaryl, trif luoromethyl, hydroxy, C1_3-alkoxy, aminocarbonyl, C-^-alkylamino-carbonyl, di-(Cx.4-alkyl) -amino - carbonyl, -alkyl-carbonyl, C^-alkyl-sulphonyl-amino, N- (C^-alkyl) -C^-alkyl-sulphonylamino, C1-3-alkyl-aminosulphonyl or di- (C-^-alkyl) -aminosulphonyl group and p denotes one of the numbers 0, 1, 2 or 3 and R13 assumes the meanings of the abovementioned group R7, or, if p denotes one of the numbers 1, 2 or 3, it may also denote a hydrogen atom, a group of formula -N(R14)-(CH2)q-(CO)r-R15 (V), wherein R14 denotes a hydrogen atom, a Cx_4-alkyl group, a 0^3-alkylcarbonyl, arylcarbonyl, phenyl-C^-alkylcarbonyl, heteroarylcarbonyl, heteroaryl-Cx_3-alkylcarbonyl, C^-alkylsulphonyl, arylsulphonyl, phenyl-C^-alkylsulphonyl, heteroarylsulphonyl or heteroaryl - C1_3 - alkyl - sulphonyl group, q denotes one of the numbers 1, 2, 3 or 4, r denotes the number 1 or, if q is one of the numbers 2, 3 or 4, it may also denote the number 0 and R15 assumes the meanings of the abovementioned group R7, a group of formula -N(R16)-S02-Riv (VI), wherein R16 denotes a hydrogen atom or a C^-alkyl group optionally terminally substituted by a cyano, trifluoromethyl-carbonylamino or N- (C1_3-alkyl) -trifluoromethyl-carbonyl-amino group and R17 denotes a Cx.3-alkyl group, an amino group substituted by a di-(C^-alkyl) -amino-C^-alkyl-carbonyl or di-(C^-alkyl) -amino -C^-j- alkyl -sulphonyl group and a di - (C^- alkyl) -aminocarbonyl-C^-alkyl group, or an N- (C^-alkyl) -C^s-alkylsulphonylamino or N- (C^-alkyl)-phenylsulphonylamino group wherein the alkyl moiety is additionally substituted by a cyano or carboxy group, wherein all the single-bonded or fused phenyl groups contained in the groups mentioned under R6 may be mono- or disubstituted by fluorine, chlorine, bromine or iodine atoms, by C^-alkyl, trifluoromethyl, hydroxy, C^-alkoxy, carboxy, Cx_3-alkoxycarbonyl, aminocarbonyl, Cj^-alkylamino-carbonyl, di- (C1_4-alkyl) - amino-carbonyl, aminosulphonyl, Cx_3 - alkyl - aminosulphonyl, di- (C1.3-alkyl) -aminosulphonyl, C^-alkyl-sulphonylamino, nitro or cyano groups, wherein the substituents may be identical or different, or two adjacent hydrogen atoms of the phenyl groups may be replaced by a methylenedioxy group, and R5 denotes a hydrogen atom or a C^-alkyl group, wherein by an aryl group is meant a phenyl or naphthyl group optionally mono- or disubstituted by a fluorine, chlorine, bromine or iodine atom, by a cyano, trifluoromethyl, nitro, carboxy, aminocarbonyl, C^-alkyl or C^-alkoxy group and by a heteroaryl group is meant a monocyclic 5- or 6-membered heteroaryl group optionally substituted by a C^-alkyl group in the carbon skeleton, wherein the 6-membered heteroaryl group contains one, two or three nitrogen atoms and the 5-membered heteroaryl group contains an imino group optionally substituted by a C1.3-alkyl or phenyl-C1_3-alkyl group, an oxygen or sulphur atom or an imino group optionally substituted by a C^-alkyl or phenyl -C^- alkyl group or an oxygen or sulphur atom and additionally a nitrogen atom or an imino group optionally substituted by a C^-alkyl or phenyl-C^-alkyl group and two nitrogen atoms, and moreover a phenyl ring may be fused to the abovementioned monocyclic heterocyclic groups via two adjacent carbon atoms and the bonding takes place via a nitrogen atom or via a carbon atom of the heterocyclic moiety or a fused phenyl ring, some or all of the hydrogen atoms in the abovementioned alkyl and alkoxy groups or in the alkyl moieties contained in the above-defined groups of formula I optionally being replaced by fluorine atoms, the saturated alkyl and alkoxy moieties with more than 2 carbon atoms which are present in the groups defined hereinbefore also include the branched isomers thereof, such as for example the isopropyl, tert.butyl, isobutyl group, unless, otherwise stated, and additionally the hydrogen atom of any carboxy group present or a hydrogen atom bound to a nitrogen atom, e.g. a hydrogen atom of an amino, alkylamino or imino group or a saturated N-heterocycle such as the piperidinyl group, may each be replaced by a hydroxy group, an acyl group such as the benzoyl or pyridinoyl group or a Ci-i6~alkanoyl group such as the formyl, acetyl, propionyl, butanoyl, pentanoyl or hexanoyl group, an allyloxycarbonyl group, a Ci-i6-alkoxycarbonyl group such as the methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert.butoxycarbonyl, pentoxycarbonyl, hexyloxycarbonyl, octyloxycarbonyl, nonyloxycarbonyl, decyloxycarbonyl, undecyloxycarbonyl, dodecyloxycarbonyl or hexadecyloxycarbonyl group, a phenyl-Ci-6-alkoxycarbonyl group such as the benzyloxycarbonyl, phenylethoxycarbonyl or phenylpropoxycarbonyl group, a Ci-3-alkylsulphonyl-C2-4~alkoxycarbonyl, Ci-3-alkoxy-C2-4~alkoxy-C2-4-alkoxycarbonyl or ReC0-0-(RfCRg)-0-C0 group wherein Re denotes a Ci-s-alkyl, C5-7-cycloalkyl, phenyl or phenyl- Ci_3-alkyl group, INTELLECTUAL PROPERTY OFFICE OF N.Z. 2 1 DEC 2004 RECEIVED Rf denotes a hydrogen atom, a Ci-3-alkyl, Cs-7-cycloalkyl or phenyl group and Rg denotes a hydrogen atom, a Ci-3-alkyl or ReC0-0-(RfCRh) -0 group wherein Re and Rf are as hereinbefore defined and Rh is a hydrogen atom or a C1-3 alkyl group, wherein additionally the amino group may be a phthalimido group, whilst the abovementioned ester groups may also be used as a group which can be converted in vivo into a carboxy group.

One sub-group of compounds of general formula I which deserves special mention comprises those wherein X, Ri and R3 to R5 are as hereinbefore defined and R2 denotes a straight-chain or branched Ci-6-alkoxy-carbonyl group, a C4-7~cycloalkoxycarbonyl or a aryloxycarbonyl group, a straight-chain or branched Ci-6-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a phenyl, heteroaryl, carboxy, Ci-3-alkoxycarbonyl, aminocarbonyl, Ci-3-alkylaminocarbonyl or di-(Ci-3-alkyl)-aminocarbonyl group, a straight-chain or branched C2-6~alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a chlorine atom or a hydroxy, Ci-3-alkoxy, amino, Ci-3-alkylamino or di-(Ci-3-alkyl)-amino group, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof.

A second sub-group of compounds of general formula I which deserves special mention comprises those wherein intellectual property OFFICE OF N.Z. - 1 MAR 2005 X, Rx and R3 to R5 are as hereinbefore defined and R2 denotes an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2 position of the ethyl group by a hydroxy or Cx_3-alkoxy group or, if R4 does not denote an aminosulphonyl-phenyl or N- (Cx.5-alkyl) -Cx_3-alkylaminocarbonyl-phenyl group, R2 may also denote a di-(Cx_2-alkyl) -aminocarbonyl group, 1 the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof.

A third sub-group of compounds of general formula I which deserves special mention comprises those wherein X, Rx to R3 and R5 are as hereinbefore defined and R4 denotes an R7- (Cx.4-alkyl) -phenyl group, wherein R7 denotes an amino, Cx_7-alkylamino, di- (Cx_7-alkyl) -amino, phenylamino, N-phenyl-Cx.3-alkyl-amino, phenyl-Cx_3-alkyl -amino, N- (Cx_3-alkyl) -phenyl-Cx_3-alkyl amino or di - (phenyl-Cx_3-alkyl) -amino group, or a phenyl group substituted by the group of formula -N(R12)-CO-(CH2)p-Ri3 (IV), wherein R12, p and R13 are as hereinbefore defined, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof.

Preferred compounds of general formula I are those wherein Rx and R3 are as hereinbefore defined and X denotes an oxygen atom, R2 denotes a carboxy group, a straight-chain or branched C^.g-alkoxy-carbonyl group, a C5_7-cycloalkoxycarbonyl or a phenoxycarbonyl group, / a straight-chain or branched C^-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a phenyl, heteroaryl, carboxy, C^-alkoxycarbonyl, aminocarbonyl, C^-alkylaminocarbonyl or di-(C^-alkyl)-aminocarbonyl group, a straight-chain or branched C2_3-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a chlorine atom, by a hydroxy, C^-alkoxy, amino, C^-alkylamino or di- (^.3-alkyl) -amino group, an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2 position of the ethyl group by a hydroxy or C-^-alkoxy group or, if R4 does not denote an aminosulphonyl-phenyl or N- (C^g-alkyl) -C^-alkylaminocarbonyl-phenyl group, it may also denote a di - alkyl) -aminocarbonyl group, R4 denotes a C3.7-cycloalkyl group, whilst the methylene group in the 4 position of a 6- or 7-membered cycloalkyl group may be substituted by an amino, C-^-alkylamino or di-(C^-alkyl) -amino group or replaced by an -NH or -N(C1.3-alkyl) group, or a phenyl group substituted by the group R6, which may additionally be mono- or disubstituted by fluorine, chlorine or bromine atoms, by -alkyl, trif luoromethyl, hydroxy, C^-alkoxy, carboxy, C1_3-alkoxycarbonyl, amino, acetylamino, aminocarbonyl, Cx_3 - alkyl - aminocarbonyl, di-(Cx.3-alkyl)-aminocarbonyl, nitro or cyano groups, wherein the substituents may be identical or different and wherein R6 denotes a hydrogen, fluorine, chlorine, bromine or iodine atom, a cyano, nitro, amino, C^g-alkyl, C3_7-cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl group, the group of formula wherein a hydrogen atom bound to the nitrogen atom may be replaced by a C1.3-alkyl group, a C1.3-alkoxy group, an amino-C2_3-alkoxy, C^-alkylamino-C2_3-alkoxy, di- (C^-alky!) - amino-C2.3-alkoxy, phenyl-C^j-alkylamino-Cj^-alkoxy, N- (C^-alkyl) -phenyl-C1-3 - alkyl amino - C2.3 - alkoxy, pyrrol idino - C2_3 - alkoxy, piperidino-C2_3-alkoxy or C-^-j-alkylmercapto group, a carboxy, Cx.4-alkoxycarbonyl, aminocarbonyl, Cx_3-alkyl-amino-carbonyl, phenyl-C^-alkylamino-carbonyl or N- (Cj.-j-alkyl) -phenyl-^.3-alkylamino-carbonyl group, a C3_7-cycloalkyl-carbonyl group, wherein the methylene group in the 4 position of the 6- or 7-membered cycloalkyl moiety may be replaced by an -NH or -N(C-L.-j-alkyl) group, 0 CH a 4- to 7-membered cycloalkyleneimino group, wherein a methylene group linked to the imino group may be replaced by a carbonyl or sulphonyl group or one or two hydrogen atoms may each be replaced by a Cx_3 — alkyl group and/or in each case th£ methylene group in the 4 position of a 6-or 7-membered cycloalkyleneimino group may be substituted by a carboxy, C^-alkoxycarbonyl, aminocarbonyl, C-^-alkylaminocarbonyl, di - (C^-alkyl) -aminocarbonyl, phenyl-Cj.3-alkylamino or N- (C^-alkyl) -phenyl-C^.3-alkylamino group or may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH or -N (C-^-alkyl) group, a C^-alkyl group terminally substituted by the group R7, wherein R7 denotes a Cs_7-cycloalkyl group, whilst the methylene group in the 4 position of a 6- or 7-membered cycloalkyl group may be replaced by an -NH or -N(C1_3-alkyl) group or in a 5- to 7-membered cycloalkyl group a -(CH2)2 group may be replaced by a -CO-NH group, a -(CH2)3 group may be replaced by a -NH-CO-NH- or a -(CH2)4 group may be replaced by a -NH-CO-NH-CO group, whilst in each case a hydrogen atom bound to a nitrogen atom may be replaced by a C1-3 — alky 1 group, a phenyl or heteroaryl group, a hydroxy or C^-alkoxy group, an amino, C^g-alkylamino, di-(C^-alkyl) -amino, phenylamino, N-phenyl--alkyl-amino, phenyl-C^j-alkylamino, N- (C^-alkyl) -phenyl-C^-alkylamino or di-(phenyl-C^-alkyl)-amino group, a co-hydroxy-C2_3-alkyl-amino, N- (C^-alkyl) -co-hydroxy- I -C2_3-alkyl-amino, di- (co-hydroxy-C2_3-alkyl) -amino, di- ( One subgroup of preferred compounds of general formula I deserving special mention comprises those wherein R2 denotes a straight-chain or branched C1_6-alkoxy-carbonyl group, a C5_7-cycloalkoxycarbonyl or a phenoxycarbonyl group, a straight-chain or branched C^-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a phenyl-carboxy, C^-alkoxycarbonyl, aminocarbonyl, C1_3-alkylaminocarbonyl or di - (C^-alkyl) -aminocarbonyl group, t a straight-chain or branched C2.3-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a hydroxy, C^-alkoxy, amino, C^-j-alkylamino or di- (C^-alkyl) -amino group, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof.

A second sub-group of preferred compounds of general formula I deserving special mention comprises those wherein X, Rx and R3 to R5 are as hereinbefore defined and R2 denotes an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2 position of the ethyl group by a hydroxy or C^-alkoxy group or, if R4 does not denote an aminosulphonyl-phenyl or N- (C^-alkyl) -C^-j-alkylaminocarbonyl-phenyl group, R2 may also denote a di - (C^-alkyl)-aminocarbonyl group, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof.

A third sub-group of preferred compounds of general formula I deserving special mention comprises those wherein X, R-l to R3 and R5 are as hereinbefore defined and R4 denotes an R7-(n-C^-alkyl)-phenyl group, wherein Rv denotes an amino, C^-alkylamino, di- (C^-alkyl) -amino, phenylamino, N-phenyl-C^-alkyl-amino, phenyl-C^-alkyl-amino, N- (C1.3-alkyl) -phenyl-C^-alkylamino or di-(phenyl-Cj.j-alkyl) -amino group, or a phenyl group substituted by the group of formula -N(R12)-CO-(CH2)p-Ri3 (IV), wherein R12, p and R13 are as hereinbefore defined, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof.

Particularly preferred compounds of general formula I are those wherein X denotes an oxygen atom, Rx denotes a hydrogen atom, R2 denotes a carboxy group, a straight-chain or branched C^-alkoxycarbonyl group or a phenoxycarbonyl group, a straight-chain or branched C^-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a phenyl, carboxy, C^-alkoxycarbonyl, aminocarbonyl, C-L.-j-alkylaminocarbonyl or di-(C^-alkyl) -aminocarbonyl group, a straight-chain or branched C2_3-alkoxy-carbonyl group which is terminally substituted in the alkyl moiety by a hydroxy, C^-alkoxy, amino, C-^-alkylamino or di-(C^-alkyl) -amino group, an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2 position of the ethyl group by a hydroxy or C1_3-alkoxy group or, if R4 does not denote an aminosulphonyl-phenyl or N- (Cj.g-alkyl) -Ci_3-alkylaminocarbonyl-phenyl group, it may also denote a di - (C^-alkyl)-aminocarbonyl group, R3 denotes a C^-alkyl group or a phenyl group which may be substituted by a fluorine, chlorine or bromine atom, by a trif luoromethyl, C^-alkyl, hydroxy or C^-alkoxy group, R4 denotes a C5.6-cycloalkyl group, wherein the methylene group in position 4 of the cyclohexyl group may be substituted by an amino, C1.3-alkylamino or di- (C1.3-alkyl) -amino group or replaced by an -NH or -N(C^-alkyl) group, a phenyl group, a phenyl group disubstituted by C1_3-alkyl, C^-alkoxy or nitro groups, wherein the substituents may be identical or different, or a phenyl group substituted by the group R6, which may additionally be substituted by a fluorine, chlorine or bromine atom or by an amino or nitro group, wherein R6 denotes a fluorine, chlorine or bromine atom, a C^-j-alkyl, C^-alkoxy, nitro, amino or Cs_6-cycloalkyl group, a pyrrolyl, pyrazolyl, imidazolyl, triazolyl or tetrazolyl group bound via a carbon atom, wherein the abovementioned heteroaromatic groups in the carbon skeleton may be substituted by a C^-alkyl group or a hydrogen atom bound to a nitrogen atom may be replaced by a C^-alkyl or phenyl-C^-alkyl group, the group of formula a carboxy, C1.4-alkoxycarbonyl, phenyl-C1.3-alkylamino-carbonyl or C5_7-cycloalkyl-carbonyl group, a 5 or 6-membered cycloalkyleneimino group, wherein the methylene group in position 4 of the piperidino group may be replaced by an oxygen or sulphur atom, by an -NH or -N (C1_3-alkyl) group, an unbranched C^-alkyl group terminally substituted by the group R7, wherein R7 denotes a C5.7-cycloalkyl group, wherein in a 5 or 6-membered cycloalkyl group a ~(CH2)2 group may be replaced by a -CO-NH group, a -(CH2)3 group may be replaced by an -NH-CO-NH- or a -(CH2)4 group may be replaced by an -NH-CO-NH-CO group, whilst in each case a hydrogen atom bound to a nitrogen atom may be replaced by a Cx.3-alkyl group, a phenyl or pyridinyl group or a pyrrolyl, pyrazolyl, imidazolyl or triazolyl group bound via a carbon or nitrogen atom, wherein the abovementioned heteroaromatic groups in the carbon skeleton may be substituted by a 0 C^.3-alkyl group or a hydrogen atom bound to a nitrogen atom may be replaced by a Cx.3-alkyl group, a hydroxy or -alkoxy group, an amino, C^-alkylamino, di- (C^-alkyl) -amino, phenylamino, N-phenyl--alkylamino, phenyl-G^3-alkylamino or N- (C^-alkyl) -phenyl-C^-alkylamino group, a co-hydroxy-C2_3-alkyl-amino, N- (C^.-j-alkyl) - co - hydroxy-C2_3-alkyl amino, di- (co-hydroxy-C2_3-alkyl) -amino or di- (©- (C^-alkoxy) -C2_3-alkyl) -amino group, a C^-alkylcarbonylamino-G^-alkyl-amino or G^-alkylcarbonylamino-G^-alkyl-N- (C^-alkyl) -amino group, a C^-alkylsulphonylamino, N-(C^-alkyl)-C^-alkyl sulphonyl amino, Cx_3-alkylsulphonylamino--C2.3-alkylamino or C1.3-alkylsulphonylamino--C2.3-alkyl-N- (C^-alkyl) -amino group, a hydroxycarbonyl-C^-alkylamino or N- (C^-alkyl) -hydroxycarbonyl-C^-alkyl-amino group, a guanidino group wherein a hydrogen atom may be replaced by a C1_3_alkyl group, a group of formula -N(R8)-CO-(CH2)n-R9 (ID/ wherein R8 denotes a hydrogen atom or a C^-alkyl group, n denotes one of the numbers 0, 1, 2 or 3 and R9 denotes an amino, C^-alkylamino, di- (C^-alkyl) -amino or C1_4-alkoxy group, a 5- or 6-membered cycloalkyleneimino group, wherein the methylene group in position 4 of the piperidino group may be replaced by an -NH, -N (C1_3-alkyl) or -N (^.3-alkyl-carbonyl) group, or, if n denotes one of the numbers 1, 2 or 3, R9 may also denote a hydrogen atom, a group of formula -N (R10) - (CH2) m- (CO) q-Rh (III), wherein R10 denotes a hydrogen atom or a C^j-alkyl group, m denotes one of the numbers 1, 2 or 3, o denotes the number 1 or, if m is one of the numbers 2 or 3, o may also denote the number 0 and RX1 denotes an amino, C^-alkylamino, di- (C1.3-alkyl) -amino, C^-alkoxy or methoxy-C^-alkoxy group or a 5- or 6-membered cycloalkyleneimino group, wherein the methylene group in position 4 of the piperidino group may be replaced by an -NH, -N (C-L.j-alkyl) or -N (C^-alkyl-carbonyl) group, an azetidino, pyrrolidino, piperidino, 2,6-dimethyl-piperidino, 3,5-dimethyl-piperidino or azepino group, wherein the methylene group in position 3 of the pyrrolidine group may be substituted by a hydroxy group, the methylene group in position 4 of the piperidino group may be substituted by a hydroxy, hydroxy-C1_3-alkyl or C^-alkoxy group or may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (C1.3-alkyl) , -N (C1_3-alkyl-carbonyl), -N(benzoyl) or -N(phenyl-C^-alkyl-carbonyl) group, wherein a methylene group linked to an imino-nitrogen atom of the pyrrolidino, piperidino or piperazino group may be replaced by a carbonyl group, or R6 denotes a straight-chain C^-alkyl group which is terminally substituted by a carboxy or C^-alkoxy-carbonyl group, a group of formula -N(R12)-CO-(CH2)p-Ri3 (IV), wherein R12 denotes a hydrogen atom, a C^-alkyl or phenyl-C^-alkyl group, p denotes one of the numbers 0, 1 or 2 and R13 denotes an amino, C.^,,-alkylamino, di - (C^-alkyl) -amino, benzylamino, N- (C^-alkyl)-benzylamino, C1„3-alkoxy-C1„3-alkylamino, N- (C^-alkyl) - Cj.j-alkoxy-C-L.j-alkylamino, di- (2-methoxy-ethyl) -amino, di-(co-hydroxy-C2.3-alkyl)-amino or aminocarbonyl-methyl-N-(methyl)-amino group, a pyrrolyl, pyrazolyl or imidazolyl group bound via a nitrogen atom and optionally substituted by a C1_3-alkyl group, a pyrrolidino, piperidino, morpholino, thiomorpholino or a piperazino group optionally substituted in the 4 position by a Ci.j-alkyl, phenyl-C1.3-alkyl, C1.3-alkylcarbonyl or C1_4-alkoxycarbonyl group or, if n denotes the number 1 or 2, it may also denote a hydrogen atom, a group of formula -N(R14)-(CH2)q-(CO)r-R15 (V), wherein R14 denotes a hydrogen atom, a -alkyl, C^-alkyl-carbonyl, phenylcarbonyl, phenyl-C^-alkylcarbonyl, furyl-carbonyl, pyridinyl-carbonyl, furyl-C-^-alkylcarbonyl, pyridinyl-C1_3-alkylcarbonyl, C^-alkylsulphonyl, phenyl sulphonyl or phenyl-C1.3-alkylsulphonyl group, q denotes one of the numbers 1, 2 or 3, r denotes the number 1 or, if q is one of the numbers 2 or 3, it may also denote the number 0 and R1S denotes an amino, C-^-alkylamino, di-(Cx_4-alkyl)-amino, phenylamino, N- {C1_i-alkyl) -phenylamino, benzylamino or N-(C^—alkyl)-benzylamino group, or a group of formula -N (Rig) ~SC>2"R-17 (VI), wherein R16 denotes a hydrogen atom or a C^-alkyl group optionally terminally substituted by a cyano, trifluoromethyl-carbonylamino or N- (C1.3-alkyl) -trifluoromethyl-carbonyl-amino group and R17 denotes a C1_3-alkyl group, wherein all the single-bonded or fused phenyl groups contained in the groups mentioned under Rs may be substituted by a fluorine, chlorine or bromine atom, by a methyl, trifluoromethyl, methoxy, nitro or cyano group and R5 denotes a hydrogen atom, wherein a hydrogen atom bound to a nitrogen atom in the abovementioned groups may be replaced by an acetyl or tert.butoxycarbonyl group, the carboxy groups contained in the abovementioned groups may also be present in the form of the tert.butoxycarbonyl precursor group and the saturated alkyl and alkoxy moieties contained in the abovementioned groups, which contain more than 2 carbon atoms, may be straight-chain or branched, unless otherwise stated, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof.

One subgroup of particularly preferred compounds of general formula I deserving special mention comprises those wherein X, R1( R3 and R5 are as hereinbefore defined, R2 denotes a straight-chain or branched C^-alkoxycarbonyl group or a phenoxycarbonyl group, a straight-chain or'branched C1_3-alkoxycarbonyl group, which is terminally substituted in the alkyl moiety by a phenyl-carboxy, C^-alkoxycarbonyl, aminocarbonyl, C1_3-alkylaminocarbonyl or di - (C^-alkyl) -aminocarbonyl group, or a straight-chain or branched C2.3-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a hydroxy, C^-j-alkoxy, amino, C^-alkylamino or di- (C1.3-alkyl) -amino group, and R4 denotes an R7-(n-C1_3-alkyl)-phenyl group, wherein R7 denotes an amino, C^-alkylamino, di-(C-^-alkyl) -amino, co - hydroxy- C2.3 - alkyl - amino, N- (C^-alkyl) -(0-hydroxy-C2_3-alkyl-amino, di- (co-hydroxy-C2_3-alkyl) -amino or di- (co- (C^-alkoxy) -C2_3-alkyl) -amino group, or a phenyl group substituted by the group of formula -N(R12)-CO-(CH2)p-Ri3 (IV), wherein R12, p and R13 are as hereinbefore defined, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof.

A second subgroup of particularly preferred compounds of general formula I deserving special mention comprises those wherein X, Rir R3 and R5 are as hereinbefore defined, R2 denotes an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2 position of the ethyl group by a hydroxy or C^-alkoxy group or, if R4 does not denote an aminosulphonyl-phenyl or N- (C^g-alkyl) -C1_3-alkylaminocarbonyl-phenyl group, R2 may also denote a di - (C^-alkyl)-aminocarbonyl group and R4 denotes a R7- (n-C^-j-alkyl) -phenyl group, wherein R7 denotes an amino, C^g-alkylamino, di- (C1.4-alkyl) -amino, co-hydroxy-C2_3-alkyl-amino, N- (C^-j-alkyl) -oo-hydroxy--C2.3-alkyl-amino, di-(co-hydroxy-C2.3-alkyl)-amino or di- (©- (C^-alkoxy) -C2_3-alkyl) -amino group, or a phenyl group substituted by the group of formula -N(R12)-CO-(CH2)p-Ri3 (IV), wherein R12, p and R13 are as hereinbefore defined, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof.

Most particularly preferred compounds of general formula I are those wherein X denotes an oxygen atom, Rx and R5 each denote a hydrogen atom, Rz denotes a methoxycarbonyl, ethoxycarbonyl or aminocarbonyl group, R3 denotes a phenyl group and R4 denotes a phenyl group monosubstituted by the group Rs, wherein R6 denotes an N-methyl-imidazol-2-yl group, an unbranched C^-alkyl group which is terminally substituted by a C-^-alkylamino, di-(C^-alkyl) -amino, piperidino or 2,6-dimethyl-piperidino group, a group of formula -N(R12)-CO-(CH2)p-Ri3 (IV), wherein R12 denotes a Cj^-alkyl group, p denotes one of the numbers 1 or 2 and R13 denotes a di - (C^-alkyl) -amino group, or a group of formula -N(R14)-(CH2)q-(CO)r-R15 (V), wherein R14 denotes a C^-alkyl-carbonyl or C1_3-alkylsulphonyl group, q denotes one of the numbers 1, 2 or 3, r denotes the number 1 or, if q is one of the numbers 2 or 3, r may also denote the number 0 and R1S denotes a di - (C1_3-alkyl) -amino group, wherein the saturated alkyl moieties contained in the abovementioned groups which contain more than 2 carbon atoms may be straight-chain or branched, unless otherwise stated, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof.

A subgroup of most particularly preferred compounds of general formula I deserving special mention comprises those wherein X, Rx, R3 and R5 are as hereinbefore defined, R2 denotes a methoxycarbonyl or ethoxycarbonyl group and R4 denotes a di-(C^-alkyl) -amino-C^-alkylphenyl group or a phenyl group substituted by the group of formula -N(R12)-CO-(CH2)p-Ri3 (IV), wherein R12, p and R13 are as hereinbefore defined, the tautomers, the diastereomers, the enantiomers, the mixtures thereof and the salts thereof.

The following are mentioned as examples of particularly preferred compounds: (a) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone, (b) 3-Z-t(1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]- 6-carbamoyl-2 -indolinone, (c) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone, i (d) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone, (e) 3-Z-[1-(4-((2,6-dimethyl-piperidin-l-yl)-methyl)-anilino) 1-phenyl-methylene]-6 -ethoxycarbonyl-2 -indolinone, (f) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-anilino) -1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone, (g) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-ani lino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone, (h) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone, (i) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone, (j) 3-Z-[i-(4-(N-acetyl-N-dimethylaminocarbonylmethyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone, (k) 3-Z-[1-(4-ethylaminomethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone, (1) 3-Z-[1-(4-(1-methyl-imidazol-2-yl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone, (m) 3—Z—[ 1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (n) 3—Z —[ 1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (o) 3-Z-[ 1-(4-(N-(3-dimethylamino-propyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (p) 3—Z —[ 1-(4-(N-dimethylaminocarbonylmethyl-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (q) 3—Z —[ 1-(4-(N-((2-dimethylamino-ethyl)-carbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (r) 3—Z —[ 1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone and (s) 3-Z-[ 1-(4-methylaminomethyl-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (t) 3—Z —[ 1-(4-(N-((4-methyl-piperazin-l-yl)-methylcarbonyl)-N-methyl-amino)aniline)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, the tautomers, the mixtures and the salts thereof.

Another subgroup of compounds of general formula I comprises those wherein X denotes an oxygen or sulphur atom, Ri denotes a hydrogen atom or a prodrug group such as a Ci-4-alkoxycarbonyl or C2-4~alkanoyl group, intpl' ff.tdal property dffice of n.z. 2 1 DEC 20M Bpr.pivr.0 R2 denotes a carboxy group, a straight-chain or branched C^g-alkoxycarbonyl group, a C5_7-cycloalkoxycarbonyl or phenyl-C^j-alkoxycarbonyl group, an aminocarbonyl or C^-alkylaminocarbonyl group or, if R4 does not denote an aminosulphonyl-phenyl or N- (C^-alkyl) -C1.3-alkylaminocarbonyl-phenyl group, a di-(C^-alkyl)-aminocarbonyl group, R3 denotes a hydrogen atom, a C^.g-alkyl, C3_7-cycloalkyl, trifluoromethyl or heteroaryl group, a phenyl or naphthyl group, a phenyl or naphthyl group mono-or disubstituted by a fluorine, chlorine, bromine or iodine atom, by a trif luoromethyl, C^-j-alkyl or C^-alkoxy group, whilst in the event of disubstitution the substituents may be identical or different and wherein the abovementioned unsubstituted as well as the mono- and disubstituted phenyl and naphthyl groups may additionally be substituted by a hydroxy, hydroxy-Cx_3-alkyl or C1_3-alkoxy-C1.3-alkyl group, by a cyano, carboxy, carboxy-Cx_3-alkyl, C^j-alkoxycarbonyl, aminocarbonyl, C^-alkylamino-carbonyl or di- (Cjl.3-alkyl) -aminocarbonyl group, by a nitro group, by an amino, C^-alkylamino, di-(C^-alkyl)-amino or amino-Cj.-j-alkyl group, by a C^-alkylcarbonylamino, N- (C^-alkyl) -C^-alkyl-carbonylamino, C1_3 - alkyl carbonyl amino - Cx.3 - alkyl, N- (C^-alkyl) -C^-j-alkylcarbonylamino-C^-j-alkyl, C^-alkyl-sulphonylamino, C^-j-alkylsulphonylamino-C^-alkyl, N- (C^-alkyl) -C^-alkylsulphonylamino-C^-alkyl or aryl - Cx_3 - alkyl sulphonylamino group, by a cycloalkylamino, cycloalkyleneimino, cycloalkyleneiminocarbonyl , cycloalkyleneimino-C1_3-alkyl, cycloalkyleneiminocarbonyl-C^-alkyl or cycloalkyleneiminosulphonyl-C^-alkyl group having 4 to 7 ring members in each case, whilst in each case the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH or -N(C1.3-alkyl) group, or by a heteroaryl or heteroaryl-C^-alkyl group, R4 denotes a C3_7-cycloalkyl group, whilst the methylene group in the 4 position of a 6- or 7-membered cycloalkyl group may be substituted by an amino, C^-alkylamino or di- (C^-alkyl)-amino group or replaced by an -NH or -N (C^-alkyl) group, or a phenyl group substituted by the group R6, which may additionally be substituted by a fluorine, chlorine, bromine or iodine atom, by a C^-alkyl, trifluoromethyl, C^-alkoxy, carboxy, C^-alkoxycarbonyl, aminosulphonyl, nitro or cyano group, wherein R6 denotes a hydrogen, fluorine, chlorine, bromine or iodine atom, a cyano, nitro, C1.5-alkyl, C3.7-cycloalkyl, trif luoromethyl, phenyl, tetrazolyl or heteroaryl group, a C^-alkoxy group optionally sunstituted by 1 to 3 fluorine atoms, a C1.3-alkoxy-C1.3-alkoxy, phenyl-C1_3-alkoxy, amino - C2_3 - alkoxy, -alkylamino - C2.3 - alkoxy, di- (C-L.-j-alkyl) -amino-C2_3-alkoxy, phenyl-C1.3-alkylamino- C2_3-alkoxy, N- (C1_3-alkyl) -phenyl-C1_3-alkylamino-C2.3-alkoxy, C5_7-cycloalkyleneimino-C2_3-alkoxy or C-^-alkylmercapto group, a carboxy, C^-alkoxycarbonyl, aminocarbonyl, ^.3 - alkylamino-carbonyl, N- (C^-alkyl) -C1_3-alkylaminocarbonyl, phenyl--alkylamino-carbonyl, N- (C^-alkyl) -phenyl-C1_3-alkylamino-carbonyl, piperazinocarbonyl or N- (C1_3-alkyl) -piperazinocarbonyl group, I a Cj^-alkylaminocarbonyl or N- (C^-alkyl) -C^-j-alkylaminocarbonyl group wherein an alkyl moiety is substituted by a carboxy or C^-alkoxycarbonyl group or is substituted in the 2 or 3 position by a di- (C1.3-alkyl) -amino, piperazino, N-(C1.3-alkyl)-piperazino or a 4- to 7-membered cycloalkyleneimino group, a 4- to 7-membered cycloalkyleneimino group, wherein a methylene group linked to the imino group may be replaced by a carbonyl or sulphonyl group or the cycloalkylene moiety may be fused to a phenyl ring or one or two hydrogen atoms may each be replaced by a Cx„3 — alkyl group and/or in each case the methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be substituted by a carboxy, C^-alkoxycarbonyl, aminocarbonyl, Ci.3 — alkylaminocarbonyl, di - (Cx.3 - alkyl) - aminocarbonyl, phenyl-C^-alkylamino or N- (C^-j-alkyl) - phenyl-C^-alkylamino group or may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N(C^-j-alkyl) , -N(phenyl), -N(Ci.a-alkyl-carbonyl) or -N(benzoyl) group, C1.4-alkyl group which may be substituted by a hydroxy or C^-alkoxy group, by an amino, C^-alkylamino, di- (C^-alkyl) -amino, di-N- (C^-alkyl) -amino-C2_3-alkylamino, tri-N,N,N' - (C^-alkyl) -amino-C2.3-alkylamino, phenylamino, N-phenyl-C^j- alkyl -amino, phenyl -C^- alkylamino, N- (C^-alkyl) -phenyl-C1_3-alkylamino or di-(phenyl-C^-j-alkyl) -amino group, by a C1_3-alkylcarbonylamino, N-(C^-alkyl)- C^-alkyl carbonyl amino, C^-alkoxycarbonyl -C^- alkyl amino or N- (C^-alkyl) -C^-alkoxycarbonyl-C^-alkylamino group, by a C4_7-cycloalkylamino, C4_7-cycloalkyl-C1_3-alkylamino or C4_7-cycloalkenylamino group wherein position 1 of the ring is not involved in the double bond and wherein the abovementioned groups may each additionally be substituted at the amino-nitrogen atom by a C^-alkyl group wherein some or all of the hydrogen atoms are replaced by fluorine atoms, by a C5_7-cycloalkyl, C2_4-alkenyl or C1_4-alkyl group, by a 4- to 7-membered cycloalkyleneimino group, wherein a methylene group linked to the imino group may be replaced by a carbonyl or sulphonyl group or the cycloalkylene moiety may be fused to a phenyl group or to an oxazolo, imidazolo, thiazolo, pyridino, pyrazino or pyrimidino group optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, Ci.3-alkyl, -alkoxy or amino group or one or two hydrogen atoms may each be replaced by a C^-alkyl, C5_7-cycloalkyl or phenyl group and/or in each case the methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be substituted by a hydroxy, carboxy, C^-alkoxycarbonyl, aminocarbonyl, C1_3-alkylaminocarbonyl, di-(Cx_3-alkyl) -aminocarbonyl, phenyl-C1_3-alkylamino or N- (C^.j-alkyD'-phenyl-C^j-alkylamino group or may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N(C1_3-alkyl) , -N(phenyl), -N(C^-alkyl-carbonyl) or -N(benzoyl) group, by a carboxy, C^-alkoxycarbonyl, aminocarbonyl, C^-alkylaminocarbonyl or di-(C^-alkyl) -aminocarbonyl group or by a 4- to 7-membered cycloalkyleneiminocarbonyl group, an amino, pyrrolidino, piperidino, morpholino, benzoylamino or N- (C^-alkyl)-benzoylamino group, an N- (C^-alkyl) -C2_4-alkanoylamino group which is additionally substituted in the alkyl moiety by a carboxy or C1_3-alkoxycarbonyl group, a group of formula -N(R8)-CO-(CH2)n-R9 (II), wherein R8 denotes a hydrogen atom or a C1_3-alkyl group, n denotes one of the numbers 0, 1, 2 or 3 and R9 denotes an amino, C1.4-alkylamino, phenylamino, N- (C1.4-alkyl) -phenylamino, benzylamino, N- (C^-alkyl)-benzylamino or di-(C^-alkyl)-amino group, a 4- to 7-membered cycloalkyleneimino group, whilst in each case the methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (C1_3-alkyl) , - According to the invention the new compounds are obtained, for example, by the following methods known in principle from the literature: a. reacting a compound of general formula wherein X and R3 are as hereinbefore defined, R21 has the meanings given for R2 hereinbefore, Ris denotes a hydrogen atom or a protecting group for the nitrogen atom of the lactam group, wherein one of the groups R2' and Ris may also denote a bond to a solid phase optionally formed via a spacer and the other one of the groups R21 and R18 (VII) intellectual property office of n.z. 21 DEC 2004 RECEIVED (followed by page 49) be fused to the abovementioned monocyclic heterocyclic groups via two adjacent carbon atoms, the saturated alkyl and alkoxy moieties present in the groups defined above which contain more than 2 carbon atoms also include the branched isomers thereof such as, for example, the isopropyl, tert.butyl or isobutyl group, unless otherwise stated, and additionally any carboxy, amino or imino group present may be substituted by a hydroxy group, an acyl group such as the benzoyl or pyridinoyl group or a Ci-i6-alkanoyl group such as the formyl, acetyl, propionyl, butanoyl, pentanoyl or hexanoyl group, an allyloxycarbonyl group, a Ci-i6-alkoxycarbonyl group such as the methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert.butoxycarbonyl, pentoxycarbonyl, hexyloxycarbonyl, octyloxycarbonyl, nonyloxycarbonyl, decyloxycarbonyl, undecyloxycarbonyl, dodecyloxycarbonyl or hexadecyloxycarbonyl group, a phenyl-Ci-6-alkoxycarbonyl group such as the benzyloxycarbonyl, phenylethoxycarbonyl or phenylpropoxycarbonyl group, a Ci_3-alkylsulphonyl-C2-4~alkoxycarbonyl, Ci_3-alkoxy-C2-4-alkoxy-C2-4-alkoxycarbonyl or ReC0-0-(RfCRg)-0-CO group wherein Re denotes a Ci_8-alkyl, C5-7-cycloalkyl, phenyl or phenyl-Ci-3-alkyl group, Rf denotes a hydrogen atom, a Ci-3-alkyl, C5-7-cycloalkyl or phenyl group and Rg denotes a hydrogen atom, a Ci_3-alkyl or ReC0-0- (RfCRh) -0 group wherein Re and Rf are as hereinbefore defined and Rh is a hydrogen atom or a C1-3 alkyl group, INTELLECTUAL PF'VERT* OFftCi j 7 ■ 1 MAR 2005 RECElvPn (followed by page 48a) has the abovementioned meanings, and Z1 denotes a halogen atom, a hydroxy, alkoxy or aryl-alkoxy group, e.g. a chlorine or bromine atom, a methoxy, ethoxy or benzyloxy group, with an amine of general formula wherein R4 and R5 are as hereinbefore defined, and if necessary subsequently cleaving any protecting group used for the nitrogen atom of the lactam group or cleaving from a solid phase.

The protecting group for the nitrogen atom of the lactam group may be, for example, an acetyl, benzoyl, ethoxycarbonyl, tert.butyloxycarbonyl or benzyloxycarbonyl group and the solid phase may be a resin such as a 4-(21,4'-dimethoxyphenylaminomethyl)-phenoxy resin, the bond preferably being formed via the amino group, or a p-benzyloxybenzyl alcohol resin, wherein the bond is conveniently formed via an intermediate member such as a 2,5-dimethoxy-4-hydroxy-benzyl derivative.

The reaction is conveniently carried out in a solvent such as dimethylformamide, toluene, acetonitrile, tetrahydrofuran, dimethylsulphoxide, methylene chloride or mixtures thereof, optionally in the presence of an inert base such as triethylamine, N-ethyl-diisopropylamine or sodium hydrogen carbonate at temperatures between 20 and 175°C, whilst any protecting group used can be cleaved at the same time by transamidation.

H «r (VIII), If Zx in a compound of general formula VII denotes a halogen atom, the reaction is preferably carried out in the presence of an inert base at temperatures of between 20 and 120°C.

If Z1 in a compound of general formula VII denotes a hydroxy, alkoxy or arylalkoxy group, the reaction is preferably carried out at temperatures between 20 and 200°C.

If a protecting group used subsequently has to be cleaved, this is conveniently done either hydrolytically in an aqueous or alcoholic solvent, e.g. in methanol/water, ethanol/water, isopropanol/water, tetrahydrofuran/water, dioxan/water, dimethylformamide/water, methanol or ethanol in the presence of an alkali metal base such as lithium hydroxide, sodium hydroxide or potassium hydroxide at temperatures between 0 and 100°C, preferably at temperatures between 10 and 50°C, or advantageously by transamidation with an organic base such as ammonia, butylamine, dimethylamine or piperidine in a solvent such as methanol, ethanol, dimethylformamide and the mixtures thereof or in an excess of the amine used, at temperatures between 0 and 100°C, preferably at temperatures between 10 and 50°C.

Cleaving from any solid phase used is preferably carried out using trifluoroacetic acid and water at temperatures between 0 and 35°C, preferably at ambient temperature. b. In order to prepare a compound of general formula I wherein R2 has the meanings given hereinbefore, with the exception of the carboxy group: reacting a compound of general formula HOOC R, :ix), wherein / Rx and R3 to R5 are as hereinbefore defined, or the reactive derivatives thereof, with a compound of general formula H - Rn (X) , wherein R19 denotes a C1.6-alkanol, a C4_7-cycloalkanol or an aromatic alcohol, a Ci.g-alkanol which is terminally substituted in the alkyl moiety by a phenyl, heteroaryl, carboxy, C1.3-alkoxy-carbonyl, aminocarbonyl, C^-alkylamino-carbonyl or di- (C1_3-alkyl) -aminocarbonyl group, a C2_6-alkanol which is terminally substituted in the alkyl moiety by a chlorine atom or a hydroxy, G^-alkoxy, amino, C1_3-alkylamino or di-(Cx.3-alkyl) -amino group, an amino or methylamino group, an ethylamino group optionally substituted in the 2 position of the ethyl group by a hydroxy or C1_3-alkoxy group or a di-(G^-alkyl) -amino group.

The esterification or amidation is preferably carried out in a solvent such as methylene chloride, diethylether, tetrahydrofuran, toluene, dioxan, acetonitrile, dimethylsulphoxide or dimethylformamide, optionally in the presence of an inorganic or a tertiary organic base, preferably at temperatures between 20°C and the boiling temperature of the solvent used. The reaction with a corresponding acid is preferably carried out in the presence of a dehydrating agent, e.g. in the presence of isobutyl chloroformate, tetraethyl orthocarbonate, trimethyl orthoacetate, 2,2-dimethoxypropane, tetramethoxysilane, thionylchloride, trimethylchlorosilane, phosphorus trichloride, phosphorus pentoxide, N,N'-dicyclohexylcarbodiimide, N,N'-dicyclohexyl-carbodiimide/N-hydroxysuccinimide, N,N'-dicyclohexyl-carbodiimide/l-hydroxy-benzotriazole, 2-(lH-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium-tetrafluoroborate, 2-(1H-benzotriazol-l-yl)-1,1,3,3-tetramethyluronium-tetraf luoroborate/l-hydroxy-benzotriazole , N,N'-carbonyldiimidazole or triphenylphosphine/carbon tetrachloride, and optionally with the addition of a base such as pyridine, 4-dimethylaminopyridine, N-methyl-morpholine or triethylamine, conveniently at temperatures between 0 and 150°C, preferably at temperatures between 0 and 100°C, and the acylation with a corresponding reactive compound such as an anhydride, ester, imidazolide or halide thereof, is optionally carried out in the presence of a tertiary organic base such as triethylamine, N-ethyl-diisopropylamine or N-methyl-morpholine at temperatures between 0 and 150°C, preferably at temperatures between 50 and 100°C. c. In order to prepare a compound of general formula I, wherein R4 denotes a C^-alkyl group substituted by the group R7, wherein R7 denotes an amino, C^-alkylamino, di-(C^,-alkyl) -amino, phenylamino, N-phenyl-C^-j-alkyl-amino, phenyl-C^-alkylamino, N- (C1_3-alkyl) -phenyl-C1.3-alkylamino or di-(phenyl-C^-alkyl)-amino group, a co - hydroxy - C2_3 - alkyl - amino, N- (C^-alkyl) -co - hydroxy-C2_3-alkyl-amino, di- (co-hydroxy-C2_3-alkyl) -amino, di- (co- (C1.3-alkoxy) -C2_3-alkyl) -amino or N- (dioxolan-2-yl) -C1.3-alkyl-amino group, a C-L.-j-alkylcarbonylamino-C^-alkyl-amino or C^j-alkylcarbonylamino-C^-alkyl-N- (C^-alkyl) -amino group, a C^-alkylsulphonylamino, N-(C^-j-alkyl)-Cx.3 - alkyl sulphonyl amino, Cx_3 — alkyl sulphonylamino - C2.3 - alkyl - amino or C^-alkyl sulphonylamino-C2_3-alkyl-N- (C1_3-alkyl) -amino group, a group of formula -N(R10)-(CH2)m-(C0)o-Rn (III), wherein R10 denotes a hydrogen atom, a C-^-j-alkyl group, a -alkylcarbonyl, arylcarbonyl, phenyl-C^-alkyl-carbonyl, C^-alkylsulphonyl, arylsulphonyl or phenyl-Ci.j-alkylsulphonyl group, m denotes one of the numbers 1, 2, 3 or 4, o denotes the number 1 and Ri:i denotes an amino, -alkylamino, di - (C^_4 — alky 1) -amino, phenylamino, N- (C^-alkyl)-phenylamino, benzylamino, N- (C^-alkyl) -benzylamino, C^-alkoxy or C1.3-alkoxy-C1.3-alkoxy group, a di- (C^-alkyl) -amino-C^- alkylamino group optionally substituted in the 1 position by a C^-alkyl group, or a 4- to 7-membered cycloalkyleneimino group, wherein the cycloalkylene moiety may be fused to a phenyl ring or in each case the methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (C1.3-alkyl) , -N(phenyl), -N (C^-alkyl -carbonyl) or -N(benzoyl) group, a C4_7-cycloalkylamino, C^-cycloalkyl-Cj^-alkylamino or C4_7-cycloalkenylamino group wherein position 1 of the ring is not involved in the double bond and wherein the abovementioned groups may each additionally be substituted at the amino-nitrogen atom by a C5.7-cycloalkyl, C2_4-alkenyl or C^-alkyl group, or a 4- to 7-membered cycloalkyleneimino group, wherein the cycloalkylene moiety may be fused to a phenyl group or to an oxazolo, imidazolo, thiazolo, pyridino, pyrazino or pyrimidino group optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, C^j-alkyl, C1_3-alkoxy or amino group, and/or one or two hydrogen atoms may each be replaced by a Cx.3-alkyl, C5.7-cycloalkyl or phenyl group and/or the methylene group in the 3 position of a 5-membered cycloalkyleneimino group may be substituted by a hydroxy, hydroxy--alkyl, C^-alkoxy or C1.3-alkoxy-C1_3-alkyl group, in each case the methylene group in the 3 or 4 position of a 6- or 7-membered cycloalkyleneimino group may be substituted by a hydroxy, hydroxy-C^-alkyl, C^-alkoxy, C1_3-alkoxy-C1_3-alkyl, C-^-alkoxycarbonyl, aminocarbonyl, C^-alkylaminocarbonyl, di-(C1.3-alkyl) -aminocarbonyl, phenyl-C1_3-alkylamino or N-(C^-alkyl)-phenyl -Cx.3-alkylamino group or may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (C1_3-alkyl -) , -N(phenyl), -N (phenyl-C-^-alkyl-) , -N (C^-alkyl-carbonyl- ) , -N (C1.4-alkoxy-carbonyl-) , -N(benzoyl-) or -N(phenyl-C^-alkyl-carbonyl-) group, wherein a methylene group linked to an imino-nitrogen atom of the cycloalkyleneimino group may be replaced by a carbonyl or sulphonyl group or in a 5-to 7-membered monocyclic cycloalkyleneimino group or a cycloalkyleneimino group fused to a phenyl group the two methylene groups linked to the imino-nitrogen atom may each be replaced by a carbonyl group: wherein R3, R5 and X are as hereinbefore defined, R2' has the meanings given for R2 hereinbefore, R18 denotes a hydrogen atom or a protecting group for the nitrogen atom of the lactam group, wherein one of the groups R21 and R18 may also denote a bond to a solid phase optionally reacting a compound of general formula (XI) , formed via a spacer and the other one of the groups R2' and R18 has the abovementioned meanings, A denotes a C^-alkyl group and Z2 denotes a leaving group, for example an alkyl or arylsulphonyloxy group such as the methylsulphonyloxy, ethylsulphonyloxy, p-toluenesulphonyloxy or trifluoromethanesulphonyloxy group, with an amine of general formula / H—R7, (XII) , wherein R7, has the meanings given for R7 hereinbefore, and subsequently, if necessary, cleaving any protecting group used for the nitrogen atom of the lactam group, or cleaving from a solid phase.

The reaction is conveniently carried out in a solvent such as methylene chloride, tetrahydrofuran, 1,4-dioxan, toluene, acetonitrile, dimethylsulphoxide, dimethylformamide, dimethyl-acetamide, N-methylpyrrolidone or the mixtures thereof, optionally with the addition of water as a co-solvent and/or with the addition of an inert auxiliary base, e.g. sodium hydrogen carbonate, pyridine, 2,4,6-trimethylpyridine, quinoline, triethylamine, N-ethyldiisopropylamine, N-ethyl-dicyclohexylamine, 1,4-diazabicyclo[2,2,2]octane or 1,8-diazabicyclo[5,4,0]undec-7-ene, at temperatures between -50°C and +100°C, preferably between -10°C and +50°C, while any protecting group used may be cleaved at the same time by transamidat ion.

If any protecting group used for the nitrogen atom of the lactam group has to be removed or if the compound has to be cleaved from a solid phase this is carried out as described under method (a) above.

If according to the invention a compound of general formula I is obtained which contains an alkoxycarbonyl group, this may be converted by hydrolysis into a corresponding carboxy compound, or if a compound of general formula I is obtained which contains an amino or alkylamino group, this may be converted by reductive alkylation into a corresponding alkylamino or dialkylamino compound, or if a compound of general formula I is obtained which contains an amino or alkylamino group, this may be converted by acylation or sulphonation into a corresponding acyl or sulphonyl compound, or if a compound of general formula I is obtained which contains a carboxy group, this may be converted by esterification or amidation into a corresponding ester or aminocarbonyl compound, or if a compound of general formula I is obtained which contains a cycloalkyleneimino group wherein a methylene group is replaced by a sulphur atom, this may be converted by oxidation into a corresponding sulphinyl or sulphonyl compound, or if a compound of general formula I is obtained which contains a nitro group, this may be converted by reduction into a corresponding amino compound, or if a compound of general formula I is obtained wherein R4 denotes a phenyl group substituted by an amino, alkylamino, aminoalkyl or N-alkyl-amino group, this may subsequently be converted, by reaction with a corresponding cyanate, iso-cyanate or carbamoyl halide, into a corresponding urea compound of general formula I, or if a compound of general formula I is obtained wherein R4 denotes a phenyl group substituted by an amino, alkylamino, aminoalkyl or N-alkyl-amino group, this may subsequently be converted, by reaction with a corresponding compound which transfers the amidino group or by reaction with a corresponding nitrile, into a corresponding guanidino compound of general formula I.

The subsequent hydrolysis is preferably carried out in an aqueous solvent, e.g. in water, methanol/water, ethanol/water, isopropanol/water, tetrahydrofuran/water or dioxan/water, in the presence of an acid such as trifluoroacetic acid, hydrochloric acid or sulphuric acid or in the presence of an alkali metal base such as lithium hydroxide, sodium hydroxide or potassium hydroxide at temperatures between 0 and 100°C, preferably at temperatures between 10 and 50°C.

The subsequent reductive alkylation is preferably carried out in a suitable solvent such as methanol, methanol/water, methanol/water/ammonia, ethanol, ether, tetrahydrofuran, dioxan or dimethylformamide, optionally with the addition of an acid such as hydrochloric acid in the presence of catalytically activated hydrogen, e.g. hydrogen in the presence of Raney nickel, platinum or palladium/charcoal, or in the presence of a metal hydride such as sodium borohydride, lithium borohydride, sodium cyanoborohydride or lithium aluminium hydride at temperatures between 0 and 100°C, preferably at temperatures between 20 and 80°C.

The subsequent acylation or sulphonylation is preferably carried out with the corresponding free acid or a corresponding reactive compound such as the anhydride, ester, imidazolide or halide thereof, preferably in a solvent such as methylene chloride, diethylether, tetrahydrofuran, toluene, dioxan, acetonitrile, dimethylsulphoxide or dimethylformamide, optionally in the presence of an inorganic or tertiary organic base at temperatures between -20 and 200°C, preferably at temperatures between 20°C and boiling temperature of the solvent used. The reaction with the free acid may optionally be carried out in the presence of an acid-activating agent or a dehydrating agent, e.g. in the presence of isobutyl chloroformate, tetraethyl orthocarbonate, trimethyl orthoacetate, 2,2-dimethoxypropane, tetramethoxysilane, thionyl chloride, trimethylchlorosilane, phosphorus trichloride, phosphorus pentoxide, N,N'-dicyclohexyl-carbodiimide, N,N1-dicyclohexylcarbodiimide/N-hydroxysuccinimide, N,N'-dicyclohexylcarbodiimide/l-hydroxy-benzotriazole, 2 -{lH-benzotriazol-1-yl)-1,1,3,3 -tetramethyluronium-tetraf luoroborate, 2-(lH-benzotriazol-l-yl)-1,1,3,3-tetramethyluronium-tetrafluoroborate/1-hydroxy-benzotriazole, N,N1-carbonyldiimidazole or triphenylphosphine/carbon tetrachloride, and optionally with the addition of a base such as pyridine, 4-dimethylamino-pyridine, N-methyl-morpholine or triethylamine, conveniently at temperatures between 0 and 150°C, preferably at temperatures between 0 and 100°C. The reaction with a corresponding reactive compound may optionally be carried out in the presence of a tertiary organic base such as triethylamine, N-ethyl-diisopropylamine, N-methyl-morpholine or pyridine or by using an anhydride in the presence of the corresponding acid at temperatures between 0 and 150°C, preferably at temperatures between 50 and 100°C.

The subsequent esterification or amidation is conveniently carried out by reacting a corresponding reactive carboxylic acid derivative with a corresponding alcohol or amine as described hereinbefore.

The subsequent oxidation of the sulphur atom is preferably carried out in a solvent or mixture of solvents, e.g. in water, water/pyridine, acetone, methylene chloride, acetic acid, acetic acid/acetic anhydride, dilute sulphuric acid or trifluoroacetic acid, usefully at temperatures of between -80 and 100°C depending on the oxidising agent used.

In order to prepare a corresponding sulphinyl compound of general formula I the oxidation is expediently carried out with one equivalent of the oxidising agent used, e.g. with hydrogen peroxide in glacial acetic acid, trifluoroacetic acid or formic acid at 0,'to 20°C or in acetone at 0 to 60°C, with a peracid such as performic acid in glacial acetic acid or trifluoroacetic acid at 0 to 50°C or with m-chloroperbenzoic acid in methylene chloride, chloroform or dioxan at -2 0 to 80°C, with sodium metaperiodate in aqueous methanol or ethanol at -15 to 25°C, with bromine in glacial acetic acid or aqueous acetic acid optionally in the presence of a weak base such as sodium acetate, with N-bromosuccinimide in ethanol, with tert.butyl hypochlorite in methanol at -80 to -30°C, with iodobenzodichloride in aqueous pyridine at 0 to 50°C, with nitric acid in glacial acetic acid at 0 to 20°C, with chromic acid in glacial acetic acid or in acetone at 0 to 20°C and with sulphuryl chloride in methylene chloride at -70°C, the resulting thioether-chlorine complex is expediently hydrolysed with aqueous ethanol.

In order to prepare a sulphonyl compound of general formula I the oxidation is expediently carried out starting from a corresponding sulphinyl compound with one or more equivalents of the oxidising agent used or starting from a corresponding mercapto compound, expediently with two or more equivalents of the oxidising agent used, e.g. with hydrogen peroxide in glacial acetic acid/acetic anhydride, trifluoroacetic acid or in formic acid at 20 to 100°C or in acetone at 0 to 60°C, with a peracid such as performic acid or m-chloroperbenzoic acid in glacial acetic acid, trifluoroacetic acid, methylene chloride or chloroform at temperatures between 0 and 60°C, with nitric acid in glacial acetic acid at 0 to 20°C, with chromic acid, sodium periodate or potassium permanganate in acetic acid, water/sulphuric acid or in acetone at 0 to 20°C.

The subsequent reduction of a nitro group is preferably carried out by hydrogenolysis, e.g. with hydrogen in the presence of a catalyst such as palladium/charcoal or Raney nickel in a solvent such as methanol, ethanol, ethyl acetate, dimethylformamide, dimethylformamide/acetone or glacial acetic acid, optionally with the addition of an acid such as hydrochloric acid or glacial acetic acid at temperatures of between 0 and 50°C, but preferably at ambient temperature, and at a hydrogen pressure of 1 to 7 bar, but preferably 3 to 5 bar.

The subsequent preparation of a corresponding urea compound of general formula I is conveniently carried out with an inorganic cyanate or a corresponding isocyanate or carbamoylchloride, preferably in a solvent such as dimethylformamide and optionally in the presence of a tertiary organic base such as triethylamine at temperatures between 0 and 50°C, preferably at ambient.

The subsequent preparation of a corresponding guanidino compound of general formula I is conveniently carried out by reacting with a compound which transfers the amidino group such as 3,5-dimethylpyrazole-l-carboxylic acid amidine, preferably in a solvent such as dimethylformamide and optionally in the presence of a tertiary organic base such as triethylamine at temperatures of between 0 and 50°C, preferably at ambient temperature.

In the reactions described hereinbefore, any reactive groups present such as carboxy, hydroxy, amino, alkylamino or imino groups may be protected during the reaction by conventional protecting groups which are cleaved again after the reaction.

For example, a protecting group for a carboxyl group may be a trimethylsilyl, methyl, ethyl, tert.butyl, benzyl or tetrahydropyranyl group and protecting groups for a hydroxy, amino, alkylamino or imino group may be an acetyl, trifluoroacetyl, benzoyl, ethoxycarbonyl, tert.butoxycarbonyl, benzyloxycarbonyl, benzyl, methoxybenzyl or 2,4-dimethoxybenzyl group and additionally, for the amino group, a phthalyl group.

Any protecting group used is optionally subsequently cleaved for example by hydrolysis in an aqueous solvent, e.g. in water, isopropanol/water, tetrahydrofuran/water or dioxan/water, in the presence of a acid such as trifluoroacetic acid, hydrochloric acid or sulphuric acid or in the presence of an alkali metal base such as lithium hydroxide, sodium hydroxide or potassium hydroxide, at temperatures between 0 and 100°C, preferably at temperatures between 10 and 50°C.

However, a benzyl, methoxybenzyl or benzyloxycarbonyl group is cleaved, for example, hydrogenolytically, e.g. with hydrogen in the presence of a catalyst such as palladium/charcoal in a solvent such as methanol, ethanol, ethyl acetate, dimethylformamide, dimethylformamide/acetone or glacial acetic acid, optionally with the addition of an acid such as hydrochloric acid or glacial acetic acid at temperatures between 0 and 50°C, but preferably at ambient temperature, and at a hydrogen pressure of 1 to 7 bar, but preferably 3 to 5 bar.

A methoxybenzyl group may also be cleaved in the presence of an oxidising agent such as cerium(IV)ammonium nitrate in a solvent such as methylene chloride, acetonitrile or acetonitrile/water at temperatures of between 0 and 50°C, but preferably at ambient temperature.

A 2,4-dimethoxybenzyl group, however, is preferably cleaved in trifluoroacetic acid in the presence of anisole.

A tert.butyl or tert.butyloxycarbonyl group is preferably cleaved by treating with an acid such as trifluoroacetic acid or hydrochloric acijl, optionally using a solvent such as methylene chloride, dioxan, ethyl acetate or ether.

A phthalyl group is preferably cleaved in the presence of hydrazine or a primary amine such as methylamine, ethylamine or n-butylamine in a solvent such as methanol, ethanol, isopropanol, toluene/water or dioxan at temperatures between 20 and 50°C.

Moreover, chiral compounds of general formula I obtained may be resolved into their enantiomers and/or diastereomers.

Thus, for example, the compounds of general formula I obtained which occur as racemates may be separated by methods known per se (cf. Allinger N. L. and Eliel E. L. in "Topics in Stereochemistry", Vol. 6, Wiley Interscience, 1971) into their optical antipodes and compounds of general formula I with at least 2 asymmetric carbon atoms may be resolved into their diastereomers on the basis of their physical-chemical differences using methods known per se, e.g. by chromatography and/or fractional crystallisation, and, if these compounds are obtained in racemic form, they may subsequently be resolved into the enantiomers as mentioned above.

The enantiomers are preferably separated by column separation on chiral phases or by recrystallisation from an optically active solvent or by reacting with an optically active substance which forms salts or derivatives such as e.g. esters or amides with the racemic compound, particularly acids and the activated derivatives or alcohols thereof, and separating the mixture of diastereomeric salts or derivatives thus obtained, e.g. on the basis of their differences in solubility, whilst the free antipodes may be released from the pure diastereomeric salts or derivatives by the action of suitable agents. Optically active acids in common use are e.g. the D- and L-forms of tartaric acid or dibenzoyltartaric acid, di-o-tolyltartaric acid, malic acid, mandelic acid, camphorsulphonic acid, glutamic acid, N-acetylglutamic acid, aspartic acid, N-acetylaspartic acid or quinic acid. An optically active alcohol may be for example (+)- or (-)-menthol and an optically active acyl group in amides, for example, may be a (+)- or (-)-menthyloxycarbonyl group.

Furthermore, the compounds of formula I obtained may be converted into the salts thereof, particularly for pharmaceutical use into the physiologically acceptable salts with inorganic or organic acids. Acids which may be used for this purpose include for example hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid, maleic acid or methanesulphonic acid.

Moreover, if the new compounds of formula I thus obtained contain a carboxy group, they may subsequently, if desired, be converted into the salts thereof with inorganic or organic bases, particularly for pharmaceutical use into the physiologically acceptable salts thereof. Suitable bases for this purpose include for example sodium hydroxide, potassium hydroxide, eyelohexylamine, ethanolamine, diethanolamine and triethanolamine.

The compounds of general formulae VII to XII used as starting materials are known from the literature in some cases or may be obtained by methods known from the literature or may be obtained by the methods described hereinbefore and in the Examples. For example, the compounds of general formula VI are described in German Patent Application 198 24 922.5. Moreover, the compounds of general formula XI may be obtained from the compounds of general formula I wherein R4 denotes a C1.4-alkyl-phenyl group substituted in the alkyl moiety by a hydroxy group, for example, by reacting with alkyl- or arylsulphonyl chlorides.

As already mentioned, the new compounds of general formula I wherein Rx denotes a hydrogen atom or a prodrug group have valuable pharmacological properties, particularly inhibitory effects on various kinases, especially on receptor-tyrosine kinases such as VEGFR2, PDGFRa, PDGFR0, FGFR1, FGFR3, EGFR, HER2, IGF1R and HGFR, as well as on complexes of CDK's (Cyclin Dependent Kinases) such as CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8 and CDK9 with their specific cyclins (A, Bl, B2, C, DI, D2, D3, E, F, Gl, G2, H, I and K) and on viral cyclin, on the proliferation of cultivated human cells, particularly endothelial cells, e.g. in angiogenesis, but also on the proliferation of other cells, particularly tumour cells.

The biological properties of the new compounds were tested by the following standard procedure, as follows: Human umbilical endothelial cells (HUVEC) were cultivated in IMDM (Gibco BRL), supplemented with 10 % foetal calf serum (FBS) (Sigma) , 50 /iM of S-mercaptoethanol (Fluka) , standard antibiotics, 15 ^tg/ml of endothelial cell growth factor (ECGS, Collaborative Biomedical Products) and 100 /zg/ml of heparin (Sigma) on gelatine-coated culture dishes (0.2 % gelatine, Sigma) at 37°C, under 5 % CO2 in a water-saturated atmosphere.

In order to investigate the inhibitory activity of the compounds according to the invention the cells were starved for 16 hours, i.e. kept in culture medium without growth factors (ECGS + heparin). The cells were detached from the culture dishes using trypsin/EDTA and washed once in serum-containing medium. Then they were seeded out in amounts of 2.5 x 103 cells per well.

The proliferation of the cells was stimulated with 5 ng/ml of VEGFi65 (vascular endothelial growth factor; H. Weich, GBF Braunschweig) and 10 /xg/ml of heparin. As a control, 6 wells in each dish were not stimulated.

The compounds according to the invention were dissolved in 100% dimethylsulphoxide and added to the cultures in various dilutions in triplicate, the maximum dimethyl sulphoxide concentration being 0.3 %.

The cells were incubated for 76 hours at 37°C, then for a further 16 hours 3H-thymidine (0.1 /x Ci/well, Amersham) was added in order to determine the DNA synthesis. Then the radioactively labelled cells were immobilised on filter mats and the radioactivity incorporated was measured in a £-counter. In order to determine the inhibitory activity of the compounds according to the invention the mean value of the non-stimulated cells was subtracted from the mean value of the factor-stimulated cells (in the presence or absence of the compounds according to the invention).

The relative cell proliferation was calculated as a percentage of the control (HUVEC without inhibitor) and the concentration of active substance which inhibits the proliferation of the cells by 50 % (IC50) was determined.

The test results of the following compounds (a) to (s) of general formula I are given by way of example: (a) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone, (b) 3-Z- [ (1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl- methylene] -6-carbamoyl-2 -indolinone, / (c) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-me t hy1ene]-6-met hoxycarbonyl-2 -indolinone, (d) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene ]-6-ethoxycarbonyl-2 -indolinone, (e) 3-Z-[1-(4-((2,6-dimethyl-piperidin-l-yl)-methyl)-anilino 1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone, (f) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone, (g) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone, (h) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone, (i) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone, (j) 3-Z- [1- (4- (N-acetyl-N-dimethylaminocarbonylmethyl-amino) anilino) -1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (k) 3-Z-[1-(4-ethylaminomethyl-anilino)-1-phenyl-methylene]-methoxycarbonyl-2-indolinone, (1) 3-Z-[1-(4-(1-methyl-imidazol-2-yl)-anilino)-1-phenyl- methylene] -6-methoxycarbonyl-2 -indolinone, (m) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone, (n) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino) -anilino) -l-pjfienyl-methylene] -6-methoxycarbonyl-2-indolinone, (o) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone, (p) 3-Z-[1-(4-(N-dimethylaminocarbonylmethyl-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone, (q) 3-Z-[1-(4-(N-((2-dimethylamino-ethyl)-carbonyl)-N-methyl amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone, (r) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone and (s) 3-Z-[1-(4-methylaminomethyl-anilino)-1-phenyl-methylene] 6-methoxycarbonyl-2-indolinone.

The following Table contains the results found: Compound IC50 [Mm] (a) 0.04 (b) 0 .35 (c) 0 . 01 (d) i 0 . 02 (e) 0 . 05 (f) 0.01 (g) 0 . 003 (h) 0 . 01 (i) 0 . 03 (j) 0 . 02 (k) 0 . 03 (1) 0 .1 (m) 0.02 (n) 0.02 (o) 0 . 01 (P) 0.02 (q) 0.02 (r) 0.01 (s) 0.04 In view of their inhibitory effect on the proliferation of cells, particularly endothelial cells and tumour cells, the compounds of general formula I are suitable for treating diseases in which the proliferation of cells, particularly endothelial cells, plays a part.

Thus, for example, the proliferation of endothelial cells and the concomitant neovascularisation constitute a crucial stage in tumour progression (Folkman J. et al., Nature 339, 58-61, (1989); Hanahan D. and Folkman J., Cell 86., 353-365, (1996)). Furthermore, the proliferation of endothelial cells is also important in haemangiomas, in metastasisation, rheumatoid arthritis, psoriasis and ocular neovascularisation (Folkman J., Nature Med. 1, 27-31, (1995)). The therapeutic usefulness of inhibitors of endothelial cell proliferation was demonstrated in the animal model for example by O'Reilly et al. and Parangi et al. (O'Reilly M.S. et al. , Cell 8.8, 277-285, (1997); Parangi S. et al., Proc Natl Acad Sci USA 93, 2002-2007, (1996)).

The compounds of general formula I, their tautomers, their stereoisomers or the physiologically acceptable salts thereof are thus suitable, for example, for treating tumours (e.g. plate epithelial carcinoma, astrocytoma, Kaposi's sarcoma, glioblastoma, lung cancer, bladder cancer, carcinoma of the neck, melanoma, ovarian cancer, prostate cancer, breast cancer, small-cell lung cancer, glioma, colorectal carcinoma, urogenital cancer and gastrointestinal carcinoma as well as haematological cancers, such as multiple myeloma), psoriasis, arthritis (e.g. rheumatoid arthritis), haemangioma, angiofibroma, eye diseases (e.g. diabetic retinopathy), neovascular glaucoma, kidney diseases (e.g. glomerulonephritis), diabetic nephropathy, malignant nephrosclerosis, thrombic microangiopathic syndrome, transplant rejections and glomerulopathy, fibrotic diseases (e.g. cirrhosis of the liver), mesangial cell proliferative diseases, arteriosclerosis and damage to the nerve tissue and also for inhibiting the reocclusion of blood vessels after treatment with a balloon catheter, in vascular prosthetics or after the insertion of mechanical devices for keeping blood vessels open (e.g. stents), or other diseases in which cell proliferation or angiogenesis are involved.

By reason of their biological properties the compounds according to the invention may be used on their own or in conjunction with other pharmacologically active compounds, for example in tumour therapy, in monotherapy or in conjunction with other anti-tumour therapeutic agents, for example in combination with topoisomerase inhibitors (e.g. etoposide), mitosis inhibitors (e.g. vinblastin, taxol), compounds which interact with nucleic acids (e.g. cis-platin, cyclophosphamide, adriamycin), hormone antagonists (e.g. tamoxifen), inhibitors of metabolic processes (e.g. 5-FU etc.), cytokines (e.g. interferons), kinase inhibitors, antibodies, or in conjunction with radiotherapy, etc. These combinations may be'administered either simultaneously or sequentially.

For pharmaceutical use the compounds according to the invention are generally used for warm-blooded vertebrates, particularly humans, in doses of 0.01-100 mg/kg of body weight, preferably 0.1-20 mg/kg. For administration they are formulated with one or more conventional inert carriers and/or diluents, e.g. with corn starch, lactose, glucose, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water/ethanol, water/glycerol, water/sorbitol, water/polyethylene glycol, propylene glycol, stearyl alcohol, carboxymethylcellulose or fatty substances such as hard fat or suitable mixtures thereof in conventional galenic preparations such as plain or coated tablets, capsules, powders, injectable solutions, ampoules, suspensions, solutions, sprays or suppositories.

The Examples which follow are intended to illustrate the invention: Abbreviations used: FMOC = 9-fluorenylmethoxycarbonyl HOBt = 1-hydroxy-lH-benzotriazole TBTU = 0-benzotriazol-l-yl-N,N,N',N'-tetramethyluronium-tetraf luoroborate DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene Preparation of the starting compounds: Solid phase Example I 2.0 g of Rink resin (MBHA resin, made by Messrs Novabiochem) are left to swell in 30 ml of dimethylformamide. Then 40 ml of 3 0% piperidine in dimethylformamide are added and the mixture is shaken for 7 minutes to cleave the FMOC protecting group. The resin is then washed repeatedly with dimethylformamide. Then 0.4 g of 2-indolinone-6-carboxylic acid (prepared analogously to Langenbeck et al., Justus Liebigs Ann. Chem. 499. 201-208 (1932)), 297 mg HOBt, 706 mg TBTU and 0.9 ml of N-ethyl-diisopropylamine in 30 ml of dimethylformamide are added and the mixture is shaken for 1 hour. Then the solution is suction filtered and the resin is washed five times with 30 ml of dimethylformamide and three times with 3 0 ml of methylene chloride. To dry it, nitrogen is blown through the resin.

Yield: 1.9 g of charged resin Solid phase example II 1.9 g of the resin obtained in Example I are stirred with 6 ml of acetic anhydride and 6 ml of triethyl orthobenzoate for 3 hours at 110°C. Then the mixture is left to cool and the resin is washed with dimethylformamide and subsequently with methylene chloride.

Yield: 1.9 g of moist resin t The following charged resins are prepared analogously to Example II: (1) resin charged with 3-Z-(1-ethoxy-methylene)-6-carbamoyl-2-indolinone Prepared by reacting the resin obtained according to Example I with triethyl orthoformate (2) resin charged with 3-Z-(1-methoxy-l-methyl-methylene)-6-carbamoyl-2 -indolinone Prepared by reacting the resin obtained according to Example I with trimethyl orthoacetate (3) resin charged with 3-Z-(1-methoxy-l-ethyl-methylene)-6-carbamoyl-2 -indolinone Prepared by reacting the resin obtained according to Example I with trimethyl orthopropionate (4) resin charged with 3-Z-(1-methoxy-l-propyl-methylene)-6-carbamoyl-2 -indolinone Prepared by reacting the product of Example I and trimethyl orthobutyrate Example III N-(4-nitrophenvl)-N-methvl-methanesulphonamide 3.0 g of N-methyl-4-nitroaniline are dissolved in 20 ml of pyridine and 2.4 g of methanesulphonic acid chloride added dropwise at room temperature. The mixture is stirred for 12 hours at room temperature. After this time the mixture is poured onto water, the precipitate formed is filtered off and dried at 50°C in vacuo.

Yield: 4.0 g (87 % of theory), Rf value: 0.5 (silica gel, ethyl acetate/toluene = 7:3) Melting point: 107-108 °C Example IV N-(2-dimethvlamino-ethvl)-N-methvlsulphonvl-4-nitroaniline 38.9 g of N-methylsulphonyl-4-nitroaniline are dissolved in 2.0 1 of acetone, 51.9 g of l-chloro-2-dimethylamino-ethane, 77.4 g of potassium carbonate and 5.0 g of sodium iodide are added and the mixture is stirred for a total of 4 days at 50°C, while after 12 hours a further 25.9 g of l-chloro-2-dimethylamino-ethane, 49.8 g of potassium carbonate and 5.0 g of sodium iodide in 500 ml of acetone are added and after 3 6 hours another 26.0 g of l-chloro-2-dimethylamino-ethane, 50.0 g of potassium carbonate and 5.0 g of sodium iodide in 100 ml of acetone are added. After this time the mixture is filtered and the filtrate evaporated down. The residue is stirred with ether, suction filtered and dried at 40°C.

Yield: 25.3 g (49 % of theory), Rf value: 0.5 (silica gel, methylene chloride/methanol/ammonia = 9:1:0.1) C11H17N304S ESI mass spectrum: m/z = 288 [M+H+] The following compounds are prepared analogously to Example IV: (1) 4-[N-(3-dimethylamino-propyl)-N-methylsulphonyl-amino]-nitrobenzene (2) N-carboxymethyl-N-methylsulphonyl-4-nitroaniline (3) N-cyanomethyl-N,r methyl sulphonyl-p-phenylenediamine (4) 4-[N-(2-(N-benzyl-N-methyl-amino)-ethyl)-N-methylsulphonyl-amino]-nitrobenzene (5) 4-[N-(3-phthalimido-2-yl-propyl)-N-methylsulphonyl-amino]-nitrobenzene (6) 4-[N-(3-(N-benzyl-N-methyl-amino)-propyl)-N-methylsulphonyl-amino]-nitrobenzene Example V N-(dimethylaminocarbonyl-methyl)-N-methylsulphonyl-4- nitroaniline 7.0 g of N-carboxymethyl-N-methylsulphonyl-4-nitroaniline, 2.5 g of dimethylamine hydrochloride, 8.1 g of TBTU and 3.9 g of HOBT are dissolved in 125 ml of dimethylformamide and at 0°C 17.6 ml of N-ethyl-diisopropylamine are added. The mixture is stirred for 4 hours at room temperature, diluted with 1 1 of water and the precipitate formed is suction filtered. After washing with water, ethanol and ether the residue is dried at 70°C in vacuo.

Yield: 5.3 g (69 % of theory), Rf value: 0.40 (silica gel, methylene chloride/methanol = 9:1) C^H^OsS ESI mass spectrum: m/z = 300 [M-H"] The following compounds are prepared analogously to Example V: (1) 4-[(N-dimethylaminocarbonylmethyl)-amino]-nitrobenzene prepared from 4-(N-carboxymethyl-amino)-nitrobenzene and dimethylamine hydrochloride (2) 4-(N-methylaminocarbonylmethyl-N-methylsulphonyl-amino)-nitrobenzene Prepared from N-carboxymethyl-N-methylsulphonyl-4-nitroaniline and methylamine hydrochloride (3) 4-[(N-(methylcarbamoyl-methyl)-N-methyl-amino)-methyl]-nitrobenzene Prepared from 4-[(N-carboxymethyl-N-methyl-amino)-methyl]-nitrobenzene and methylamine hydrochloride (4) 4-[(N-(dimethylcarbamoyl-methyl)-N-methyl-amino)-methyl] -nitrobenzene Prepared from 4-[(N-carboxymethyl-N-methyl-amino)-methyl]-nitrobenzene and dimethylamine hydrochloride Example VI 4-TN-(2-dimethvlamino-ethvl)-N-acetvl-aminol -nitrobenzene 3.6 g of 4-(2-dimethylamino-ethylamino)-nitrobenzene (according to Gabbay et al., J. Am. Chem. Soc. 91, 5136 (1969)) are dissolved in 50 ml of methylene chloride and 5.0 ml of triethylamine are added. 1.3 ml of acetyl chloride are slowly added dropwise to this mixture at room temperature and the mixture is stirred for 2 hours at room temperature. After this time another 5.0 ml of triethylamine and 1.3 ml of acetylchloride are added and the mixture is refluxed for another 2 hours. The solvent is removed, the residue is taken up in ethyl acetate and the organic phase is extracted twice with water. After drying over MgS04 the solvent is removed and the residue dried in vacuo.

Yield: 2.0 g (45 % of theory), Rf value: 0.55 (silica gel, methylene chloride/methanol/ammonia = 9:1:0.1) ESI mass spectrum: m/z = 252 [M+H+] The following compounds are prepared analogously to Example VI : (1) 4-[N-(3-dimethylamino-propyl)-N-acetyl-amino]-nitrobenzene Prepared from 4-(3-dimethylamino-propylamino)-nitrobenzene (according to Gabbay et al., J. Am. Chem. Soc. 91, 5136 (1969) and acetyl chloride (2) 4-[N-(2-dimethylamino-ethyl)-N-propionyl-amino]-nitrobenzene Prepared from 4-(2-dimethylamino-ethylamino)-nitrobenzene and propionyl chloride (3) 4-[N-acetyl-N-(dimethylaminocarbonylmethyl)-amino]-nitrobenzene Prepared from 4-[N-(dimethylaminocarbonylmethyl)-amino]-nitrobenzene and acetyl chloride (4) 4-[N-(2-dimethylamino-ethyl)-N-butyryl-amino]-nitrobenzene Prepared from 4-(2-dimethylamino-ethylamino)-nitrobenzene and butyryl chloride (5) 4-[N-(2-dimethylamino-ethyl)-N-isobutyryl-amino]-nitrobenzene Prepared from 4-(2-dimethylamino-ethylamino)-nitrobenzene and isobutyryl chloride (6) 4-[N-(2-dimethylamino-ethyl)-N-benzoyl-amino]-nitrobenzene Prepared from 4-(2-dimethylamino-ethylamino)-nitrobenzene and benzoyl chloride (7) 4-[N-(2-dimethylamino-ethyl)-N-acetyl-amino]-1,3-dinitrobenzene Prepared from 4-(2-dimethylamino-ethyl-amino)-1,3-dinitrobenzene and acetyl chloride (8) 4-[N-(2-dimethylamino-ethyl)-N-(furan-2-carbonyl)-amino]-nitrobenzene Prepared from 4-(2-dimethylamino-ethylamino)-nitrobenzene and furan-2-carbonyl chloride (9) 4-[N-(2-dimethylamino-ethyl)-N-(2-methoxy-benzoyl)-amino]-nitrobenzene Prepared from 4-(2-dimethylamino-ethylamino)-nitrobenzene and 2-methoxy-benzoyl chloride (10) 4-[N-(2-dimethylamino-ethyl)-N-(pyridine-3-carbonyl)-amino]-nitrobenzene Prepared from 4-(2-dimethylamino-ethylamino)-nitrobenzene and nicotinic acid chloride (11) 4-[N-(2-dimethylamino-ethyl)-N-(phenyl-acetyl)-amino]-nitrobenzene Prepared from 4-(2-dimethylamino-ethylamino)-nitrobenzene and phenylacetyl-chloride (12) 4-[N-(2-dimethylamino-ethyl)-N-acetyl-amino]-3-bromo-nitrobenzene Prepared from 4-[N-(2-dimethylamino-ethyl)-amino]-3-bromo-nitrobenzene and acetyl chloride (13) N-acryloyl-N-methyl-4-nitro-aniline Prepared from 4-methylamino-nitrobenzene and acrylic acid chloride (14) N-acryloyl-N-isopropyl-4-nitro-aniline Prepared from 4-isopropylamino-nitrobenzene and acrylic acid chloride (15) N-acryloyl-N-benzyl-4-nitro-aniline Prepared from 4-benjkylamino-nitrobenzene and acrylic acid chloride (16) N-bromoacetyl-N-methyl-4-nitro-aniline Prepared from 4-methylamino-nitrobenzene and bromoacetyl chloride (17) N-bromoacetyl-N-isopropyl-4-nitro-aniline Prepared from 4-isopropylamino-nitrobenzene and bromoacetyl chloride (18) N-bromoacetyl-N-benzyl-4-nitro-aniline Prepared from 4-benzylamino-nitrobenzene and bromoacetyl chloride Example VII N-(dimethvlaminomethvlcarbonvl)-N-methvl-4-nitro-aniline 1.8 g of dimethylamine hydrochloride and 5.5 g of potassium carbonate are placed in 80 ml of acetone and 4.2 g of N-bromoacetyl-N-methyl-4-nitroaniline are added in three batches at room temperature. The mixture is stirred for 12 hours at room temperature. After this time the mixture is filtered and the filtrate is evaporated down. The residue is dissolved in ethyl acetate, washed twice with water, dried over sodium sulphate and finally concentrated by rotary evaporation.

Yield: 2.8 g (79 % of theory), Rf value: 0.5 (silica gel, ethyl acetate/methanol = 7:3) Melting point: 121-122°C The following compounds are prepared analogously to Example VII : (1) N-(piperidin-l-yl-methylcarbonyl)-N-methyl-4-nitroaniline (2) N-(morpholin-4-yl-methylcarbonyl)-N-methyl-4-nitroaniline (3) N-[(4-benzyl-piperazin-l-yl)-methylcarbonyl]-N-methyl-4-nitroaniline (4) N-(pyrrolidin-l-yl-methylcarbonyl)-N-methyl-4-nitroaniline (5) N-[(N-aminocarbonylmethyl-N-methyl-amino)-methylcarbonyl]-N-methyl-4-nitroaniline (6) N-[(N-benzyl-N-methyl-amino)-methylcarbonyl]-N-methyl-4-nitroaniline (7) N-[di-(2-methoxyethyl)-amino-methylcarbonyl]-N-methyl-4-nitroaniline (8) N-(dimethylaminomethylcarbonyl)-N-isopropyl-4-nitro-aniline (9) N-(piperidin-l-yl-methylcarbonyl)-N-isopropyl-4-nitro-aniline (10) N-[(4-tert.butoxycarbonyl-piperazin-l-yl)-methylcarbonyl]-N-isopropyl-4-nitro-aniline (11) N-[(N-benzyl-N-methyl-amino)-methylcarbonyl]-N-benzyl-4-nitro-aniline (12) N-(dimethylaminomethylcarbonyl)-N-benzyl-4-nitro-aniline (13) N-(piperidin-l-yl-methylcarbonyl)-N-benzyl-4-nitro aniline (14) N-[di-(2-hydroxyethyl)-amino-methylcarbonyl]-N-methyl-4-nitroaniline (15) N-[(N-(2-methoxyethyl)-N-methyl-amino)-methylcarbonyl]-N-methyl-4-nitroaniline (16) N-[(N-(2-dimethylamino-ethyl)-N-methyl-amino)-methylcarbonyl]-N-methyl-4-nitroaniline (17) N-[(4-methyl-piperazin-l-yl)-methylcarbonyl]-N-methyl-4-nitroaniline (18) N-[(imidazol-l-yl)-methylcarbonyl]-N-methyl-4-nitroaniline (19) N-[(phthalimido-2-yl)-methylcarbonyl]-N-methyl-4-nitroaniline Example VIII N-T(2-dimethvlamino-ethvl)-carbonvll -N-benzvl-4-nitro-aniline 0.5 g of dimethylamine hydrochloride, 1.1 ml of triethylamine and 1.2 g of N-acryloyl-N-benzyl-4-nitro-aniline are dissolved in 50 ml of methanol and stirred for 24 hours at room temperature. After this time the mixture is evaporated down. The residue is purified over an aluminium oxide column (activity 2-3) with methylene chloride/ethanol 50:1 as eluant. Yield: 1.4 g (98 % of theory), Rf value: 0.8 (aluminium oxide, methylene chloride/ethanol = 20:1) Melting point: 73°C The following compounds are prepared analogously to Example VIII: (1) N-[(2-dimethylamino-ethyl)-carbonyl]-N-isopropyl-4-nitroaniline Prepared from N-acryloyl-N-isopropyl-4-nitro-aniline and dimethylamine hydrochloride (2) N-t(2-dimethylamino-ethyl)-carbonyl]-N-methyl-4-nitroaniline Prepared from N-acryloyl-N-methyl-4-nitro-aniline and dimethylamine hydrochloride (3) N-[(2-(4-tert.butoxycarbonyl-piperazin-l-yl)-ethyl)-carbonyl]-N-methyl-4-nitro-aniline Prepared from N-acryloyl-N-methyl-4-nitro-aniline and N-tert.butoxycarbonyl-piperazine (4) N-[(2-(piperidin-l-yl)-ethyl)-carbonyl]-N-methyl-4-nitro-aniline Prepared from N-acryloyl-N-methyl-4-nitro-aniline and piperidine (5) N-[(2-(N-benzyl-N-methyl-amino)-ethyl)-carbonyl]-N-methyl-4-nitro-aniline Prepared from N-acryloyl-N-methyl-4-nitro-aniline and N-benzyl-N-methyl-amine Example IX 4-(4-methvl-pjperazine-l-vl)-nitrobenzene 31.5 g of 4-chloro-l-nitrobenzene and 44.4 ml of 1-methylpiperazine are combined and stirred for 18 hours at 90°C. Then the solution is poured onto ice water and the precipitate formed is suction filtered, washed with water and recrystallised from ethanol/water 1:1. The residue is dried in vacuo at 75°C.

Yield: 44.0 g (99 % of theory), Rf value: 0.5 (silica gel, methylene chloride/methanol = 10:1) Melting point: 108-112°C The following compounds are prepared analogously to Example IX: (1) N-(2-dimethylaminoethyl)-N-methyl-4-nitroaniline Prepared from 1-fluoro-4-nitrobenzene and l-dimethylamino-2-methylamino-ethane (2) N-(3-dimethylaminopropyl)-N-methyl-4-nitroaniline Prepared from 1-fluoro-4-nitrobenzene and l-dimethylamino-3-methylamino-propane (3) 4-(N-carboxymethyl-amino)-nitrobenzene Prepared from 1-fluoro-4-nitrobenzene and glycine (4) N-eyelohexyl-p-pheny1enediamine Prepared from 1-fluoro-4-nitrobenzene and cyclohexylamine (5) 6-[N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino]-3-phthalimido-2-yl-nitrobenzene Prepared from 2-nitro-4-phthalimido-2-yl-fluorobenzene, N-(2-dimethylamino-ethyl)-methanesulphonamide and sodium hydride as base (6) 6-[N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino]-1,3-dinitrobenzene Prepared from 2,4-dinitro-chlorobenzene, N-(2-dimethylamino-ethyl) -methanesulphonamide and sodium hydride as base (7) 4-[N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino]-3-chloro-nitrobenzene Prepared from 2-fluoro-5-nitro-chlorobenzene, N-(2-dimethylamino-ethyl) -methanesulphonamide and sodium hydride as base (8) 4-(2-dimethylamino-ethyl-amino)-1,3-dinitrobenzene Prepared from l-chloro-2,4-dinitro-benzene and N,N-dimethyl-ethylenediamine (9) 4-[N-(2-dimethylamino-ethyl)-N-(ethylsulphonyl)-amino]-nitrobenzene Prepared from 1-fluoro-4-nitro-benzene, N-(2-dimethylamino-ethyl) -ethanesulphonamide and sodium hydride as base (10) 4-[N-(2-dimethylamino-ethyl)-N-(propylsulphonyl)-amino]-nitrobenzene Prepared from l-fluoro-4-nitro-benzene, N-(2-dimethylamino-ethyl) -propanesulphonamide and sodium hydride as base (11) 4-[N-(2-dimethylamino-ethyl)-N-(butylsulphonyl)-amino]-nitrobenzene Prepared from l-fluoro-4-nitro-benzene, N-(2-dimethylamino-ethyl) -butanesulphonamide and sodium hydride as base (12) 4-[N-(2-dimethylamino-ethyl)-N-(benzylsulphonyl)-amino]-nitrobenzene Prepared from 1-fluoro-4-nitro-benzene, N-(2-dimethylamino-ethyl) -C-phenylmethanesulphonamide and sodium hydride as base (13) 4-[N-(2-dimethylamino-ethyl)-N-(phenylsulphonyl)-amino]-nitrobenzene Prepared from l-fluoro-4-nitro-benzene, N-(2-dimethylamino-ethyl ) -benzenesulphonamide and sodium hydride as base (14) 4-[N-(2-dimethylamino-ethyl)-N-(isopropylsulphonyl)-amino]-nitrobenzene Prepared from l-fluoro-4-nitro-benzene, N-(2-dimethylamino- ethyl)-isopropylsulphonamide and sodium hydride as base (15) 4-[N-(2-dimethylamino-ethyl)-amino]-3-bromo-nitrobenzene Prepared from 2-bromo-l-fluoro-4-nitro-benzene and N,N-dimethyl-ethylenediamine (16) 4 -isopropylamino-nitrobenzene Prepared from 1-flu6ro-4-nitrobenzene and isopropylamine (17) 4-benzylamino-nitrobenzene Prepared from 1-fluoro-4-nitrobenzene and benzylamine Example X 4-(imidazol-4-vl)-nitrobenzene 9.5 g of 2-phenylimidazole are carefully dissolved in 50 ml of concentrated sulphuric acid and 5.8 g of ammonium nitrate are added to this solution at 0°C. After a further 60 minutes stirring at 0°C the mixture is poured onto ice water, made basic with ammonia water and the precipitate formed is suction filtered and recrystallised from ethanol.

Yield: 8.0 g (64 % of theory), Rf value: 0.6 (silica gel, ethyl acetate/ethanol = 10:1) C9H7N302 Mass spectrum: m/z = 189 [M+] The following compounds are prepared analogously to Example X: (1) 4-(imidazol-2-yl)-nitrobenzene Prepared from 4-(imidazol-2-yl)-benzene (2) 4-(5-methyl-imidazol-4-yl)-nitrobenzene Prepared from 4-methyl-5-phenyl-imidazole (J. Heterocycl.

Chem. 1983, 20, 1277-1281) Example XI 4-(2-(imidazol-4-vl)-ethylene)-nitrobenzene 1.5 g of 4-nitrobenzaldehyde and 7.45 g of (N-trityl-imidazol-4-yl-methyl)-triphenylphosphonium chloride are dissolved in 75 ml of tetrahydrofuran and to this solution 3.0 ml of DBU are added dropwise at room temperature. After a further 120 minutes stirring at room temperature the mixture is poured onto water and the precipitate formed is suction filtered. The product is taken up in 25 ml of IN hydrochloric acid and refluxed for 4 hours. After this time it is neutralised with ammoniacal water, extracted with ethyl acetate and the organic phase is washed with water, dried over sodium sulphate and evaporated down. The residue is purified over a silica gel column with methylene chloride/methanol 10:1 as eluant.

Yield: 1.0 g of (47 % of theory), Rf value: 0.6 (silica gel, ethyl acetate/ethanol = 10:1) Melting point: 185-188°C Example XII 4-(pjperidin-l-vl-methvl)-nitrobenzene 40.0 g of 4-nitrobenzyl bromide are dissolved in 500 ml of methylene chloride, 51.5 ml of triethylamine are added and 18.3 ml of piperidine are carefully added dropwise. After the end of the exothermic reaction the mixture is refluxed for another 30 minutes. After cooling it is washed with water and the organic phase is dried over sodium sulphate. Finally, the organic phase is evaporated down.

Yield: 36.3 g of (89 % of theory), Rf value: 0.6 (silica gel, methylene chloride/methanol = 9:1) ^12^16^2^2 Mass spectrum: m/z = 221 [M+] The following compounds are prepared analogously to Example XII: (1) 4-[(2,6-dimethyl-piperidin-l-yl)-methyl]-nitrobenzene (2) 3-(N,N-dimethyl-aminomethyl)-nitrobenzene (3) 4-(N,N-dimethyl-aminomethyl)-nitrobenzene (4) 4-(2-dimethylamino-ethyl)-nitrobenzene (5) 4-(2-diethylamino-ethyl)-nitrobenzene (6) 4-(diethylamino-methyl)-nitrobenzene (7) 4-(N-benzyl-N-methyl-aminomethyl)-nitrobenzene (8) 4-(N-ethyl-N-methyl-aminomethyl)-nitrobenzene (9) 4-[N-(n-hexyl)-N-methyl-aminomethyl]-nitrobenzene (10) 4-(thiomorpholin-4-yl-methyl)-nitrobenzene (11) 4-[(4-methyl-piperazine-l-yl)-methyl]-nitrobenzene (12) 4-(imidazol-l-yl-methyl)-nitrobenzene (13) 4-[2-(4-hydroxy-piperidin-l-yl)-ethyl-amino]-nitrobenzene (14) 4-[(3-hydroxy-pyrrolidin-l-yl)-methyl] -nitrobenzene (15) 4-(1,2,4-triazol-l-yl-methyl)-nitrobenzene (16) 4-(1,2,3 -triazol-2-yl-methyl)-nitrobenzene (17) 4-(1,2,3-triazol-l-yl-methyl)-nitrobenzene (18) 4-[(N-ethoxycarbonylmethyl-N-methyl-amino)-methyl]- nitrobenzene (19) 4-t(N-aminocarbonylmethyl-N-methyl-amino)-methyl]-nitrobenzene (20) 4-(azetidin-l-yl-methyl)-nitrobenzene (21) 4-t(di-(2-methoxy-ethyl)-amino)-methyl]-nitrobenzene (22) 4-[N-(N-tert.butoxycarbonyl-3-amino-propyl)-N-methyl-aminomethyl]-nitrobenzene (23) 4-[(N-propyl-N-methyl-amino)-methyl]-nitrobenzene (24) 4-[(N-(2-dimethylamino-ethyl)-N-methyl-amino)-methyl]-nitrobenzene (25) 4-[(N-(3-dimethylamino-propyl)-N-methyl-amino)-methyl] nitrobenzene (26) 4-[(N-(2-methoxy-ethyl)-N-methyl-amino)-methyl]-nitrobenzene (27) 4-[(N-(2-hydroxy-ethyl)-N-methyl-amino)-methyl]-nitrobenzene (28) 4-[(N-(dioxolan-2-yl-methyl)-N-methyl-amino)-methyl]-nitrobenzene (29) 4-(3-oxo-piperazine-l-yl-methyl)-nitrobenzene Example XIII 4-T(N-carboxvmethvl-N-methvl-amino)-methyl] -nitrobenzene 7.33 g of 4-[(N-ethoxycarbonylmethyl-N-methyl-amino)-methyl]- / nitrobenzene are dissolved in 140 ml of ethanol, 34.0 ml of IN sodium hydroxide solution are added and the mixture is stirred for half an hour at room temperature. After this time the mixture is neutralised with 34 ml of IN hydrochloric acid, the solvent removed, the residue taken up in methylene chloride and extracted with water. The aqueous phase is evaporated down and the residue is recrystallised from methylene chloride.

Yield: 5.43 g (84 % of theory), Rf value: 0.4 (silica gel, methylene chloride/methanol = 2:1) C10H12N2O4 Mass spectrum: m/z = 223 [M+] Example XIV 4-(N-ethyl-aminomethyl)-nitrobenzene 6.0 g of 4-nitrobenzyl bromide are dissolved in 25 ml of ethanol, combined with 25 ml of 10% ethanolic ethylamine solution and refluxed for 2 hours. Then the solution is concentrated by rotary evaporation, the residue is taken up with methylene chloride and washed with dilute sodium hydroxide solution. Finally the organic phase is evaporated down.

Yield: 2.3 g (46 % of theory), Rf value: 0.2 (silica gel, methylene chloride/methanol = 9:1) C9H12N202 ESI mass spectrum: m/z = 179 [M-H~] The following compounds are prepared analogously to Example XIV: (1) 4-[N-(4-chlorobenzyl)-aminomethyl] -nitrobenzene (2) 4-(N-cyclohexyl-aminoraethyl)-nitrobenzene (3) 4-(N-isopropyl-aminomethyl)-nitrobenzene (4) 4-(N-propyl-aminomethyl)-nitrobenzene (5) 4-(N-methyl-aminomethyl)-nitrobenzene (6) 4-(N-butyl-aminomethyl)-nitrobenzene (7) 4-(N-methoxycarbonylmethyl-aminomethyl)-nitrobenzene (8) 4-(N-benzyl-aminomethyl)-nitrobenzene (9) 4-(aminomethyl)-nitrobenzene (10) 4-(pyrrolidin-l-yl-methyl)-nitrobenzene (11) 4-(morpholin-4-yl-methyl)-nitrobenzene (12) 4-(hexamethyleneiminomethyl)-nitrobenzene (13) 4-(4-hydroxy-piperidin-l-yl-methyl)-nitrobenzene (14) 4-(4-methoxy-piperidin-1-yl-methyl)-nitrobenzene (15) 4-(4-methyl-piperidin-l-yl-methyl)-nitrobenzene (16) 4-(4-ethyl-piperidin-l-yl-methyl)-nitrobenzene (17) 4-(4-isopropyl-piperidin-l-yl-methyl)-nitrobenzene (18) 4-(4-phenyl-piperidin-l-yl-methyl)-nitrobenzene (19) 4-(4-benzyl-piperidin-l-yl-methyl)-nitrobenzene (20) 4-(4-ethoxycarbonyl-piperidin-l-yl-methyl)-nitrobenzene (21) 4-(N,N-dipropyl-aminomethyl)-nitrobenzene (22) 4-(4-tert.butoxycarbonyl-piperazin-l-yl-methyl)-nitrobenzene (23) 4- (2-morpholin-L4-yl-ethyl) -nitrobenzene (24) 4-(2-pyrrolidin-l-yl-ethyl)-nitrobenzene (25) 4-(2-piperidin-l-yl-ethyl)-nitrobenzene (26) 4-(N-ethyl-N-benzyl-aminomethyl)-nitrobenzene (27) 4-(N-propyl-N-benzyl-aminomethyl)-nitrobenzene (28) 4-[N-methyl-N-(4-chlorobenzyl)-aminomethyl]-nitrobenzene (29) 4-[N-methyl-N-(4-bromobenzyl)-aminomethyl] -nitrobenzene (30) 4-[N-methyl-N-(4-fluorobenzyl)-aminomethyl]-nitrobenzene (31) 4-[N-methyl-N-(4-methylbenzyl)-aminomethyl]-nitrobenzene (32) 4-[N-methyl-N-(3-chlorobenzyl)-aminomethyl] -nitrobenzene (33) 4-[N-methyl-N-(3,4-dimethoxybenzyl)-aminomethyl]-nitrobenzene (34) 4-[N-methyl-N-(4-methoxybenzyl)-aminomethyl]-nitrobenzene (35) 4-(N-2,2,2-trifluoroethyl-N-benzyl-aminomethyl)-nitrobenzene (36) 4-[N-2,2,2-trifluoroethyl-N-(4-chlorobenzyl)- aminomethyl]-nitrobenzene (37) 4-(thiomorpholin-4-yl-methyl)-nitrobenzene (38) 4-(azetidion-l-yl-methyl)-nitrobenzene (39) 4-(3,4-dihydropyrrolidin-1-yl-methyl)-nitrobenzene (40) 4-(3,4-dihydropiperidin-l-yl-methyl)-nitrobenzene (41) 4-(2-methoxycarbonyl-pyrrolidin-1-yl-methyl)-nitrobenzene (42) 4-(3,5-dimethyl-piperidin-l-yl-methyl)-nitrobenzene (43) 4-(4-phenyl-piperazin-l-yl-methyl)-nitrobenzene (44) 4-(4-phenyl-4-hydroxy-piperidin-1-yl-methyl)-nitrobenzene (45) 4-[N-(3,4,5-trimethoxybenzyl-N-methyl-aminomethyl)-nitrobenzene (46) 4-[N-(3,4-dimethoxybenzyl)-N-ethyl-aminomethyl]-nitrobenzene (47) 4-[N-(2,6-dichlorobenzyl)-N-methyl)-aminomethyl]-nitrobenzene (48) 4-[N-(4-trifluoromethylbenzyl)-N-methyl)-aminomethyl]-nitrobenzene (49) 4-(N-benzyl-N-isopropyl-aminomethyl)-nitrobenzene (50) 4-(N-benzyl-N-tert.butyl-aminomethyl)-nitrobenzene (51) 4-(N,N-diisopropyl-aminomethyl)-nitrobenzene (52) 4-(N,N-diisobutyl-aminomethyl)-nitrobenzene (53) 4 -(2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl)-nitrobenzene (54) 4-(2,3-dihydro-isoindol-2-yl-methyl)-nitrobenzene (55) 4-(6,7-dimethoXy-l,2,3,4 -tetrahydro-isoquinolin-2-yl-methyl) -nitrobenzene (56) 4-(1, 2, 3,4-tetrahydro-isoquinolin-2-yl-methyl)-nitrobenzene (57) 4-[N-(2-hydroxyethyl)-N-benzyl-aminomethyl] -nitrobenzene (58) 4-[N-(1-ethyl-pentyl)-N-(pyridin-2-yl-methyl)-aminomethyl]-nitrobenzene (59) 4-(piperin-1-yl-methyl)-1,3-dinitrobenzene (60) 4-(N-phenethyl-N-methyl-aminomethyl)-nitrobenzene (61) 4-[N-(3,4-dihydroxy-phenethyl)-N-methyl-aminomethyl]-nitrobenzene (62) 4-[N-(3,4,5-trimethoxy-phenethyl)-N-methyl-aminomethyl]-nitrobenzene (63) 4-[N-(3,4-dimethoxy-phenethyl)-N-methyl-aminomethyl]-nitrobenzene (64) 4-[N-(3,4-dimethoxy-benzyl)-N-methyl-aminomethyl]-nitrobenzene (65) 4-[N-(4-chloro-benzyl)-N-methyl-aminomethyl]-nitrobenzene (66) 4-[N-(4-bromo-benzyl)-N-methyl-aminomethyl]-nitrobenzene (67) 4-[N-(4-fluoro-benzyl)-N-methyl-aminomethyl]-nitrobenzene (68) 4-[N-(4-methyl-benzyl)-N-methyl-aminomethyl]-nitrobenzene (69) 4-[N-(4-nitro-phenethyl)-N-methyl-aminomethyl]-nitrobenzene (70) 4-(N-phenethyl-N-benzyl-aminomethyl)-nitrobenzene (71) 4-(N-phenethyl-N-cyclohexyl-aminomethyl)-nitrobenzene (72) 4-[N-(2-(pyridin-2-yl)-ethyl)-N-methyl-aminomethyl]-nitrobenzene (73) 4-[N-(2-(pyridin-4-yl)-ethyl)-N-methyl-aminomethyl]-nitrobenzene (74) 4-[N-(pyridin-4-yl-methyl)-N-methyl-aminomethyl]-nitrobenzene (75) 4-(N,N-dibenzyl-aminomethyl)-nitrobenzene (76) 4-[N-(4-nitro-phenethyl)-N-propyl-aminomethyl]-nitrobenzene (77) 4-(N-benzyl-N-(3-cyano-propyl)-aminomethyl)-nitrobenzene (78) 4-(N-benzyl-N-allyl-aminomethyl)-nitrobenzene (79) 4-[N-benzyl-N-(2,2,2-trifluoroethyl)-aminomethyl]-nitrobenzene (80) 4-[N-(2-benzo(1,3)dioxol-5-yl-methyl)-N-methyl- aminomethyl] -nitrobenzene (81) 4 -(7-chloro-2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl) -nitrobenzene (82) 4 -(7,8-dichloro-2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl)-nitrobenzene I (83) 4-(7-methoxy-2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl) -nitrobenzene (84) 4-(7-methyl-2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl) -nitrobenzene (85) 4-(7,8-dimethoxy-2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl)-nitrobenzene (86) 4-(6,7-dichloro-l,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) -nitrobenzene (87) 4-(6,7-dimethyl-1,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) -nitrobenzene (88) 4-(6-chloro-l,2,3,4-tetrahydro-isoquinolin-2-yl-methyl)-nitrobenzene (89) 4-(7-chloro-l,2,3,4-tetrahydro-isoquinolin-2-yl-methyl)-nitrobenzene (90) 4-(6-methoxy-l,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) nitrobenzene (91) 4-(7-methoxy-l,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) nitrobenzene (92) 4 -[(2,3,4,5-tetrahydro-azepino(4,5-b)pyrazin-3-yl)- methyl]-nitrobenzene (93) 4 - [ (7-amino-2,3,4,5-tetrahydro-azepino(4,5-b)pyrazin-3-yl)-methyl]-nitrobenzene (94) 4 - [ (2-amino-5,6,7,8 -tetrahydro-azepino(4,5-d)thiazol-6-yl)-methyl]-nitrobenzene (95) 4-[(5,6,7,8-tetrahydro-azepino(4,5-d)thiazol-6-yl)-methyl]-nitrobenzene Example XV 4-(1.l-dioxo-thiomorpholin-4-vl-methvl)-nitrobenzene 6.0 g of 4-(thiomorpholin-4-yl-methyl)-nitrobenzene are dissolved in 100 ml of methylene chloride and 10.3 g of meta-chloroperbenzoic acid are slowly added. After a further 3 hours stirring at room temperature the precipitate obtained is filtered off.

Yield: 6.2 g (91 % of theory) Rf value: 0.5 (silica gel, methylene chloride/methanol = 1:1) C1XH14N204S Mass spectrum: m/z = 270 [M+] The following compound is prepared analogously to Example XV: (1) 4-(l-oxo-thiomorpholin-4-yl-methyl)-nitrobenzene Example XVI 4-TN-(3-amino-propyl)-N-methvlsulphonvl-aminol -nitrobenzene 9.5 g of 4-[N-(3-phthalimido-2-yl-propyl)-N-methylsulphonyl-amino]-nitrobenzene are dissolved in 200 ml of ethanol, 11.5 ml of hydrazine hydrate are added and the mixture is stirred for 1.5 hours at 50 °C. After cooling the residue is largely evaporated down, water is added and the solution is extracted with methylene chloride. The organic phase is dried, evaporated down and purified over a silica gel column with methylene chloride/methanol/ammonia 9:1:0.1.

Yield: 2.5 g (39 % of theory) Rf value: 0.2 (silica gel, methylene chloride/methanol = 9:1) C10H15N3O4S ESI mass spectrum: m/z = 272 [M-IT] / The following compound is prepared analogously to Example XVI: (1) 6-[N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino]-3-amino-nitrobenzene Prepared from 6-[N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino]-3-phthalimido-2-yl-nitrobenzene Example XVII 4-(l-methvl-imidazol-2-vl)-nitrobenzene 7.5 g of 4-(imidazol-2-yl)-nitrobenzene are dissolved in 50 ml of dimethylsulphoxide and at 0°C 5.0 g of potassium tert.butoxide are added. After one hour of stirring at room temperature 2.6 ml of methyl iodide are added dropwise and the mixture is stirred for one hour at room temperature. After this time the residue is poured onto ice water and the precipitate formed is suction filtered, washed with water and dried.

Yield: 6.1 g (76 % of theory) Rf value: 0.6 (silica gel, methylene chloride/methanol = 10:1) Melting point: 186-187°C The following compounds are prepared analogously to Example XVII: (1) 4-(l-ethyl-imidazol-2-yl)-nitrobenzene Prepared from 4-(imidazol-2-yl)-nitrobenzene and ethyl iodide (2) 4-(l-benzyl-imidazol-2-yl)-nitrobenzene Prepared from 4-(imidazol-2-yl)-nitrobenzene and benzyl bromide Example XVIII 4- [ (N-(2-(2-methoxy-ethoxy)-ethyl)-N-methyl-amino)-methyl]- nitrobenzene .0 g of 4-methylaminomethyl-nitrobenzene are dissolved in 30 ml of dimethylformamide and 4.6 g of 2-(2-methoxy-ethoxy)-ethyl chloride are added. After six hours' stirring at 100°C the solvent is removed and the residue is taken up in ethyl acetate. The organic phase is washed with water and dried over sodium sulphate. After the elimination of the solvent the residue is purified over an aluminium oxide column (activity 2-3) with toluene/ethyl acetate 5:1 as eluant.

Yield: 2.3 g (29 % of theory) Rf value: 0.5 (aluminium oxide, toluene/ethyl acetate = 5:1) ^-■13^20^2^4 ESI mass spectrum: m/z = 267 [M-HT] Example XIX 4-(N-ethvl-N-tert.butoxycarbonyl-aminomethyl)-nitrobenzene 2.2 g of 4-(ethylaminomethyl)-nitrobenzene are dissolved in 50 ml of ethyl acetate and stirred with 2.6 g of di-tert-butyl. dicarbonate (tert.butoxycarbonyl-anhydride) for 30 minutes at room temperature. Then the solution is washed with water and evaporated down.

Yield: 3.4 g of theory Rf value: 0.3 (silica gel, methylene chloride/methanol = 50 :1) Melting point: 85 °C The following compounds are prepared analogously to Example XIX: (1) 4-[N-(4-chlorophenyl-methyl)-N-tert.butoxycarbonyl-aminomethyl]-nitrobenzene (2) 4-(N-tert.butoxycarbonyl-aminomethyl)-nitrobenzene (3) 4-(N-cyclohexyl-N-tert.butoxycarbonyl-aminomethyl)-nitrobenzene (4) 4-(N-isopropyl-N-tert.butoxycarbonyl-aminomethyl)-nitrobenzene (5) 4-(N-methyl-N-tert.butoxycarbonyl-aminomethyl)-nitrobenzene (6) 4-(N-propyl-N-tert.butoxycarbonyl-aminomethyl)-nitrobenzene (7) 4-(N-butyl-N-tert.butoxycarbonyl-aminomethyl)-nitrobenzene (8) 4-(N-methoxycarbonylmethyl-N-tert.butoxycarbonyl-aminomethyl)-nitrobenzene (9) 4-(N-benzyl-N-tert.butoxycarbonyl-aminomethyl)-nitrobenzene (10) 4- [N-(3-trifluoroacetylamino-propyl)-N-methylsulphonyl-amino]-nitrobenzene Prepared from 4-[N-(3-amino-propyl)-N-methylsulphonyl-amino]-nitrobenzene and trifluoroacetic acid anhydride (11) 4 - [ (4-tert.butoxycarbonyl-piperazin-1-yl)-methyl]-nitrobenzene Example XX 4-(piperidin-l-vl-methvl)-aniline 37.0 g of 4-(piperidin-l-yl-methyl)-nitrobenzene are dissolved in 300 ml of methanol, 8.0 g of Raney nickel are added and the mixture is hydrogenated for 85 minutes with 3 bars of hydrogen at room temperature. The catalyst is filtered off and the filtrate is evaporated down.

Yield: 24.0 g (75 % of theory), Rf value: 0.4 (silica gel, methylene chloride/methanol = 9:1) ^•12^18^2 ESI mass spectrum: m/z = 191 [M+H+] The following compounds are prepared analogously to Example VIII: (1) 4-[(2,6-dimethyl-piperidin-l-yl)-methyl]-aniline (2) N-(2-dimethylamino-ethyl)-N-methylsulphonyl-p-phenylenediamine (3) 3 -(dimethylaminomethyl)-aniline (4) 4-(dimethylaminomethyl)-aniline (5) 4-(2-dimethylamino-ethyl)-aniline (6) 4-[N-(2-dimethylamino-ethyl)-N-acetyl-amino]-aniline (7) 4-[N-(3-dimethylamino-propyl)-N-acetyl-amino]-aniline (8) 4-[N-(2-dimethylamino-ethyl)-N-benzoyl-amino]-aniline (9) 4-[N-(2-dimethylamino-ethyl)-N-propionyl-amino]-aniline (10) 4-[N-(2-dimethylamino-ethyl)-N-butyryl-amino]-aniline i (11) 4-[N-(2-dimethylamino-ethyl)-N-isobutyryl-amino]-aniline (12) 4-(N-tert.butoxycarbonyl-aminomethyl)-aniline (13) 4-(N-ethyl-N-tert.butoxycarbonyl-aminomethyl)-aniline (14) 4-[N-(4-chlorophenyl-methyl)-N-tert.butoxycarbonyl-aminomethyl]-aniline (15) 4-(N-cyclohexyl-N-tert.butoxycarbonyl-aminomethyl)-aniline (16) 4-(N-isopropyl-N-tert.butoxycarbonyl-aminomethyl)-aniline (17) 4-(N-propyl-N-tert.butoxycarbonyl-aminomethyl)-aniline (18) 4-(N-methyl-N-tert.butoxycarbonyl-aminomethyl)-aniline (19) 4-(N-butyl-N-tert.butoxycarbonyl-aminomethyl)-aniline (20) 4-(N-methoxycarbonyl-methyl-N-tert.butoxycarbonyl-aminomethyl)-aniline (21) 4-(N-benzyl-N-tert.butoxycarbonyl-aminomethyl)-aniline (22) 4-(pyrrolidin-1-yl-methyl)-aniline 102 (23) 4- (24) 4- (25) 4- (26) 4- (27) 4- (28) 4- (29) 4- (30) 4- (31) 4- (32) 4- (33) 4- (34) 4- (35) 4- (36) 4- (37) 4- (38) 4- (39) 4- (40) 4- morpholin-4-yl-methyl)-aniline hexamethyleneiminomethyl)-aniline 4-hydroxy-piperidin-1-yl-methyl)-aniline 4-methoxy-piperidin-1-yl-methyl)-aniline 4-methyl-piperidin-l-yl-methyl)-aniline 4-ethyl-piperidin-l-yl-methyl)-aniline 4 -isopropyl-piperidin-l-yl-methyl)-aniline 4-phenyl-piperidin-1-yl-methyl)-aniline 4-benzyl-piperidin-l-yl-methyl)-aniline 4-ethoxycarbonyl-piperidin-1-yl-methyl)-aniline N,N-dipropyl-aminomethyl)-aniline 4 -tert.butoxycarbonyl-piperaz in-1-yl-methyl)-aniline 2-morpholin-4-yl-ethyl)-aniline 2-pyrrolidin-1-yl-ethyl)-aniline 2-piperidin-l-yl-ethyl)-aniline N-propyl-N-benzyl-aminomethyl)-aniline N-(n-hexyl)-N-methyl-aminomethyl]-aniline N-methyl-N-(4-chlorobenzyl)-aminomethyl]-aniline (41) 4-[N-methyl-N-(4-bromobenzyl)-aminomethyl]-aniline (42) 4-[N-methyl-N-(4-methylbenzyl)-aminomethyl]-aniline (43) 4-[N-methyl-N-(4-fluorobenzyl)-aminomethyl]-aniline (44) 4-[N-methyl-N-(3-chlorobenzyl)-aminomethyl]-aniline (45) 4-[N-methyl-N-(3,4-dimethoxybenzyl)-aminomethyl]-anil (46) 4-[N-methyl-N-(4-methoxybenzyl)-aminomethyl]-aniline (47) 4-(N-2,2,2-trifluoroethyl-N-benzyl-aminomethyl)-anili (48) 4-[N-2,2,2-trifluoroethyl-N-(4-chlorobenzyl)-aminomethyl]-aniline (49) 4-(thiomorpholin-4-yl-methyl)-aniline (50) 4-(l-oxo-thiomorpholin-4-yl-methyl)-aniline (51) 4-(1,1-dioxo-thiomorpholin-4-yl-methyl)-aniline (52) 4-(azetidion-l-yl-methyl)-aniline (53) 4-(3,4-dihydropyrrolidin-1-yl-methyl)-aniline (54) 4-(3,4-dihydropiperidin-l-yl-methyl)-aniline (55) 4-(2-methoxycarbonyl-pyrrolidin-l-yl-methyl)-aniline (56) 4-(3,5-dimethyl-piperidin-1-yl-methyl)-aniline (57) 4-(4-phenyl-piperazin-l-yl-methyl)-aniline (58) 4-(4-phenyl-4-hydroxy-piperidin-1-yl-methyl)-aniline (59) 4-[N-(3,4,5-trimethoxy-benzyl)-N-methyl-aminomethyl]- aniline (60) 4-[N-(3,4-dimethoxy-benzyl)-N-ethyl-aminomethyl]-aniline (61) 4-(N-benzyl-N-ethyl-aminomethyl)-aniline (62) 4-[N-(2,6-dichlorobenzyl)-N-methyl-aminomethyl]-aniline (63) 4-[N-(4 -trifluoromethylbenzyl)-N-methyl-aminomethyl]-aniline (64) 4-(N-benzyl-N-isopropyl-aminomethyl)-aniline (65) 4-(N-benzyl-N-tert.butyl-aminomethyl)-aniline (66) 4-(diethylamino-methyl)-aniline (67) 4-(2-diethylamino-ethyl)-aniline (68) 4-(N,N-diisopropyl-aminomethyl)-aniline (69) 4-(N,N-diisobutyl-aminomethyl)-aniline (70) 4-(2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl)-aniline (71) 4-(2,3-dihydro-isoindol-2-yl-methyl)-aniline (72) 4-(6,7-dimethoxy-l,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) -aniline (73) 4-(1,2,3,4-tetrahydro-isoquinolin-2-yl-methyl)-aniline (74) 4-[N-(2-hydroxy-ethyl)-N-benzyl-aminomethyl]-aniline (75) 4-[N-(1-ethyl-pentyl)-N-(pyridin-2-yl-methyl)- aminomethyl]-aniline (76) 4-(piperidin-l-yl-methyl)-3-nitro-aniline (77) 4-(piperidin-l-yl-methyl)-3-amino-aniline (78) 4-(N-benzyl-N-methyl-aminomethyl)-aniline / (79) 4-(N-ethyl-N-methyl-aminomethyl)-aniline (80) 4-(N-phenethyl-N-methyl-aminomethyl)-aniline (81) 4-[N-(3,4-dihydroxy-phenethyl)-N-methyl-aminomethyl]-aniline (82) 4-[N-(3,4,5-trimethoxy-phenethyl)-N-methyl-aminomethyl] -aniline (83) 4-[N-(3,4-dimethoxy-phenethyl)-N-methyl-aminomethyl]-aniline (84) 4-[N-(3,4-dimethoxy-benzyl)-N-methyl-aminomethyl]-aniline (85) 4-[N-(4-chloro-benzyl)-N-methyl-aminomethyl]-aniline (86) 4-[N-(4-bromo-benzyl)-N-methyl-aminomethyl]-aniline (87) 4-[N-(4-fluoro-benzyl)-N-methyl-aminomethyl]-aniline (88) 4-[N-(4-methyl-benzyl)-N-methyl-aminomethyl]-aniline (89) 4-[N-(4-nitro-phenethyl)-N-methyl-aminomethyl]-aniline (90) 4-(N-phenethyl-N-benzyl-aminomethyl)-aniline (91) 4-(N-phenethyl-N-cyclohexyl-aminomethyl)-aniline (92) 4-[N-(2-(pyridin-2-yl)-ethyl)-N-methyl-aminomethyl]-aniline (93) 4-[N-(2-(pyridin-4-yl)-ethyl)-N-methyl-aminomethyl]-aniline (94) 4-[N-(pyridin-4-yl-methyl)-N-methyl-aminomethyl]-aniline (95) 4-(N,N-dibenzylaminomethyl)-aniline (96) 4-[N-(4-nitro-benzyl)-N-propyl-aminomethyl]-aniline (97) 4-[N-benzyl-N-(3-cyano-propyl)-aminomethyl]-aniline (98) 4-(N-benzyl-N-allyl-aminomethyl)-aniline (99) 4-[N-benzyl-N-(2,2,2-trifluoroethyl)-aminomethyl]-aniline (100) 4-[(benzo(1,3)dioxol-5-yl-methyl)-methyl-aminomethyl]-aniline (101) 4-(7-chloro-2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl) -aniline (102) 4-(7,8-dichloro-2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl) -aniline (103) 4-(7-methoxy-2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl) -aniline (104) 4 -(7-methyl-2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl) -aniline (105) 4 -(7,8-dimethoxy-2,3,4,5-tetrahydro-benzo(d)azepin-3-yl methyl)-aniline (10 6) 4 -(6,7-dichloro-l,2,3,4-tetrahydro-isoquinolin-2-yl -methyl)-aniline (107) 4 -(6,7-dimethyl-1,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) -aniline / (108) 4-(6-chloro-l,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) aniline (109) 4-(7-chloro-l,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) aniline (110) 4-(6-methoxy-l,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) -aniline (111) 4-(7-methoxy-l,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) -aniline (112) 4-(2,3,4,5-tetrahydro-azepino(4,5-b)pyrazin-3-yl-methyl) -aniline (113) 4-(7-amino-2,3,4,5-tetrahydro-azepino(4,5-b)pyrazin-3-yl-methyl)-aniline (114) 4-(2-amino-5,6,7,8-tetrahydro-azepino(4,5-d)thiazol-6-yl-methyl)-aniline (115) 4-(5,6,7,8-tetrahydro-azepino(4,5-d)thiazol-6-yl-methyl) -aniline (116) 4-(4-methyl-piperazin-l-yl)-aniline (117) 4-[N-(2-dimethylamino-ethyl)-N-methyl-amino]-aniline (118) 4-[N-(3-dimethylamino-propyl)-N-methyl-amino]-aniline (119) N-(3-dimethylamino-propyl)-N-methylsulphonyl-p-phenylenediamine (120) 4-[(N-dimethylaminocarbonylmethyl-N-methylsulphonyl)-amino]-aniline (121) N-(4-aminophenyl)-N-methyl-methanesulphonamide (122) 4-(imidazol-4-yl)-aniline (123) 4 -(tetrazol-5-yl)-aniline (124) 4-[N-(2-dimethylamino-ethyl)-N-propionyl-amino]-aniline (125) N-(dimethylaminomethylcarbonyl)-N-methyl-p-phenylenediamine (126) N-[(2-dimethylamino-ethyl)-carbonyl]-N-methyl-p-phenylenediamine (127) 4-(N-acetyl-N-dimethylaminocarbonylmethyl)-amino)-aniline (128) N-methylaminocarbonylmethyl-N-methylsulphonyl-p-phenylenediamine (12 9) N-aminocarbonylmethyl-N-methylsulphonyl-p-phenylenediamine (130) 4-(imidazolidin-2,4-dion-5-ylidene-methyl)-aniline (131) 4-(imidazolidin-2,4-dion-5-yl-methyl)-aniline (132) 4-(2-oxo-pyrrolidin-1-yl-methyl)-aniline (13 3) N-cyanomethyl-N-methylsulphonyl-p-phenylenediamine (134) 4-[2-(imidazol-4-yl)-ethyl]-aniline (135) 4-[(4-methyl-piperazin-l-yl)-methyl]-aniline (136) 4-[N-(2-(N-befrzyl-N-methyl-amino)-ethyl)-N-methylsulphonyl-amino]-aniline (137) 4-[N-(3-(N-benzyl-N-methyl-amino)-propyl)-N-methylsulphonyl-amino]-aniline (138) N-cyclohexyl-p-phenylenediamine (139) 4-(pyridin-4-yl-methyl)-aniline (140) 4-(imidazol-1-yl-methyl)-aniline (141) 4-benzyl-aniline (142) N-(3-trifluoroacetylamino-propyl)-N-methylsulphonyl-p-phenylenediamine (143) tert.butyl 4-amino-phenylacetate (144) 4-(imidazol-2-yl)-aniline (145) 4-(1-methyl-imidazol-2-yl)-aniline (146) 4-(l-ethyl-imidazol-2-yl)-aniline (147) 4-(1-benzyl-imidazol-2-yl)-aniline (148) 4-[N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino] amino-aniline (149) 4-[N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino] chloro-aniline (150) 4-[N-(2-dimethylamino-ethyl)-N-acetyl-amino]-3-amino-aniline (151) 4-[N-(2-dimethylamino-ethyl)-N-acetyl-amino]-3-bromo-aniline (152) 4-[2-(4-hydroxy-piperidin-l-yl)-ethyl-amino]-aniline (153) N-(2-dimethylamino-ethyl)-N-ethylsulphonyl-p-phenylenediamine (154) N-(2-dimethylamino-ethyl)-N-propylsulphonyl-p-phenylenediamine (155) N-(2-dimethylamino-ethyl)-N-isopropylsulphonyl-p-phenylenediamine (156) N-(2-dimethylamino-ethyl)-N-butylsulphonyl-p-phenylenediamine (157) N-(2-dimethylamino-ethyl)-N-benzylsulphonyl-p-phenylenediamine (158) N-(2-dimethylamino-ethyl)-N-phenylsulphonyl-p-phenylenediamine (159) 4-((3-hydroxy-pyrrolidin-l-yl)-methyl)-aniline (160) 4-[N-(2-dimethylamino-ethyl)-N-(furan-2-carbonyl)-amino]-aniline - Ill - (161) 4-[N-(2-dimethylamino-ethyl)-N-(2-methoxy-benzoyl)- amino]-aniline (162) 4-[N-(2-dimethylamino-ethyl)-N-(pyridine-3-carbonyl)-amino]-aniline (163) 4-[N-(2-dimethylamino-ethyl)-N-(phenyl-acetyl)-amino]-aniline (164) N-(piperidin-l-yl-methylcarbonyl)-N-methyl-p-phenylenediamine (165) N-(morpholin-4-yl-methylcarbonyl)-N-methyl-p-phenylenediamine (166) N- [ (4-benzyl-piperazin-l-yl)-methylcarbonyl]-N-methyl-p phenylenediamine (167) N-(pyrrolidin-1-yl-methylcarbonyl)-N-methyl-p-phenylenediamine (168) 4-(5-methyl-imidazol-4-yl)-aniline - (169) N- [ (2-dimethylamino-ethyl)-carbonyl]-N-isopropyl-p-phenylenediamine (170) N-[(2-dimethylamino-ethyl)-carbonyl]-N-benzyl-p-phenylenediamine (171) N-(N-aminocarbonylmethyl-N-methyl-amino)-methylcarbonyl)-N-methyl-p-phenylenediamine (172) N-[(N-benzyl-N-methyl-amino)-methylcarbonyl]-N-methyl-p phenylenediamine (173) N-[di-(2-methoxyethyl)-amino-methylcarbonyl]-N-methyl phenylenediamine (174) N-[(2-(4-tert.butoxycarbonyl-piperazin-1-yl)-ethyl)-carbonyl]-N-methyl-p-phenylenediamine (175) N-[ (2-(piperidin-l-yl)-ethyl)-carbonyl]-N-methyl-p-phenylenediamine (176) N- [ (2-(N-benzyl-N-methyl-amino)-ethyl)-carbonyl]-N-methyl-p-phenylenediamine (177) N-(dimethylaminomethylcarbonyl)-N-isopropyl-p-phenylenediamine (178) N-(piperidin-l-yl-methylcarbonyl)-N-isopropyl-p-phenylenediamine (179) N-[(4-tert.butoxycarbonyl-piperazin-1-yl)-methylcarbonyl]-N-isopropyl-p-phenylenediamine (180) N-[(N-benzyl-N-methyl-amino)-methylcarbonyl]-N-benzyl phenylenediamine (181) N-(dimethylaminomethylcarbonyl)-N-benzyl-p-phenylenediamine (182) N-(piperidin-l-yl-methylcarbonyl)-N-benzyl-p-phenylenediamine (183) 4-(1,2,4-triazol-1-yl-methyl)-aniline (184) 4- (1,2,3-triazol-2-yl-methyl)-aniline (185) 4-(1,2,3-triazol-l-yl-methyl)-aniline (186) 4-[(N-ethoxycarbonylmethyl-N-methyl-amino)-methyl]-aniline (187) 4-[(N-aminocarbonylmethyl-N-methyl-amino)-methyl]-aniline (188) 4-(azetidin-l-yl-methyl)-aniline (189) 4- [ (di- (2-metfioxy-ethyl) -amino) -methyl] -aniline (190) 4-t(N-(2-(2-methoxy-ethoxy)-ethyl)-N-methyl-amino)-methyl]-aniline (191) 4-[N-(N-tert.butoxycarbonyl-3-amino-propyl)-N-methyl-aminomethyl] -aniline (192) 4-[(N-(methylcarbamoyl-methyl)-N-methyl-amino)-methyl]-aniline (193) 4-[(N-(dimethylcarbamoyl-methyl)-N-methyl-amino)-methyl]-aniline (194) 4-[(N-propyl-N-methyl-amino)-methyl]-aniline (195) 4-[(N-(2-dimethylamino-ethyl)-N-methyl-amino)-methyl]-aniline (196) 4-[(N-(3-dimethylamino-propyl)-N-methyl-amino)-methyl]-aniline (197) 4-[(N-(2-methoxy-ethyl)-N-methyl-amino)-methyl]-aniline (198) 4-[(N-(2-hydroxy-ethyl)-N-methyl-amino)-methyl]-aniline (199) 4-[(N-(dioxolan-2-yl-methyl)-N-methyl-amino)-methyl]-aniline (200) 4-(3-oxo-piperazin-l-yl-methyl)-aniline (201) N-[di-(2-hydroxyethyl)-amino-methylcarbonyl]-N-methyl-p-phenylenediamine (202) N-[(N-(2-methoxyethyl)-N-methyl-amino)-methylcarbonyl]-N-methyl-p-phenylenediamine (203) N-[(N-(2-dimethylamino-ethyl)-N-methyl-amino)-methylcarbonyl]-N-methyl-p-phenylenediamine (204) N-[(4-methyl-piperazin-l-yl)-methylcarbonyl] -N-methyl-p-phenylenediamine (205) N-[(imidazol-l-yl)-methylcarbonyl]-N-methyl-p-phenylenediamine (206) N-[(phthalimido-2-yl)-methylcarbonyl]-N-methyl-p-phenylenediamine Example XXI 4-(4-hvdroxvmethvl-piperidin-l-vl-methvl-amino)-aniline 1.1 g of 4-(4-ethoxycarbonyl-piperidin-1-yl-methyl-amino)-aniline are suspended in 15 ml of tetrahydrofuran. 175 mg of lithium borohydride are added at room temperature, stirred for 24 h, another 175 mg of lithium borohydride are added and after a further 7.5 hours 15 ml of water are added and the mixture is stirred for 10 minutes. It is extracted three times with 15 ml of ethyl acetate. The combined organic phases are washed with water and saturated saline solution, dried over sodium sulphate and concentrated by rotary evaporation. The residue is purified over a silica gel column with methylene chloride/methanol/ammonia 4:1:0.01 as eluant.

Yield: 200 mg (27 % of theory) Rf value: 0.4 (silica gel, methylene chloride/methanol/ammonia 4:1:0.01) Melting point: 157°C Example XXII methyl 4-methoxvcarbonvlmethvl-3-nitro-benzoate 54.3 g of methyl 3-nitro-benzoate and 2 9.0 g of methyl chloroacetate are dissolved in 100 ml of dimethylformamide and this solution is added dropwise at -10°C to a solution of 78.5 g of potassium-tert. butoxide in 500 ml of dimethylformamide. The mixture is stirred for another 10 minutes at room temperature and after this time the solution is poured onto 350 ml of concentrated hydrochloric acid in 2 1 of ice water. The solution is stirred for 0.5 hours, the precipitate obtained is suction filtered and washed with water. The product is recrystallised from 150 ml of methanol and dried at 40°C in vacuo.

Yield: 48.3 g of (51 % of theory), contains about 20 % of methyl 6-methoxycarbonylmethyl-3-nitro-benzoate Rf value: 0.7 (silica gel, petroleum ether/ethyl acetate = 1:1) Melting point: 65-73 °C The following compound is prepared analogously to Example XXII: (1) ethyl 4-methoxycarbonylmethyl-3-nitro-benzoate Prepared from ethyl 4-thoxycarbonylmethyl-3-nitro-benzoate Example XXIII methvl 2 -indolinone-6-carboxvlate 48.3 g of methyl 4-methoxycarbonylmethyl-3-nitro-benzoate are dissolved in 800 ml of concentrated acetic acid, 5.0 g of palladium on carbon (10%) are added and the solution is hydrogenated for 2.5 hours at room temperature and 50 psi. The catalyst is filtered off and the filtrate is evaporated down. The residue is taken up in 150 ml of tert.-butylmethyl ether, filtered again and dried in vacuo at 100°C.

Yield: 28.6 g (98 % of theory), Rf value: 0.4 (silica gel, methylene chloride/methanol = 10:1) Melting point: 208-211 °C The following compound is prepared analogously to Example XXIII: (1) ethyl 2-indolinone-6-carboxylate Prepared from ethyl 4-methoxycarbonylmethyl-3-nitro-benzoate Example XXIV 1-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl- 2-indolinon e .0 g of ethyl 2-indolinone-6-carboxylate, 49.6 ml of triethyl orthobenzoate and 150 ml of acetic anhydride are stirred for 4 hours at 110°C. After this time the solvent is removed, the residue is recrystallised from petroleum ether and dried in vacuo at 50°C.

Yield: 16.9 g (61 % of theory), Rf value: 0.5 (silica gel, petroleum ether/methylene chloride/ethyl acetate = 5:4:1) Melting point: 98-100°C c22h21no5 The following compounds are prepared analogously to Example XXIV: (1) l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone Prepared from methyl 2-indolinone-6-carboxylate, triethyl orthobenzoate and acetic anhydride (2) l-acetyl-3-(1-ethoxy-l-ethyl-methylene)-6-ethoxycarbonyl-2-indolinone Prepared from ethyl 2-indolinone-6-carboxylate, triethyl orthopropionate and acetic anhydride Preparation of the final compounds: Example 1 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl- me thvlene1 -6 -carbamoyl-2 -indolinone-1 rifluoroacetate 300 mg of resin obtained according to Example II are suspended in 3 ml of dimethylformamide and shaken with 0.2 g of 4-(piperidin-l-yl-methyl)-aniline for 22 hours at 70°C. Then it is filtered off and the resin is washed several times with methylene chloride, methanol and dimethylformamide. Then 1 ml of methanolic ammonia is added for 2 hours in order to eliminate the acetyl group. Then after further washing 4 ml of 10% trifluoroacetic acid in methylene chloride are added during another 6 0 minutes, the resin is separated off and the solution is evaporated down.

Yield: 69 mg Rf value: 0.1 (silica gel, methylene chloride/methanol = 9:1) ^-28-^28^4^2 Mass spectrum: m/z = 452 (m+) The following compounds are prepared analogously to Example 1: (1) 3-Z-(1-Anilino-l-phenyl-methylene)-6-carbamoyl-2-indolinone Prepared from the resin obtained according to Example II and aniline ^22^17^3®2 Mass spectrum: m/z = 355 (m+) (2) 3-Z-[1-(4-dimethylaminomethyl-anilino)-1-phenyl-methylene] -6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and 4-dimethylaminomethyl-aniline C25H24N402 Mass spectrum: m/z = 412 (m+) (3) 3-Z-[1-(4-(2-diethylamino-ethyl)-anilino)-1-phenyl-methylene] -6 -carbamoyl-2-indolinone-1ri fluoroacetate Prepared from the resin obtained according to Example II and 4-(2-diethylamino-ethyl)-aniline c28h30n4o2 Mass spectrum: m/z = 454 (m+) (4) 3-Z- [1- (4- (morpfiolin-4-yl-methyl) -anilino) -1-phenyl-methylene ]-6-carbamoyl-2-indolinone-1ri fluoroacetate Prepared from the resin obtained according to Example II and 4-(morpholin-4-yl-methyl)-aniline Rf value: 0.50 (silica gel, methylene chloride/methanol = 4:1) c27h26n403 Mass spectrum: m/z = 454 (m+) (5) 3-Z-[1-(4-(l-oxo-thiomorpholin-4-yl-methyl)-anilino)- 1-phenyl-methylene]-6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and 4-(l-oxo-thiomorpholin-4-yl-methyl)-aniline Rf value: 0.30 (silica gel, methylene chloride/methanol = 9:1) c27h26n403s Mass spectrum: m/z = 486 (m+) (6) 3-Z-[l-(4-(l,1-dioxo-thiomorpholin-4-yl-methyl)-anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and 4-(1,1-dioxo-thiomorpholin-4-yl-methyl)-aniline Rf value: 0.3 0 (silica gel, methylene chloride/methanol = 9:1) c27h26n4o4s Mass spectrum: m/z = 502 (m+) (7) 3-Z-[1-(4-(benzylaminomethyl)-anilino)-1-phenyl-methylene ]-6 -carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and 4-[N-(phenyl-methyl)-N-tert.butoxycarbonyl-aminomethyl]-aniline Rf value: 0.40 (silica gel, methylene chloride/methanol = 4:1) c30h26n4o2 Mass spectrum: m/z = 474 (m+) (8) 3-Z- [1-(4-(amino-methyl)-anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone-tri fluoroacetate Prepared from the resin obtained according to Example II and 4-(N-tert.butoxycarbonyl-aminomethyl)-aniline Rf value: 0.10 (silica gel, methylene chloride/methanol = 4:1) *--23^20^4^2 Mass spectrum: m/z = 3 84 (m+) (9) 3-Z-[1-(4-(2,6-dimethylpiperidin-1-yl-methyl)-anilino)- 1-phenyl-methylene]-6-carbamoyl-2 -indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and 4-(2,6-dimethylpiperidin-1-yl-methyl)-aniline Rf value: 0.45 (silica gel, methylene chloride/methanol = 4:1) c30h32N4o2 Mass spectrum: m/z = 480 (m+) (10) 3-Z- [1-(4-(pyrrolidin-1-yl-methyl)-anilino)-1-phenyl-methylene ]-6 -carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and 4-(pyrrolidin-l-yl-methyl)-aniline Rf value: 0.15 (silica gel, methylene chloride/methanol = 4:1) c27h26n402 Mass spectrum: m/z = 438 (m+) (11) 3-Z-[1-(3-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and 3-dimethylaminomethyl-aniline Rf value: 0.23 (silica gel, methylene chloride/methanol = 4:1) C25H24N4O2 Mass spectrum: m/z = 412 (m+) (12) 3-Z-[1-(3-(N-methyl-N-ethyl-aminomethyl)-anilino)- 1-phenyl-methylene]-6-carbamoyl-2 -indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and 3-(N-methyl-N-ethyl-aminomethyl)-aniline Rf value: 0.23 (silica gel, methylene chloride/methanol = 4:1) C26H26N402 Mass spectrum: m/z = 426 (m+) (13) 3-Z-[1-(3-(methylaminomethyl)-anilino)-1-phenyl-methylene] -6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and 4-(N-tert.butoxycarbonyl-N-methyl-aminomethyl)-aniline Rf value: 0.06 (silica gel, methylene chloride/methanol = 4:1) ^-24^22^4^2 Mass spectrum: m/z = 3 99 (m+H+) (14) 3-Z-[1-(3-hydroxymethyl-anilino)-1-phenyl-methylene]-6-carbamoyl-2 -indolinone Prepared from the resin obtained according to Example II and 3-amino-benzyl alcohol Rf value: 0.7 (silica gel, methylene chloride/methanol = 4:1) C23H19N3O3 Mass spectrum: m/z = 385 (m+) (15) 3-Z-[1-(4-(methoxycarbonylmethyl-aminomethyl)-anilino)- 1-phenyl-methylene]-6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and 4-(N-methoxycarbonylmethyl-N-tert.butoxycarbonyl-aminomethyl)-aniline Rf value: 0.40 (silica gel, methylene chloride/methanol = 9:1) C26H24N404 Mass spectrum: m/z = 457 (m+H+) (16) 3-Z-[1-(4-(N-methylsulphonyl-N-(dimethylaminocarbonylmethyl) -amino)-anilino)-1-phenyl-methylene]-6-carbamoyl- 2-indolinone Prepared from the resin obtained according to Example II and 4-(N-methylsulphonyl-N-(dimethylaminocarbonylmethyl)-amino)-aniline Rf value: 0.4 0 (silica gel, methylene chloride/methanol = 9:1) *-27^27^5^5^ Mass spectrum: m/z ± 533 (m+) (17) 3-Z-[1-(4-(N-acetyl-aminomethyl)-anilino)-1-phenyl-methylene]-6 -carbamoyl-2-indolinone Prepared from the resin obtained according to Example II and 4-(N-acetyl-aminomethyl)-aniline Rf value: 0.70 (silica gel, methylene chloride/methanol = 4:1) C25H22N4O3 Mass spectrum: m/z = 426 (m+) (18) 3-Z-[1-(3,4-dimethoxy-anilino)-1-phenyl-methylene]-6 -carbamoyl-2-indolinone Prepared from the resin obtained according to Example II and 3,4-dimethoxy-aniline Rf value: 0.40 (silica gel, methylene chloride/methanol = 9:1) ^24^-21^304 Mass spectrum: m/z = 415 (m+) (19) 3-Z- [1-(4-(morpholin-4-yl)-anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and 4-morpholin-4-yl-aniline Rf value: 0.20 (silica gel, methylene chloride/methanol = 9:1) C26H24N403 Mass spectrum: m/z = 440 (m+) (20) 3-Z-[1-(4-acetylamino-anilino)-1-phenyl-methylene]-6-carbamoyl-2 -indolinone Prepared from the resin obtained according to Example II and 4-acetylamino-aniline Rf value: 0.25 (silica gel, methylene chloride/methanol = 9:1) C24H20N4O3 Mass spectrum: m/z = 412 (m+) (21) 3-Z-[1-(4-amino-anilino)-1-phenyl-methylene]-6-carbamoyl-2 -indolinone Prepared from the resin obtained according to Example II and 4 -amino-ani1ine Rf value: 0.40 (silica gel, methylene chloride/methanol = 9:1) ^■-22^18^4 02 Mass spectrum: m/z = 370 (m+) (22) 3-Z-[1-(4-N-methyl-N-acetyl-amino-anilino)-1-phenyl-methylene] -6-carbamoyl-2 -indolinone Prepared from the resin obtained according to Example II and 4-(N-methyl-N-acetyl-amino)-aniline ^25^22^4^3 Mass spectrum: m/z = 426 (m+) (23) 3-Z-[1-(4-ethoxycarbonyl-anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone Prepared from the resin obtained according to Example II and ethyl 4-amino-benzoate C2SH21N304 Mass spectrum: m/z = 427 (m+) (24) 3-Z-[1-(4-carboxy-anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone Prepared from the resin obtained according to Example II and 4-amino-benzoic acid Rf value: 0.11 (silica gel, methylene chloride/methanol = 9:1) C23H17N3O4 Mass spectrum: m/z = 398 (m-H+) (25) 3-Z-[1-(4-benzylcarbamoyl-anilino)-1-phenyl-methylene]-6 -carbamoyl-2 -indolinone Prepared from the resin obtained according to Example II and 4-amino-benzoic acid-benzylamide Rf value: 0.21 (silica gel, methylene chloride/methanol = 9:1) C30H24N4O3 Mass spectrum: m/z = 488 (m+) (26) 3-Z-[1-(eyelohexyl-amino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone Prepared from the resin obtained according to Example II and cyclohexylamine Rf value: 0.60 (silica gel, methylene chloride/methanol = 9:1) ^"22^23-^3^2 Mass spectrum: m/z = 361 (m+) (27) 3-Z-[1-(4-amino-cyclohexyl-amino)-1-phenyl-methylene]-6 -carbamoyl-2-indolinone-tri fluoroacetate Prepared from the resin obtained according to Example II and 4-amino-cyclohexylamine ^"22^24^4^2 Mass spectrum: m/z = 376 (m+) (28) 3-Z-[1-(N-methyl-piperidine-4-yl-amino)-1-phenyl-methylene] -6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and 4-amino-1-methyl-piperidine Rf value: 0.15 (silica gel, methylene chloride/methanol = 4:1) C22H24N402 Mass spectrum: m/z = 376 (m+) (29) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-methyl-methylene]-6-carbamoyl-2 -indolinone-trifluoroacetate Prepared from the resin obtained according to Example 11(2) and 4-(piperidin-l-yl-methyl)-aniline Rf value: 0.3 0 (silica gel, methylene chloride/methanol = 4:1) *-"23^26^4(32 Mass spectrum: m/z = 390 (m+) (30) 3-Z-[1-(3-dimethylaminomethyl-anilino)-1-methyl-methylene]-6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example 11(2) and 3-dimethylaminomethyl-aniline Rf value: 0.51 (silica gel, methylene chloride/methanol = 4:1) C20H22N4O2 ' Mass spectrum: m/z = 351 (m+H+) (31) 3-Z-[1-(4-(N-methyl-N-benzyl-aminomethyl)-anilino)- 1-methyl-methylene]-6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example 11(2) and 4-(N-methyl-N-benzyl-aminomethyl)-aniline Rf value: 0.73 (silica gel, methylene chloride/methanol = 4:1) c26h26n4o2 Mass spectrum: m/z = 426 (m+) (32) 3-Z-[1-(4-(N-methylsulphonyl-N-(2-dimethylamino-ethyl)-amino)-anilino)-1-methyl-methylene]-6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example 11(2) and 4-(N-methylsulphonyl-N-(2-dimethylamino-ethyl)-amino)-aniline C22H27Ns04S Mass spectrum: m/z = 458 (m+H+) (33) 3-Z-[1-(4-chloro-anilino)-1-methyl-methylene]-6-carbamoyl-2 -indolinone Prepared from the resin obtained according to Example 11(2) and 4-chloro-aniline Rf value: 0.10 (silica gel, methylene chloride/methanol = 9:1) C17H14C1N302 Mass spectrum: m/z = 327/329 (m+) (34) 3-Z-[1-(3-chloro-anilino)-1-methyl-methylene]-6-carbamoyl-2 -indolinone Prepared from the resin obtained according to Example 11(2) and 3-chloro-aniline Rf value: 0.11 (silica gel, methylene chloride/methanol = 9:1) c17h14c1n302 Mass spectrum: m/z = 327/329 (m+) (35) 3-Z-[1-(4-methoxycarbonyl-anilino)-1-methyl-methylene]-6 -carbamoyl-2-indolinone Prepared from the resin obtained according to Example 11(2) and methyl 4-amino-benzoate Rf value: 0.11 (silica gel, methylene chloride/methanol = 9:1) Ci9H17N304 Mass spectrum: m/z = 351 (m+) (36) 3-Z-[1-(4-carboxy-anilino)-1-methyl-methylene]-6-carbamoyl-2 -indolinone Prepared from the resin obtained according to Example 11(2) and 4-amino-benzoic acid C18H15N304 Mass spectrum: m/z = 336 (m-H+) (37) 3-Z-[1-(4-methyl-3-nitro-anilino)-1-methyl-methylene]-6-carbamoyl-2-indolinone Prepared from the resin obtained according to Example 11(2) and 4-methyl-3-nitro-aniline Rf value: 0.82 (silica gel, methylene chloride/methanol = 4:1) c18h16n4o4 Mass spectrum: m/z = 352 (m+) (38) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-propyl-methylene]-6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example 11(4) and 4-(piperidin-l-yl-methyl)-aniline Rf value: 0.37 (silica gel, methylene chloride/methanol = 4:1) *-25^30^4^2 Mass spectrum: m/z = 418 (m+) (39) 3-Z-[1-(3-dimethylaminomethyl-anilino)-1-propyl-methylene]-6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example 11(4) and 3-dimethylaminomethyl-aniline Rf value: 0.42 (silica gel, methylene chloride/methanol = 4:1) C22H26N402 Mass spectrum: m/z = 3 78 (m+) (40) 3-Z-[1-(4-(N-methyl-N-benzyl-aminomethyl)-anilino)-1-pro-pyl-methylene]-6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example 11(4) and 4-(N-methyl-N-benzyl-aminomethyl)-aniline Rf value: 0.81 (silica gel, methylene chloride/methanol = 4:1) ^-28^30^4®2 Mass spectrum: m/z = 454 (m+) (41) 3-Z-[1-(4-(N-methylsulphonyl-N-(2-dimethylamino-ethyl)-amino)-anilino)-1-propyl-methylene]-6-carbamoyl-2-indolinone-trif luoroacetate Prepared from the resin obtained according to Example 11(4) and 4-(N-methylsulphonyl-N-(2-dimethylamino-ethyl)-amino)-aniline Rf value: 0.59 (silica gel, methylene chloride/methanol = 4:1) ^"■24^31^5^4® Mass spectrum: m/z = 486 (m+H+) (42) 3-Z-[1-(4-chloro-anilino)-1-propyl-methylene]-6-carbamoy1-2 -indolinone Prepared from the resin obtained according to Example 11(4) and 4-chloro-aniline Rf value: 0.17 (silica gel, methylene chloride/methanol = 9:1) ^•19^18 C1N302 Mass spectrum: m/z = 355/357 (m+) (43) 3-Z-[1-(3-chloro-anilino)-1-propyl-methylene]-6-carbamoyl-2-indolinone Prepared from the resin obtained according to Example 11(4) and 3-chloro-aniline Rf value: 0.12 (silica gel, methylene chloride/methanol = 9:1) C19H18C1N302 Mass spectrum: m/z = 355/357 (m+) (44) 3-Z-[1-(4-methoxycarbonyl-anilino)-1-propyl-methylene]-6-carbamoyl-2 -indolinone Prepared from the resin obtained according to Example 11(4) and methyl 4-amino-benzoate Rf value: 0.8 (silica gel, methylene chloride/methanol = 4:1) C21H21N304 Mass spectrum: m/z = 379 (m+) (45) 3-Z-[1-(4-carboxy-anilino)-1-propyl-methylene]-6 -carbamoyl-2 -indolinone Prepared from the resin obtained according to Example 11(4) and 4-amino-benzoic acid *--20^19^3^4 Mass spectrum: m/z = 364 (m-H+) (46) 3-Z-[1-(4-methyl-3-nitro-anilino)-1-propyl-methylene]-6 -carbamoyl-2-indolinone Prepared from the resin obtained according to Example 11(4) and 4-methyl-3-nitro-aniline Rf value: 0.86 (silica gel, methylene chloride/methanol = 4:1) *"•20^-2 0-^4 O4 Mass spectrum: m/z = 380 (m+) Example 2 3-Z- [1-(3-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene1-6-carbamoyl-2-indolinone-trifluoroacetate 2.0 g of resin obtained according to Example II are reacted analogously to Example 1 with 2.0 g of 3-aminobenzyl alcohol in 20 ml of dimethylformamide for 22 hours at 70° C. Then the solvent is suction filtered and the resin is washed several times with dimethylformamide and methylene chloride. Then 200 mg of the moist charged resin are suspended in 2 ml of methylene chloride and left to stand with 0.2 ml of methanesulphonic acid chloride and 0.1 ml of triethylamine for 2 hours at room temperature. Then the resin is washed several times with methylene chloride, suspended in 2 ml of methylene chloride and combined with 0.2 ml of piperidine. After 1 hour the resin is washed with methylene chloride and dimethylformamide and then treated with trifluoroacetic acid analogously to Example 1.

Yield: 15 mg Rf value: 0.3 0 (silica gel, methylene chloride/methanol = 4:1) c28h28n4o2 Mass spectrum: m/z = 452 (m+) The following compounds are prepared analogously to Example 2: (1) 3-Z-[1-(3-(diethylaminomethyl)-anilino)-1-phenyl-methylene] -6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and diethylamine Rf value: 0.80 (silica gel, methylene chloride/methanol = 4:1) *-27^28^4^2 Mass spectrum: m/z = 440 (m+) (2) 3-Z-[1-(3-(benzylaminomethyl)-anilino)-1-phenyl-methylene] -6-carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and benzylamine Rf value: 0.80 (silica gel, methylene chloride/methanol = 4:1) c30h26n4o2 Mass spectrum: m/z = 474 (m+) (3) 3-Z-[1-(3-(N-methyl-N-benzyl-aminomethyl)-anilino)- 1-phenyl-methylene]-6 -carbamoyl-2 -indolinone-tri fluoroacetate Prepared from the resin obtained according to Example II and N-methyl-benzylamine Rf value: 0.80 (silica gel, methylene chloride/methanol = 4:1) ^-31^28^4^2 Mass spectrum: m/z = 488 (m+) (4) 3-Z-[1-(3-(butylaminomethyl)-anilino)-1-phenyl-methylene]-6 -carbamoyl-2-indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and butylamine Rf value: 0.40 (silica gel, methylene chloride/methanol = 4:1) C27H28N402 Mass spectrum: m/z = 440 (m+) (5) 3-Z-[1-(3-(aminomethyl)-anilino)-1-phenyl-methylene]-6 -carbamoyl-2 -indolinone-trifluoroacetate Prepared from the resin obtained according to Example II and ammonia c23h2 0n4o2 Mass spectrum: m/z = 385 (m+H+) (6) 3-Z-[1-(3-(N-(3-dimethylaminopropyl)-N-methyl-aminomethyl) -anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone-trif luoroacetate Prepared from the resin obtained according to Example II and l-dimethylamino-3-methylaminopropane Rf value: 0.67 (silica gel, methylene chloride/methanol = 4:1) ^"•29^33^5^2 Mass spectrum: m/z = 484 (m+H+) (7) 3-Z-[1-(3-(N-(2-dimethylaminoethyl)-N-methyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone-trif luoroacetate Prepared from the resin obtained according to Example II and 1-dimethylamino-2-methylaminoethane Rf value: 0.40 (silica gel, methylene chloride/methanol = 4:1) 8-^31^5^2 Mass spectrum: m/z = 470 (m+H+) Example 3 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl- methvlene1 -6-ethoxycarbonyl-2-indolinone 1.5 g of l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 1.1 g of 4-(piperidin-l-yl-methyl) -aniline are dissolved in 15 ml of dimethylformamide and stirred for 45 minutes at 100°C. After cooling 5.0 ml of piperidine are added and the mixture is stirred for another 3 hours at room temperature. The solvent is removed and the residue purified over an aluminium oxide column (activity: 2-3) with methylene chloride/ethanol (100:3) as eluant.

Yield: 1.1 g (58% of theory), Rf value: 0.5 (aluminium oxide, methylene chloride/ethanol = 100:3) C3OH31N303 Mass spectrum: m/z = 481 [M+] The following compounds are prepared analogously to Example 3 : (1) 3-Z-[1-(4-bromo-anilino)-1-phenyl-methylene]-6-ethoxy-carbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-bromoaniline Rf value: 0.4 (silica gel, toluene/ethyl acetate = 5:1) C24H19BrN203 Mass spectrum: m/z = 462/464 [M+] (2) 3-Z-[1-(3-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] - 6 -ethoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 3-(dimethylaminomethyl)-aniline Rf value: 0.5 (aluminium oxide, methylene chloride/ethanol = 30:1) c27h27n3o3 ESI mass spectrum: m/z = 442 [M+H+] (3) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(dimethylaminomethyl)-aniline Rf value: 0.7 (aluminium oxide, ethyl acetate/ethanol = 20:1) ^-27^-27^303 ESI mass spectrum: m/z = 442 [M+H+] (4) 3-Z-[1-(4-[(2,6-dimethyl-piperidin-1-yl)-methyl]-anilino 1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6- ethoxycarbonyl-2-indolinone and 4-[(2,6-dimethyl-piperidin-1 yl)-methyl]-aniline Rf value: 0.6 (silica gel, methylene chloride/ethanol = 5:1) C32H35N303 Mass spectrum: m/z = 509 [M+] (5) 3-Z-[1-(4-(2-dimethylamino-ethyl)-anilino)-1-phenyl-methylene ] -6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(2-dimethylamino-ethyl)-aniline Rf value: 0.2 (silica gel, methylene chloride/ethanol = 5:1) C28H29N3O3 Mass spectrum: m/z = 455 [M+] (6) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-aniline Rf value: 0.4 (aluminium oxide, methylene chloride/ethanol = 20:1) ^30^32-^4(34 Mass spectrum: m/z = 512 [M+] (7) 3-Z-[1-(4-tert.butyloxycarbonyl-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-tert.butyloxycarbonyl-aniline Rf value: 0.4 (aluminium oxide, methylene chloride/ethanol = 40:1) C29H28N2Os Mass spectrum: m/z = 484 [M+] (8) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-aniline Rf value: 0.2 (aluminium oxide, methylene chloride/ethanol = 40:1) C31H34N404 Mass spectrum: m/z = 526 [M+] (9) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and N-(2-dimethylamino-ethyl)-N-methylsulphonyl-p-phenylenediamine Rf value: 0.3 (aluminium oxide, methylene chloride/ethanol = 40:1) C29H32N4OsS Mass spectrum: m/z = 548 [M+] (10) 3-Z- [1-(4-(4-methyl-piperazin-l-yl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(4-methyl-piperazin-l-yl)-aniline Rf value: 0.3 (aluminium oxide, ethyl acetate) *-"29^30^4 *~*3 ESI mass spectrum: m/z = 483 [M+H+] (11) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6- ethoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl)-N-methyl-amino)-aniline Rf value: 0.5 (aluminium oxide, methylene chloride/ethanol = 20 :1) *-"29^32^4^3 ESI mass spectrum: m/z = 4 85 [M+H+] (12) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(N-(3-dimethylamino-propyl)-N-methyl-amino)-aniline Rf value: 0.5 (aluminium oxide, ethyl acetate) C30H34N4O3 ESI mass spectrum: m/z = 499 [M+H+] (13) 3-Z-[1-(4-(N-methyl-acetylamino)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-amino-N-methyl-acetanilide Rf value: 0.3 (silica gel, methylene chloride/ethanol = 15:1) C27H25N3O4 Mass spectrum: m/z = 455 [M+] (14) 3-Z-[1-(4-(N-methyl-methylsulphonylamino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and N-(4-aminophenyl)-N-methyl-methanesulphonamide Rf value: 0.8 (aluminium oxide, ethyl acetate) C26H25N3OsS Mass spectrum: m/z = 4 91 [M+] (15) 3-Z- [1- (4- (N- (3-dimethylamino-propyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and N-(3-dimethylamino-propyl)-N-methylsulphonyl-p-phenylenediamine Rf value: 0.6 (silica gel, methylene chloride/ethanol/ammonia = 5:2:0.01) C30H34N4O5S ESI mass spectrum: m/z = 563 [M+H+] (16) 3-Z-[1-(4-(N-dimethylaminocarbonylmethyl-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-e t hoxyc a rbony1-2 -indo1inone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(N- dimethylaminocarbonylmethyl-N-methylsulphonyl)-amino)-aniline Rf value: 0.6 (silica gel, methylene chloride/ethanol = 10:1) C29H30N4O6S ESI mass spectrum: m/z = 561 [M-H~] (17) 3-Z-[1-(4-(imidazol-4-yl)-anilino)-1-phenyl-methylene]-6 ethoxycarbonyl - 2 - inciol inone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(imidazol-4-yl)-aniline Rf value: 0.5 (silica gel, methylene chloride/ethanol/ammonia = 10:1:0.01) ^-2 7^2 2^4 O 3 Mass spectrum: m/z = 450 [M+] (18) 3-Z-[1-(4-(tetrazol-5-yl)-anilino)-1-phenyl-methylene]-6 ethoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(tetrazol-5-yl)-aniline Rf value: 0.5 (silica gel, methylene chloride/ethanol = 5:1) C25H20N6O3 ESI mass spectrum: m/z = 451 [M-H"] (19) 3-Z-[1-(4-(N-benzyl-N-methyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(N-benzyl-N-methyl-aminomethyl) -aniline Rf value: 0.4 (silica gel, methylene chloride/ethanol = 10:1) C33H31N303 ESI mass spectrum: m/z = 516 [M-H"] (20) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-propionyl-amino)-aniline)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-[N-(2-dimethylamino-ethyl)-N-propionyl-amino]-aniline Rf value: 0.2 (silica gel, methylene chloride/ethanol = 5:1) c31h34n4o4 ESI mass spectrum: m/z = 525 [M-H"] (21) 3-Z-[1-(4-(pyrrolidin-1-yl-methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(pyrrolidin-1-yl-methyl)-aniline Rf value: 0.1 (silica gel, methylene chloride/ethanol = 5:1) C29H29N3O3 ESI mass spectrum: m/z = 466 [M-H"] (22) 3-Z-[1-(4-(N-methyl-N-phenethyl-aminomethyl)-anilino)-1-phenyl-methylene]-6 -ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(N-phenethyl-N-methyl-aminomethyl) -aniline Rf value: 0.4 (silica gel, methylene chloride/ethanol = 10:1) C34H33N3O3 ESI mass spectrum: m/z = 530 [M-H"] (23) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and N-dimethylaminomethylcarbonyl N-methyl-p-phenylenediamine Rf value: 0.1 (silica gel, methylene chloride/ethanol = 10:1) C29H30N4O4 ESI mass spectrum: m/z = 497 [M-H"] (24) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-ethylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and N-(2-dimethylamino-ethyl)-N ethylsulphonyl-p-phenylenediamine Rf value: 0.6 (silica gel, methylene chloride/ethanol = 5:1) C30H34N4O5S ESI mass spectrum: jh/z = 561 [M-H"] (25) 3-Z-[1-(4-(N-tert.butoxycarbonyl-N-ethyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and 4-(N-tert.butoxycarbonyl-N-ethyl-aminomethyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 10: C32H35N3Os ESI mass spectrum: m/z = 540 [M-H"] (26) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-ethyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-ethyl-methylene)-6-ethoxycarbonyl-2-indolinone and 4-(piperidin-l-yl-methyl)-aniline Rf value: 0.9 (silica gel, methylene chloride/ethanol = 5:1) ^-■26^31^3^3 ESI mass spectrum: m/z = 432 [M-H"] (27) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl amino)-anilino)-1-ethyl-methylene]-6-ethoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-ethyl-methylene)-6-ethoxycarbonyl-2-indolinone and N-(2-dimethylamino-ethyl)-N methylsulphonyl-p-phenylenediamine Rf value: 0.3 (silica gel, methylene chloride/ethanol = 5:1) C25H32N405S ESI mass spectrum: m/z = 499 [M-H~] (28) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(dimethylaminomethyl)-aniline Rf value: 0.6 (silica gel, methylene chloride/methanol = 5:1) c26h25n303 ESI mass spectrum: m/z = 428 [M+H+] (29) 3-Z-[1-(4-[(2,6-dimethyl-piperidin-1-yl)-methyl]-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-[(2,6-dimethyl-piperidin-1 yl)-methyl]-aniline Rf value: 0.5 (RP 8, methanol/five percent saline solution = 4:1) C31H33N3O3 ESI mass spectrum: m/z = 496 [M+H+] (30) 3-Z-[l-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(2-dimethylamino-ethyl)-N-methylsulphonyl-p-phenylenediamine Rf value: 0.6 (silica gel, methylene chloride/methanol = 5:1) C28H3oN405S ESI mass spectrum: m/z = 533 [M-H"] (31) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(3-dimethylamino-propyl)-N-methylsulphonyl-p-phenylenediamine Rf value: 0.5 (aluminium oxide, methylene chloride/methanol = 30:1) *-29^32^4^5^ ESI mass spectrum: m/z = 547 [M-H"] (32) 3-Z-[1-(4-(N-dimethylaminocarbonylmethyl-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl -2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-dimethylaminocarbonyl-methyl-N-methylsulphonyl)-amino)-aniline Rf value: 0.5 (aluminium oxide, methylene chloride/methanol = 20 :1) ^"28^28^4^6® ESI mass spectrum: m/z = 547 [M-H"] (33) 3-Z-[1-(4-(N-acetyl-N-dimethylaminocarbonylmethyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-acetyl-N-dimethylaminocarbonylmethyl)-amino)-aniline Rf value: 0.6 (silica gel, methylene chloride/methanol = 10:1) ^--29^28^405 ESI mass spectrum: m/z = 511 [M-H"] (34) 3-Z-[1-(4-(N-dimethylaminocarbonylmethyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-dimethylaminocarbonyl-methyl)-amino)-aniline Rf value: 0.6 (aluminium oxide, methylene chloride/methanol = :1) C27H26N404 ESI mass spectrum: m/z = 469 [M-H"] (35) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(3-dimethylamino-propyl)-N acetyl-p-phenylenediamine Rf value: 0.5 (aluminium oxide, methylene chloride/methanol = 20:1) C30H32N4O4 ESI mass spectrum: m/z = 511 [M-H"] (36) 3-Z-[l-(4-(N-methylaminocarbonylmethyl-N-methylsulphonyl amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-methylaminocarbonylmethyl-N-methylsulphonyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 10:1) C27H26N4OsS ESI mass spectrum: m/z = 533 [M-H"] (37) 3-Z-[1-(4-((imidazolidin-2,4-dion-5-ylidene)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6- trie thoxycarbonyl-2-indolinone and 4-( (imidazolidin-2 , 4-dion-5-ylidene)-methyl)-aniline Rf value: 0.4 (silica gel, methylene chloride/methanol = 10:1) C27H20N4O5 ESI mass spectrum: m/z = 479 [M-H"] (38) 3-Z-[1-(4-(N-((2-dimethylamino-ethyl)-carbonyl)-N-methyl amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-((2-dimethylamino-ethyl)-carbonyl)-N-methyl-p-phenylenediamine Rf value: 0.5 (aluminium oxide, methylene chloride/methanol = :1) C29H30N4O4 ESI mass spectrum: m/z = 497 [M-H"] (39) 3-Z- [1-(4-(N-t^rt.butoxycarbonyl-aminomethyl)-anilino)-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-tert.butoxycarbonyl-aminomethyl)-aniline Rf value: 0.3 (aluminium oxide, methylene chloride/methanol = 20:1) ^29^-29^3®5 ESI mass spectrum: m/z = 498 [M-H"] (40) 3-Z-[1-(4-(2-oxo-pyrrolidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(2-oxo-pyrrolidin-l-yl-methyl)-aniline Rf value: 0.3 (silica gel, methylene chloride/methanol = 20:] ^-28^25^3^4 ESI mass spectrum: m/z = 466 [M-H"] (41) 3-Z- [1-(4-(N-aminocarbonylmethyl-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-aminocarbonylmethyl-N-methylsulphonyl-p-phenylenediamine Rf value: 0.7 (silica gel, methylene chloride/methanol = 5:1) C26H24N406S ESI mass spectrum: m/z = 519 [M-H"] (42) 3-Z-[1-(4-(thiomorpholin-4-yl-methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(thiomorpholin-4-yl-methyl) -aniline Rf value: 0.4 (silica gel, methylene chloride/methanol = 15:1) ^-•28^27^3^3® ESI mass spectrum: rti/z = 484 [M-H"] (43) 3-Z-[l-(4-(l,1-dioxo-thiomorpholin-4-yl-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(1,1-dioxo-thiomorpholin-4-yl-methyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 10:1) ^-"28^27^3^5® ESI mass spectrum: m/z = 516 [M-H"] (44) 3-Z-[1-(4-(N-cyanomethyl-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-cyanomethyl-N-methylsulphonyl -p-phenylenediamine Rf value: 0.6 (silica gel, methylene chloride/methanol = 10:1) C26H22N405S ESI mass spectrum: m/z = 501 [M-H"] (45) 3-Z-[l-(4-(N-tert.butoxycarbonyl-ethylaminomethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-ethyl-N- tert.butoxycarbonyl-aminomethyl)-ani1ine Rf value: 0.6 (silica gel, methylene chloride/methanol = 10:1) C31H33N3Os ESI mass spectrum: m/z = 526 [M-H"] (46) 3-Z-[1-(4-(N-benzyl-N-methyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-benzyl-N-methyl-aminomethyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 10:1) C-32H29N303 ESI mass spectrum: iti/z = 502 [M-H"] (47) 3-Z-[1-(4-(l-oxo-thiomorpholin-4-yl-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(l-oxo-thiomorpholin-4-yl-methyl) -aniline Rf value: 0.7 (silica gel, methylene chloride/methanol = 10:1) ^-28^27^3048 ESI mass spectrum: m/z = 500 [M-H"] (48) 3-Z-[1-(4-(2-(imidazol-4-yl)-ethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(2-(imidazol-4-yl)-ethyl)-aniline Rf value: 0.4 (silica gel, methylene chloride/methanol = 5:1) ^28^24^03 ESI mass spectrum: m/z = 463 [M-H"] (49) 3-Z- [1-(4-(morpholin-4-yl-methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(morpholin-4-yl-methyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 10:1) ^-28-^27^3^4 ESI mass spectrum: m/z = 468 [M-H"] (50) 3-Z-[1-(4-((4-methyl-piperazin-l-yl)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((4-methyl-piperazin-l-yl)-methyl)-aniline Rf value: 0.4 (silica gel, methylene chloride/methanol 5:1) *-•29^30^4^3 ESI mass spectrum: m/z = 481 [M-H"] (51) 3-Z-[1-(4-((2-(N-benzyl-N-methyl-amino)-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-(N-benzyl-N-methyl-amino) -ethyl)-N-methylsulphonyl-amino)-aniline Rf value: 0.7 (silica gel, methylene chloride/methanol = 10:1) C34H34N405S ESI mass spectrum: m/z = 609 [M-H"] (52) 3-Z-[1-(4-cyclohexylamino-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-cyclohexyl-p-phenylenediamine Rf value: 0.8 (silica gel, methylene chloride/methanol = 10:1) ^gHjgNjOj ESI mass spectrum: m/z = 451 [M-H"] (53) 3-Z-[1-(4-(pyridin-4-yl-methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(pyridin-4-yl-methyl)-aniline Rf value: 0.6 (silica gel, methylene chloride/methanol/ammonia c29h23n3o3 ESI mass spectrum: m/z = 460 [M-H"] (54) 3-Z-[1-(4-(imidazol-1-yl-methyl)-anilino)-1-phenyl-methylene] - 6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(imidazol-1-yl-methyl)-aniline Rf value: 0.4 (silica gel, methylene chloride/methanol/ammonia = 10:1:0.01) ^-27H22-^4®3 ESI mass spectrum: m/z = 449 [M-H"] (55) 3-Z-[1-(4-(imidazol-1-yl-methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(imidazol-1-yl-methyl)-aniline Rf value: 0.4 (silica gel, methylene chloride/methanol/ammonia = 10:1:0.01) c27h22n403 ESI mass spectrum: m/z = 449 [M-H"] (56) 3-Z-[1-(N-methyl-piperidine-4-yl-amino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-amino-1-methyl-piperidine Rf value: 0.3 (silica gel, methylene chloride/methanol = 5:1) c23h25n3o3 ESI mass spectrum: m/z = 390 [M-H"] (57) 3-Z-[1-(4-(imidazol-4-yl-methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(imidazol-4-yl-methyl)-aniline Rf value: 0.2 (silica gel, methylene chloride/methanol = 5:1) ^"•27^22^4^3 ESI mass spectrum: m/z = 449 [M-H"] (58) 3-Z-[1-(4-((4-hydroxy-piperidin-l-yl)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((4-hydroxy-piperidin-l-yl) -methyl)-aniline' Rf value: 0.1 (silica gel, methylene chloride/methanol = 10:1) *--29^29^3^3 ESI mass spectrum: m/z = 482 [M-H"] (59) 3-Z-[1-(4-((4-methoxy-piperidin-l-yl)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((4-methoxy-piperidin-l-yl) -methyl)-aniline Rf value: 0.4 (silica gel, methylene chloride/methanol = 10:1) C30H31N3O4 ESI mass spectrum: m/z = 496 [M-H"] (60) 3-Z-[1-(4-benzyl-anilino)-1-phenyl-methylene] -6-methoxy-carbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-benzyl-aniline R£ value: 0.6 (silica gel, methylene chloride/methanol = 10:1) c30h24n2o3 Melting point: 224°C (61) 3-Z- [1- (4-(N-(3-trifluoroacetylamino-propyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(3-trifluoroacetylamino-propyl)-N-methylsulphonyl-p-phenylenediamine Rf value: 0.5 (aluminium oxide, methylene chloride/methanol = 20 :1) C29H27F3N406S ESI mass spectrum: m/z = 615 [M-H-] (62) 3-Z- [1-(4-tert.butoxycarbonylmethyl-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-ethoxycarbonyl-2-indolinone and tert.butyl 4-aminophenylacetate Rf value: 0.5 (aluminium oxide, ethyl acetate) ^*■30^30^2^5 ESI mass spectrum: m/z = 497 [M-H"] (63) 3-Z-[1-(4-tert.butoxycarbonyl-anilino)-1-ethyl-me t hy1ene]-6-ethoxycarbonyl-2 -indo1inone Prepared from l-acetyl-3-(1-ethoxy-l-ethylmethylen)-6-ethoxycarbonyl-2-indolinone and 4-tert.butoxycarbonyl-aniline Rf value: 0.4 (aluminium oxide, methylene chloride/ethanol = 20 :1) c25h28n2o5 ESI mass spectrum: m/z = 435 [M-H"] (64) 3-Z-[1-(4-(4-tert.butoxycarbonyl-piperazin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(4-tert.butoxycarbonyl-piperazin-l-yl-methyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 10:1) C33H36N405 ESI mass spectrum: m/z = 567 [M-H"] (65) 3-Z-[1-(4-(1-methyl-imidazol-2-yl)-anilino)-1-phenyl-methylene ]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(1-methyl-imidazol-2-yl)-aniline Rf value: 0.6 (silica gel, methylene chloride/methanol = 5:1) C-27H22N403 ESI mass spectrum: m/z = 449 [M-H"] (66) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-3-nitro-anilino)-1-phenyl-methylene]-6-methoxycarbonyl 2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 6-(N-(2-dimethylamino-ethyl) N-methylsulphonyl-amino)-3-amino-nitrobenzene Rf value: 0.6 (silica gel, methylene chloride/methanol = 5:1) C28H29N507S ESI mass spectrum: m/z = 578 [M-H"] (67) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-3-amino-anilino)-1-phenyl-methylene]-6-methoxycarbonyl 2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl) N-methylsulphonyl-amino)-3-amino-aniline Rf value: 0.5 (aluminium oxide, methylene chloride/methanol = :1) C28H31N505S ESI mass spectrum: m/z = 548 [M-H"] (68) 3-Z-[1-(4-((3-(N-benzyl-N-methyl-amino)-propyl)-N-methyl sulphonyl-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(n-(3-(n-benzyl-n-methyl-amino) -propyl)-N-methylsulphonyl-amino)-aniline Rf value: 0.6 (silica gel, methylene chloride/methanol = 10:1) c35h36n4o5s ESI mass spectrum: m/z = 623 [M-H"] (69) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-3-chloro-anilino)-1-phenyl-methylene] -6- methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl) N-methylsulphonyl-amino)-3-chloro-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 10:1) C28H29C1N405S ESI mass spectrum: m/z = 567/569 [M-H"] (70) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N- dimethylaminomethylcarbonyl-N-methyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c28h28n4o4 ESI mass spectrum: m/z = 483 [M-H"] (71) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl) N-acetyl-amino)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C29H30N4O4 ESI mass spectrum: m/z = 497 [M-H"] (72) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-propionyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl) N-propionyl-amino)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) *"30^32^4 04 ESI mass spectrum: m/z = 511 [M-H"] (73) 3-Z- [1-(4-(N-(2-dimethylamino-ethyl)-N-butyryl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6- methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl) N-butyryl-amino)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C3iH34N404 ESI mass spectrum: m/z = 525 [M-H"] (74) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl) -N-isobutyryl-amino) anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6- methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl) N-isobutyryl-amino)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c31h34n4o4 ESI mass spectrum: m/z = 525 [M-H"] (75) 3-Z- [1-(4-(N-(2-dimethylamino-ethyl)-N-benzoyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl) N-benzoyl-amino)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C34H32N4O4 ESI mass spectrum: m/z = 559 [M-H"] (76) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-3-amino-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl) N-acetyl-amino)-3-amino-aniline Rf value: 0.5 (aluminium oxide, methylene chloride/methanol = 20:1) ^-•2 9^31^5 04 ESI mass spectrum: m/z = 512 [M-H"] (77) 3-Z-[1-(4-(4-hydroxymethyl-piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(4-hydroxymethyl-piperidin-1-yl-methyl-amino)-aniline Rf value: 0.3 (silica gel, methylene chloride/methanol = 5:1) C3 0^31-^3^4 ESI mass spectrum: m/z = 496 [M-H"] (78) 3-Z-[1-(4-(2-(4-hydroxy-piperidin-l-yl)-ethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(2-(4-hydroxy-piperidin-l-yl) -ethyl-amino)-aniline Rf value: 0.3 (silica gel, methylene chloride/methanol = 5:1) ^-30^31^3^4 ESI mass spectrum: m/z = 496 [M-H"] (79) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-propylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(2-dimethylamino-ethyl)-N-propylsulphonyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C3oH34N405S ESI mass spectrum: m/z = 561 [M-H"] (80) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-butylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(2-dimethylamino-ethyl)-N butylsulphonyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C31H36N405S ESI mass spectrum: m/z = 575 [M-H-] (81) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-phenylsulphonyl-amino)-anilino)-1-pfrenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(2-dimethylamino-ethyl)-N phenylsulphonyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C33H32N405S ESI mass spectrum: m/z = 595 [M-H-] (82) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-benzylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(2-dimethylamino-ethyl)-N benzylsulphonyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C34H34N405S ESI mass spectrum: m/z = 609 [M-H"] (83) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-ethylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(2-dimethylamino-ethyl)-N ethylsulphonyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C-29^32^4®S® ESI mass spectrum: m/z = 547 [M-H"] (84) 3-Z-[1-(4-((imidazolidin-2,4-dion-5-yl)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((imidazolidin-2,4-dion-5-yl)-methyl)-aniline Rf value: 0.6 (silica gel, methylene chloride/methanol = 5:1) ^27^22^4^5 ESI mass spectrum: ft/z = 481 [M-H"] (85) 3-Z-[1-(4-((3-hydroxy-pyrrolidin-l-yl)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((3-hydroxy-pyrrolidin-l-yl) -methyl)-aniline Rf value: 0.1 (silica gel, methylene chloride/methanol = 10:1) ^•28^271^3(1)4 ESI mass spectrum: m/z = 468 [M-H-] (86) 3-Z-[1-(4-(cyclohexylyl-methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(cyclohexyl-methyl)-aniline (Eur. J. Med. Chem. Chim. Ther. 1992, 27, 537-544) Rf value: 0.6 (silica gel, methylene chloride/methanol = 10:1) *-30^30^2^3 ESI mass spectrum: m/z = 465 [M-H"] (87) 3-Z-[1-(4-(cyclohexyl-carbonyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(cyclohexyl-carbonyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 10:1) C"30^28^2®4 ESI mass spectrum: m/z = 479 [M-H"] (88) 3-Z-[1-(4-diethylaminomethyl-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(diethylamino-methyl)-aniline Rf value: 0.4 (silica gel, methylene chloride/methanol = 10:1) C28H29N303 ESI mass spectrum: iti/z = 454 [M-H"] (89) 3-Z-[1-(4-(N-(n-hexyl)-N-methyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(n-hexyl)-N-methyl-aminomethyl) -aniline Rf value: 0.6 (silica gel, methylene chloride/methanol = 10:1) C31H35N303 ESI mass spectrum: m/z = 496 [M-H"] (90) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-(furan-2-carbonyl)-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl)-N-(furan-2-carbonyl)-amino)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C32H30N4O5 ESI mass spectrum: m/z = 549 [M-H"] (91) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-(2-methoxy-benzoyl) -amino)-anilino)-1-phenyl-methylene]-6-methoxy-carbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl)-N-(2-methoxy-benzoyl)-amino)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c35h34n4o5 ESI mass spectrum: m/z = 589 [M-H-] (92) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-(pyridine-3-carbonyl)-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl) N-(pyridine-3-carbonyl)-amino)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c33h31n5o4 ESI mass spectrum: m/z = 560 [M-H"] (93) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-(phenyl-acetyl)-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl) N-(phenyl-acetyl)-amino)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c35h34n4o4 ESI mass spectrum: m/z = 573 [M-H"] (94) 3-Z-[1-(4-(N-ethyl-N-methyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-ethyl-N-methyl-aminomethyl)-aniline Rf value: 0.3 (silica gel, methylene chloride/methanol = 10:1) c27h27n3o3 ESI mass spectrum: m/z = 440 [M-H"] (95) 3-Z-[1-(4-(imidazol-2-yl)-anilino)-1-phenyl-methylene]-6 methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(imidazol-2-yl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 10:1! C26H20N4O3 ESI mass spectrum: m/z = 435 [M-H"] (96) 3-Z- [1-(4-(l-ethyl-imidazol-2-yl)-anilino)-1-phenyl-methylene] - 6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(l-ethyl-imidazol-2-yl)-aniline ' Rf value: 0.4 (silica gel, methylene chloride/methanol = 10:1) c28h24n403 esi mass spectrum: m/z = 463 [m-h"] (97) 3-Z- [1-(4-(l-benzyl-imidazol-2-yl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(l-benzyl-imidazol-2-yl)-aniline Rf value: 0.3 (silica gel, methylene chloride/methanol = 20:1) c33h26n4o3 esi mass spectrum: m/z = 525 [m-h"] (98) 3-Z- [1-(4-(N-(2-dimethylamino-ethyl)-N-isopropylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(2-dimethylamino-ethyl)-N-isopropylsulphonyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c30h34n4o5s esi mass spectrum: m/z = 561 [m-h"] (99) 3-Z- [1-(4-(N-(piperidin-l-yl-methylcarbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(piperidin-l-yl-methylcarbonyl )-N-methyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) ^"•31^32^4^4 ESI mass spectrum: m/z = 523 [M-H"3 (100) 3-Z-[1-(4-(N-(morpholin-4-yl-methylcarbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(morpholin-4-yl-methylcarbonyl)-N-methyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C30H30N4O5 ESI mass spectrum: m/z = 525 [M-H-] (101) 3-Z-[1-(4-(N-((4-benzyl-piperazin-l-yl)-methylcarbonyl) N-methyl-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-((4-benzyl-piperazin-l-yl) methylcarbonyl)-N-methyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C37H37N504 ESI mass spectrum: m/z = 614 [M-H"] (102) 3-Z-[1-(4-(N-(pyrrolidin-1-yl-methylcarbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(pyrrolidin-l-yl-methylcarbonyl)-N-methyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C-3oH3oN404 ESI mass spectrum: m/z = 509 [M-H"] (103) 3-Z- [1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-3-bromo-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-3-bromo-aniline Rf value: 0.6 (silica gel, methylene chloride/methanol = 5:1) ^-29^29®^-"^4^4 ' ESI mass spectrum: m/z = 575/577 [M-H"] (104) 3-Z-[1-(4-(5-methyl-imidazol-4-yl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(5-methyl-imidazol-4-yl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol/ammonia = 10:1:0.01) ^-•27^22^4^3 ESI mass spectrum: m/z = 449 [M-H-] (105) 3-Z-[1-(4-(N-((2-dimethylamino-ethyl)-carbonyl)-N-isopropyl-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-((2-dimethylamino-ethyl)-carbonyl)-N-isopropyl-p-phenylenediamine Rf value: 0.1 (silica gel, methylene chloride/methanol = 10:1) *-31^34^4^O4 ESI mass spectrum: m/z = 525 [M-H"] (106) 3-Z-[1-(4-(N-((2-dimethylamino-ethyl)-carbonyl)-N-benzyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-((2-dimethylamino-ethyl)-carbonyl)-N-benzyl-p-phenylenediamine Rf value: 0.1 (silica gel, methylene chloride/methanol = 10:1) c31h34n404 ESI mass spectrum: m/z = 525 [M-H"] (107) 3-Z-[1-(4-(N-butyl-N-tert.butoxycarbonyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-butyl-N- tert.butoxycarbonyl-aminomethyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c33h37n305 ESI mass spectrum: m/z = 554 [M-H-] (108) 3-Z-[1-(4-(N-((N-aminocarbonylmethyl-N-methyl-amino)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(N-aminocarbonylmethyl-N-methyl-amino)-methylcarbonyl)-N-methyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c29h29n5o5 ESI mass spectrum: m/z = 526 [M-H"] (109) 3-Z-[1-(4-(N-((N-benzyl-N-methyl-amino)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-((N-benzyl-N-methyl-amino)-methylcarbonyl)-N-methyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c34h32n404 ESI mass spectrum: m/z = 559 [M-H"] (110) 3-Z-[1-(4-(N-(di-(2-methoxyethyl)-amino-methylcarbonyl) N-methyl-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(di-(2-methoxyethyl)-amino methylcarbonyl)-N-methyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c32h36n406 ESI mass spectrum: m/z = 571 [M-H"] (111) 3-Z-[1-(4-(N-((2-(4-tert.butoxycarbonyl-piperazin-l-yl) ethyl)-carbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene] 6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-((2-(4-tert.butoxycarbonyl piperazin-l-yl)-ethyl)-carbonyl)-N-methyl-p-phenylenediamine Rf value: 0.8 (silica gel, methylene chloride/methanol = 5:1) c36h41n5o6 ESI mass spectrum: m/z = 638 [M-H"] (112) 3-Z-[1-(4-(N-((2-(piperidin-l-yl)-ethyl)-carbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-((2-(piperidin-l-yl)-ethyl)-carbonyl)-N-methyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 5:1) c32h34n404 ESI mass spectrum: m/z = 537 [M-H"] (113) 3-Z-[1-(4-(N-((2-(N-benzyl-N-methyl-amino)-ethyl)-carbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-((2-(N-benzyl-N-methyl-amino) -ethyl)-carbonyl)-N-methyl-p-phenylenediamine Rf value: 0.4 (silica gel, methylene chloride/methanol = 10:1) C35H34N404 ESI mass spectrum: m/z = 573 [M-H-] (114) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-isopropyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N- (dimethylaminomethylcarbonyl)-N-isopropyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C30H32N4O4 ESI mass spectrum: m/z = 511 [M-H"] (115) 3-Z-[1-(4-(N-(piperidin-l-yl-methylcarbonyl)-N-isopropyl-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(piperidin-l-yl-methylcarbonyl )-N-isopropyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c33h36n4o4 ESI mass spectrum: m/z = 551 [M-H"] (116) 3-Z-[1-(4-(n-((4-tert.butoxycarbonyl-piperazin-1-yl)-methylcarbonyl)-n-isopropyl-amino)-anilino)-1-phenyl-methylene ]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-((4-tert.butoxycarbonyl-piperazin-1-yl)-methylcarbonyl)-N-isopropyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C37H43N506 ESI mass spectrum: m/z = 652 [M-H"] (117) 3-Z-[1-(4-(N-((N-benzyl-N-methyl-amino)-methylcarbonyl) N-benzyl-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-((N-benzyl-N-methyl-amino) methylcarbonyl)-N-benzyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) ^•40-^36^4^4 ESI mass spectrum: m/z = 635 [M-H"] (118) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-benzyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and N-(dimethylaminomethylcarbonyl )-N-benzyl-p-phenylenediamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C34H32N404 ESI mass spectrum: m/z = 559 [M-H"] (119) 3-Z-[1-(4-(N-(piperidin-l-yl-methylcarbonyl)-N-benzyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(5-methyi-imidazol-4-yl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C37H36N404 ESI mass spectrum: m/z = 559 [M-H"] (120) 3-Z-[l-(4-(l,2,4-triazol-2-yl-methyl)-anilino)-1-phenyl methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(1,2,4-triazol-l-yl-methyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 10:1) c26h21n5o3 ESI mass spectrum: m/z = 450 [M-H"] (121) 3-Z-[1-(4-(1,2,3-triazol-2-yl-methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4 -(1,2,3-triazol-2-yl-methyl)-aniline Rf value: 0.5 (siliqa gel, methylene chloride/methanol = 20:1) ^"•26^21-^5^3 ESI mass spectrum: m/z = 450 [M-H"] (122) 3-Z-[1-(4-(1,2,3-triazol-1-yl-methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(1,2,3-triazol-1-yl-methyl)-aniline Rf value: 0.4 (silica gel, methylene chloride/methanol = 9:1) c26h21n5o3 ESI mass spectrum: m/z = 450 [M-H"] (123) 3-Z-[1-(4-((N-aminocarbonylmethyl-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((N-aminocarbonylmethyl-N-methyl-amino)-methyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c27h26n4o4 ESI mass spectrum: m/z = 469 [M-H"] (124) 3-Z-[1-(4-((di-(2-methoxy-ethyl)-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((di-(2-methoxy-ethyl)-amino)-methyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C30H33N3O5 ESI mass spectrum: m/z = 514 [M-H"] (125) 3-Z-[1-(4-(pyrrolidin-1-yl-methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(pyrrolidin-1-yl-methyl)-aniline , Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C28H27N303 ESI mass spectrum: m/z = 452 [M-H"] (126) 3-Z-[1-(4-((di-(2-hydroxy-ethyl)-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((di-(2-hydroxy-ethyl)-amino)-methyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C28H29N3Os ESI mass spectrum: m/z = 486 [M-H"] (127) 3-Z-[1-(4-((N-ethoxycarbonylmethyl-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((N-ethoxycarbonylmethyl-N methyl-amino)-methyl)-aniline Rf value: 0.5 (aluminium oxide, methylene chloride/ethanol = 40:1) ^--29^29^3^5 ESI mass spectrum: m/z = 498 [M-H"] (128) 3-Z-[1-(4-(azetidin-l-yl-methyl)-anilino)-1-phenyl-methylene ]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(azetidin-l-yl-methyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol/ammonia = 9:1:0.5) ^-27^25^3^3 ESI mass spectrum: m/z = 438 [M-H"] (129) 3-Z-[1-(4-(N-propyl-N-tert.butoxycarbonyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-propyl-N- tert.butoxycarbonyl-aminomethyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C32H35N305 ESI mass spectrum: m/z = 540 [M-H"] (130) 3-Z-[1-(4((N-(2-(2-methoxy-ethoxy)-ethyl)-N-methyl-amino) -methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl- 2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((N-(2-(2-methoxy-ethoxy)-ethyl)-N-methyl-amino)-methyl)-aniline Rf value: 0.4 (silica gel, methylene chloride/methanol = 9:1) ^--30^33^3^5 ESI mass spectrum: m/z = 514 [M-H"] (131) 3-Z-[1-(4-((N-(tert.butoxycarbonyl-3-amino-propyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxy-carbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(N-(N-tert.butoxycarbonyl- 3-amino-propyl)-N-methyl-aminomethyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C33H38N405 ESI mass spectrum: m/z = 571 [M+H+] (132) 3-Z-[1-(4-((N-(methylcarbamoyl-methyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((N-(methylcarbamoyl-methyl)-N-methyl-amino)-methyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) ^28^-28^4^4 , ESI mass spectrum: m/z = 483 [M-H"] (133) 3-Z-[1-(4-((N-(dimethylcarbamoyl-methyl)-N-methyl-amino) -methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl 2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((N-(dimethylcarbamoyl-methyl)-N-methyl-amino)-methyl)-aniline Rf value: 0.3 (silica gel, methylene chloride/methanol == 10:1) C29H30N4O4 ESI mass spectrum: m/z = 497 [M-H"] (134) 3-Z-[1-(4-methyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6- methoxycarbonyl-2-indolinone and 4-methyl-aniline Rf value: 0.4 (silica gel, methylene chloride/methanol = 9:1) ^--24^20^2^3 ESI mass spectrum: m/z = 383 [M-H"] (135) 3-Z-[1-(4-((N-propyl-N-methyl-amino)-methyl)-anilino)-1 phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((N-propyl-N-methyl-amino) methyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) ^~2 8^2 9^3 ^3 ESI mass spectrum: m/z = 454 [M-H"] (136) 3-Z-[1-(4-((N-(2-hydroxy-ethyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((N-(2-hydroxy-ethyl)-N-methyl-amino)-methyl)-aniline Rf value: 0.5 (aluminium oxide, methylene chloride/ethanol = 4 0:1) ^""2 7H2 7N3 ESI mass spectrum: m/z = 456 [M-H"] (137) 3-Z-[1-(4-((N-(2-dimethylamino-ethyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((N-(2-dimethylamino-ethyl) -N-methyl-amino)-methyl)-aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) ^•29^32^4^3 ESI mass spectrum: m/z = 483 [M-H"] (138) 3-Z- [1-(4-((N-(3-dimethylamino-propyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-((N-(3-dimethylamino-propyl) -N-methyl-amino)-methyl)-aniline aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C30H34N4O3 ESI mass spectrum: m/z = 497 [M-H"] (139) 3-Z- [1-(4-(3-oxo-piperazin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from l-acetyl-3-(1-ethoxy-l-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(3-oxo-piperazin-l-yl-methyl)-aniline aniline Rf value: 0.46 (silica gel, methylene chloride/methanol = 9:1) C28H26N404 ESI mass spectrum: m/z = 481 [M-H-] Example 4 , 3-Z-[1-(4-carboxy-anilino)-1-phenyl-methylene]-6-ethoxy- carbonvl-2 -indolinone 485 mg of 3-Z-[1-(4-tert.butoxycarbonyl-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone are dissolved in 15 ml of methylene chloride and 6.0 ml of trifluoroacetic acid are added. The mixture is stirred for 2 hours at room temperature. Then the solvent is removed and the residue recrystallised from ether.

Yield: 375 mg (87 % of theory), Rf value: 0.3 (silica gel, methylene chloride/methanol = 10:1) ^--25^-2 0^2^5 Mass spectrum: m/z = 428 [M+] The following compounds are prepared analogously to Example 4 : (1) 3-Z-[1-(4-aminomethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-(N-tert.butoxycarbonyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Rf value: 0.5 (silica gel, methylene chloride/methanol/ammonia = 5:1:0.01) ^-24^-21^3^3 ESI mass spectrum: m/z = 398 [M-H"] (2) 3-Z-[1-(4-ethylaminomethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from 3-Z-[1-(4-(N-tert.butoxycarbonyl-ethylamino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Rf value: 0.4 (silica gel, methylene chloride/methanol/ammonia = 10:1:0.01) *"-"26^-25^303 ESI mass spectrum: m/z = 426 [M-H"] (3) 3-Z- [1-(4-carboxymethyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone Prepared from 3-Z-[1-(4-tert.butoxycarbonylmethyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Rf value: 0.1 (aluminium oxide, methylene chloride/ethanol/ammonia = 5:1:0.01) ^""26^22^2^5 ESI mass spectrum: m/z = 441 [M-H"] (4) 3-Z- [1-(4-carboxy-anilino)-1-ethyl-methylene]-6-ethoxy-carbonyl-2 -indolinone Prepared from 3-Z-[1-(4-tert.butoxycarbonyl-anilino)-1-ethyl-methylene] -6-ethoxycarbonyl-2-indolinone Rf value: 0.1 (aluminium oxide, methylene chloride/ethanol = 20:1) '"21^20^2^5 ESI mass spectrum: m/z = 379 [M-H"] (5) 3-Z- [1-(4-(piperazin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-(4-tert.butoxycarbonyl-piperazin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Rf value: 0.1 (silica gel, methylene chloride/methanol/ammonia = 10:1:0.01) *-"28^28^4^3 ESI mass spectrum: m/z = 469 [M+H+] (6) 3-Z-[1-(4-butylaminomethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from 3-Z- [1-(4-(N-butyl-N-tert.butoxycarbonyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) C28H29N303 ESI mass spectrum: m/z = 454 [M-H"] i (7) 3-Z-[1-(4-ethylaminomethyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone Prepared from 3-Z-[1-(4-(N-tert.butoxycarbonyl-N-ethyl-aminomethyl) -anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Rf value: 0.3 (silica gel, methylene chloride/methanol/ammonia = 10:1:0.01) ^—27*^27^3^3 ESI mass spectrum: m/z = 442 [M+H+] (8) 3-Z-[1-(4-ethylaminomethyl-anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone Prepared from 3-Z-[1-(4-(N-tert.butoxycarbonyl-ethylaminomethyl) -anilino)-1-phenyl-methylene] -6-carbamoyl-2-indolinone Rf value: 0.2 (silica gel, methylene chloride/methanol/ammonia = 5:1:0.01) c25h24n4o2 ESI mass spectrum: m/z = 411 [M-H"] (9) 3-Z-[1-(4-(N-(piperazin-1-yl-methylcarbonyl)-N-isopropyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-(N-((4-tert.butoxycarbonyl-piperazin-1-yl)-methylcarbonyl)-N-isopropyl-amino)-anilino)-1-phenyl-me t hy1ene]-6-methoxycarbony1-2-indo1inone Rf value: 0.35 (silica gel, methylene chloride/methanol = 9:1) c32h35n5o4 ESI mass spectrum: m/z = 552 [M-H-] (10) 3-Z-[1-(4-(N-((2-(piperazin-l-yl)-ethyl)-carbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from 3-Z-[1-(4-(N-((2-(4-tert.butoxycarbonyl-piperazin-l-yl)-ethyl)-carbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Rf value: 0.4 (silica gel, methylene chloride/methanol/ammonia = 5:1:0.01) c31h33n5o4 ESI mass spectrum: m/z = 54 0 [M+H+] (11) 3-Z-[1-(4-(N-propyl-aminomethyl) -anilino)-1-phenyl-methylene ]-6-methoxycarbonyl-2 -indolinone Prepared from 3-Z-[1-(4-(N-propyl-N-tert.butoxycarbonyl-aminomethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Rf value: 0.35 (silica gel, methylene chloride/methanol = 9:1) C27H27N3O3 ESI mass spectrum: m/z = 440 [M-H"] (12) 3-Z-[1-(4-((N-(3-amino-propyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-((N-(tert.butoxycarbonyl-3-amino-propyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Rf value: 0.35 (silica gel, methylene chloride/methanol = 9:1) C2 8^3 0^4® 3 ESI mass spectrum: m/z = 471 [M+H+] Example 5 3-Z-[1-(4-methylaminomethyl-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone 100 mg of 3-Z-[1-(4-(N-benzyl-N-methyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone are dissolved in 2 0 ml of ethanol, 0.2 ml of IN hydrochloric acid are added and the mixture is hydrogenated for 70 minutes at room temperature ancl 50 psi hydrogen pressure. The reaction solution is filtered and the filtrate concentrated by rotary evaporation. The residue is dried in vacuo at 100°C.

Yield: 50 mg (53 % of theory), Rf value: 0.3 (silica gel, methylene chloride/ethanol/ammonia = 5:1:0.01) C26H25N3O3 ESI mass spectrum: m/z = 426 [M-H"] The following compounds are prepared analogously to Example 5: (1) 3-Z-[1-(4-methylaminomethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from 3-Z-[1-(4-(N-benzyl-N-methyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Rf value: 0.2 (silica gel, methylene chloride/methanol/ammonia = 10:1:0.01) ^-■25^23^3^3 ESI mass spectrum: m/z = 412 [M-H"] (2) 3-Z-[1-(4-(N-(2-methylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-((2-(N-benzyl-N-methyl-amino)-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Rf value: 0.3 (silica gel, methylene chloride/methanol/ammonia = 10:1:0.01) C27H28N405S ESI mass spectrum: m/z = 519 [M-H"] (3) 3-Z-[1-(4-(N-(2-amino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-(N-cyanomethyl-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Rf value: 0.5 (silica gel, methylene chloride/methanol/ammonia = 5:1:0.01) C26H26N405S ESI mass spectrum: m/z = 505 [M-H"] (4) 3-Z-[1-(4-(N-(3-methylamino-propyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-(N-(3-(N-benzyl-N-methyl-amino)-propyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Rf value: 0.3 (silica gel, methylene chloride/methanol/ammonia = 5:1:0.01) C28H30N4O5S ESI mass spectrum: m/z = 533 [M-H"] (5) 3-Z-[1-(4-(N-(piperazin-1-yl-methylcarbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-(N-((4-benzyl-piperazin-l-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Rf value: 0.5 (silica gel, methylene chloride/methanol = 9:1) c30h31n5o4 ESI mass spectrum: m/z = 524 [M-H"] (6) 3-Z- [1- (4-(N-(methylamino-raethylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4 -(N-((N-benzyl-N-methyl-amino)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]- 6-methoxycarbonyl-2-indolinone Rf value: 0.3 (silica gel, methylene chloride/methanol = 9:1) ^-■27^26^4^4 ESI mass spectrum: m/z = 469 [M-H"] I (7) 3-Z-[1-(4-(N-((2-methylamino-ethyl)-carbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-(N-((2-(N-benzyl-N-methyl-amino)-ethyl)-carbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Rf value: 0.3 (silica gel, methylene chloride/methanol/ammonia = 5:1:0.01) ^-28^28^4®4 ESI mass spectrum: m/z = 483 [M-H"] Example 6 3-Z-[1-(4-ureidomethyl-anilino)-1-phenyl-methylene]-6-methoxy- carbonvl-2-indolinone 300 mg of 3-Z-[1-(4-aminomethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone are dissolved in 15 ml of methanol and 200 ml of triethylamine are added. Then 400 mg of potassium cyanate in 5 ml of water are added. After 2 days of stirring at room temperature the reaction solution is concentrated by rotary evaporation, the residue taken up in methylene chloride and washed once with water and once with saturated sodium chloride solution. The organic phase is dried over sodium sulphate and concentrated by rotary evaporation. The residue is dried in vacuo at 100°C.

Yield: 100 mg of (21 % of theory), Rf value: 0.7 (silica gel, methylene chloride/methanol = 5:1) c25h22n4o4 ESI mass spectrum: m/z = 441 [M-H"] Example 7 3-Z-[1-(4-guanidinomethyl-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone 300 mg of 3-Z-[1-(4-aminomethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone are dissolved in 5 ml of dimethylformamide and 3 00 ml of triethylamine are added. Then 700 mg of 3,5-dimethylpyrazol-l-carboxylic acid amidine in 5 ml of dimethylformamide are added. After one day of stirring at room temperature the reaction solution is concentrated by rotary evaporation. The residue is dried at 100°C in vacuo.

Yield: 200 mg (87 % of theory), Rf value: 0.1 (Reversed phase RP 8, methanol/five percent saline solution = 6:4) c25h23n503 Mass spectrum: m/z = 441 [M+] Example 8 3-Z-[1-(4-acetylaminomethyl-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone 100 mg of 3-Z-[1-(4-aminomethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone are dissolved in 5 ml of glacial acetic acid, 0.1 ml of acetic anhydride is added and the mixture is stirred for 10 minutes at room temperature. After this time the reaction solution is poured onto saturated soda solution and extracted four times with methylene chloride. The combined organic phases are washed with saturated saline solution, dried over sodium sulphate and concentrated by rotary evaporation. The residue is dried at 100°C in vacuo.

Yield: 20 mg (23 % of theory), Rf value: 0.4 (silica gel, methylene chloride/methanol = 10:1) *"•26^23^3^4 ESI mass spectrum: m/z = 440 [M-H"} The following compounds are prepared analogously to Example 8: (1) 3-Z-[1-(4-(N-methylsulphonyl-aminomethyl)-anilino)-1- I phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from 3-Z-[1-(4-aminomethyl-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone and methanesulphonyl chloride/triethylamine Rf value: 0.7 (silica gel, methylene chloride/methanol = 5:1) '-'25^23^3^IS® ESI mass spectrum: m/z = 476 [M-H"] (2) 3-Z-[1-(4-(4-benzoyl-piperazin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Prepared from 3-Z-[1-(4-(piperazin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone and benzoyl chloride Rf value: 0.7 (silica gel, methylene chloride/methanol = 10:1) C35H32N404 ESI mass spectrum: m/z = 571 [M-H"] (3) 3-Z-[1-(4-((N-(3-acetylamino-propyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-((N-(3-amino-propyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Rf value: 0.3 (silica gel, methylene chloride/methanol = 9:1) *-30-^32^4^4 ESI mass spectrum: m/z = 511 [M-H"] Example 9 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl- methvlenel- 6-carboxy-2-indolinone 0.8 g of 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone are dissolved in 30 ml of ethanol, 8.3 ml of IN sodium hydroxide solution are added and the mixture is stirred for 1 hour at 80°C. After cooling, it is neutralised with 8.3 ml of IN hydrochloric acid. The precipitate formed is suction filtered, washed with water, ethanol and ether and dried in vacuo at 100°C.

Yield: 0.7 g of (89 % of theory), Rf value: 0.2 (silica gel, methylene chloride/methanol = 5:2) C28H27N303 Mass spectrum: m/z = 453 [M+] The following compounds are prepared analogously to Example 9: (1) 3-Z-[1-(4-bromo-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone Prepared from 3-Z-[1-(4-bromo-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Rf value: 0.4 (silica gel, toluene/ethyl acetate = 5:1) C22H15BrN203 ESI mass spectrum: m/z = 435/437 [M+H+] (2) 3-Z-[1-(3-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-carboxy-2-indolinone Prepared from 3-Z-[1-(3-(dimethylaminomethyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone Rf value: 0.7 (Reversed phase RP 8, methanol/five percent saline solution = 4:1) C25H23N303 ESI mass spectrum: m/z = 414 [M+H+] (3) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene ]-6-carboxy-2 -indolinone Prepared from 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone Rf value: 0.7 (Reversed phase RP 8, methanol/five percent saline solution = 4:1) C25H23N303 ESI mass spectrum: m/z = 412 [M-H"] (4) 3-Z-[1-(4-[(2,6-dimethyl-piperidin-1-yl)-methyl]-anilino)-1-phenyl-methylene]-6 -carboxy-2 -indolinone Prepared from 3-Z-[1-(4-[ (2,6-dimethyl-piperidin-1-yl)-methyl]-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone Rf value: 0.6 (Reversed phase RP 8, methanol/five percent saline solution = 4:1) C30H31N3O3 ESI mass spectrum: m/z = 482 [M+H+] (5) 3-Z-[1-(4-(l-methyl-imidazol-2-yl)-anilino)-1-phenyl-methylene ]-6-carboxy-2 -indolinone Prepared from 3-Z-[1-(4-(1-methyl-imidazol-2-yl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone Rf value: 0.6 (Reversed phase RP 8, methanol/five percent saline solution = 4:1) c26h20n4o3 ESI mass spectrum: m/z = 435 [M-H"] (6) 3-Z-[1-(4-(N-acetyl-N-dimethylaminocarbonylmethyl-amino)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone Prepared from 3-Z-[1-(4-(N-acetyl-N- dimethylaminocarbonylmethyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone Rf value: 0.3 (silica gel, methylene chloride/methanol = 10:1) C28H26N4Os ESI mass spectrum: m/z = 497 [M-H"] (7) 3-Z-[1-(4-ethylaminomethyl-anilino)-1-phenyl-methylene]-6-carboxy-2 -indolinone Prepared from 3-Z-[1-(4-ethylaminomethyl-anilino)-1-phenyl- methylene] - 6-methoxycarbonyl-2-indolinone Rf value: 0.6 (Reversed phase RP 8, methanol/five percent saline solution = 4:1) C2SH23N303 ESI mass spectrum: m/z = 412 [M-H"] (8) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone Prepared from 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Rf value: 0.6 (Reversed phase RP 8, methanol/five percent saline solution = 4:1) C27H26N404 ESI mass spectrum: m/z = 469 [M-H"] (9) 3-Z-[1-(4-(N-tert.butoxycarbonyl-ethylaminomethyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone Prepared from 3-Z-[1-(4-(N-tert.butoxycarbonyl-ethylaminomethyl) -anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone Rf value: 0.4 (silica gel, methylene chloride/methanol = 10:1) C3oH31N305 ESI mass spectrum: m/z = 512 [M-H"] (10) 3-Z-[1-(4-((N-carboxymethyl-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-((N-ethoxycarbonylmethyl-N-methyl-amino) -methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl -2 -indolinone R£ value: 0.4 (silica gel, methylene chloride/methanol = 6:1) c27h2sn3o5 ESI mass spectrum: m/z = 470 [M-H"] Example 10 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl- methvlenel-6-methoxycarbonyl-2-indolinone 0.9 g of 3-Z-[1-(4-.'(piperidin-1-yl-methyl)-anilino)-1-phenyl-methylene] -6-carboxy-2-indolinone are suspended in 35 ml of dimethylformamide and 0.4 g of carbonyldiimidazole are added. The mixture is stirred for 14 hours at 80°c. After this time 20 ml of methanol are added and the mixture is stirred for another 3 hours at 50°c. The solvent is removed and the residue is purified over a silica gel column with methylene chloride/methanol (3:1) as eluant.

Yield: 0.5 g of (49% of theory), Rf value: 0.5 (aluminium oxide, methylene chloride/methanol = 30:1) *--29^29^3^3 ESI mass spectrum: m/z = 468 [M+H+] The following compounds are prepared analogously to Example 10 : (1) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-benzyloxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and benzyl alcohol Rf value: 0.6 (aluminium oxide, methylene chloride/methanol = 30:1) C35H33N303 Mass spectrum: m/z = 543 [M+] (2) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-isopropyloxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and isopropanol Rf value: 0.4 (aluminium oxide, methylene chloride/isopropanol = 30:1) C31H33N3O3 Mass spectrum: m/z = 4 95 [M+] (3) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-propyloxycarbonyl-2-indolinone Prepared from 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and n-propanol Rf value: 0.7 (silica gel, methylene chloride/methanol = 5:1) C31H33N303 Mass spectrum: m/z = 495 [M+] (4) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-butyloxycarbonyl-2 -indolinone Prepared from 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)- 1-phenyl-methylene]-6-carboxy-2-indolinone and n-butanol Rf value: 0.5 (silica gel, methylene chloride/methanol = 10:1) C32H35N3O3 Mass spectrum: m/z = 509 [M+] (5) 3-Z-[1-(4-bromo-anilino)-1-phenyl-methylene]-6-carbamoyl- 2-indolinone Prepared from 3-Z-[1-(4-bromo-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and ammonia Rf value: 0.5 (silica gel, methylene chloride/methanol = 10:1) C22HlsBrN203 Mass spectrum: m/z = 432/434 [M-H"] (6) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-ethylcarbamoyl-2 -indolinone Prepared from 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and ethylamine gas Rf value: 0.6 (silica gel, methylene chloride/methanol = 5:1) C30H32N4O2 Mass spectrum: m/z = 480 [M+] (7) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-[(2-methoxy-ethoxy)-carbonyl]-2-indolinone Prepared from 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and methylglycol Rf value: 0.8 (silica gel, methylene chloride/methanol = 4:1) ^-*25^23^3^3 ESI mass spectrum: m/z = 470 [M-H"] (8) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-[(2-dimethylamino-ethoxy)-carbonyl]-2-indolinone Prepared from 3-Z-[1-(4-(dimethylaminomethyl)-anilino)- 1-phenyl-methylene]-6-carboxy-2-indolinone and 2-dimethylaminoethanol aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 5:2) C29H32N403 ESI mass spectrum: m/z = 483 [M-H"] (9) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-[(2-N-tert.butoxycarbonyl-amino-ethoxy)-carbonyl]-2-indolinone Prepared from 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and 2-N-tert.butoxycarbonyl-amino-ethanol aniline Rf value: 0.8 (silica gel, methylene chloride/methanol = 5:2) C32H36N405 ESI mass spectrum: m/z = 412 [M-H"] (10) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-[(2,2,2-trifluoroethoxy)-carbonyl]-2-indolinone Prepared from 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and 2,2,2-trifluoroethanol aniline Rf value: 0.5 (silica gel, methylene chloride/methanol = 5:1) c27h24f3n3o3 ESI mass spectrum: m/z = 494 [M-H"] Example 11 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl- methvlene1 -6 -carbamoyl-2 -indolinone 0.9 g of 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-carboxy-2-indolinone, 0.8 g of TBTU and 0.4 g of HOBT are suspended in 25 ml of dimethylformamide and 1.0 ml of triethylamine are added. The mixture is stirred for 15 minutes at room temperature. After this time ammonia gas is introduced at 10-15°C over a period of 15 minutes and the mixture is stirred for 1.5 hours at room temperature. The precipitate formed is suction filtered, washed with water, ethanol and ether and dried at 100°C in vacuo.

Yield: 0.6 g (64 % of theory), Rf value: 0.4 (Reversed phase RP 8, methanol/five percent saline solution = 6:4) ^•28^28^402 ESI mass spectrum: m/z = 453 [M+H+] The following compounds are prepared analogously to Example 11 : (1) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-dimethylcarbamoyl-2-indolinone Prepared from 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and dimethylamine hydrochloride/diisopropylethylamine Rf value: 0.5 (silica gel, methylene chloride/methanol = 5:! ^-30^32^4^2 ESI mass spectrum: m/z = 481 [M+H+] (2) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-(N-ethyl-N-methyl-carbamoyl)-2-indolinone Prepared from 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and N-ethyl-N-methyl-amine Rf value: 0.5 (aluminium oxide, methylene chloride/ethanol = 20:1) c31h34n4o2 ESI mass spectrum: m/z = 495 [M+H+] (3) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-me t hy1ene]-6 -me thy1carbamoy1-2-indolinone Prepared from 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and methylamine hydrochloride/diisopropylethylamine Rf value: 0.3 (aluminium oxide, methylene chloride/ethanol = 20 :1) ^2 ESI mass spectrum: m/z = 467 [M+H+] (4) 3-Z-[1-(3-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-methylcarbamoyl-2-indolinone Prepared from 3-Z-[1-(3-(dimethylaminomethyl)-anilino)-1-phenyl-methylene]-6-carboxyl-2-indolinone and methylamine hydrochloride/triethylamine Rf value: 0.3 (silica gel, methylene chloride/ethanol = 2:1) c26h26n4o2 Mass spectrum: m/z = 426 [M+] (5) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-(2-hydroxyethyl-carbamoyl)-2-indolinone Prepared from 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and ethanolamine/diisopropylethylamine Rf value: 0.5 (aluminium oxide, methylene chloride/methanol = :1) C30H32N4O3 ESI mass spectrum: m/z = 495 [M-H"] (6) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-diethylcarbamoyl-2 -indolinone Prepared from 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone and diethylamine hydrochloride/diisopropylethylamine Rf value: 0.8 (aluminium oxide, methylene chloride/methanol = :1) C32H36N402 ESI mass spectrum: m/z = 509 [M+H+] (7) 3-Z-[1-(4-(N-tert.butoxycarbonyl-ethylaminomethyl)-anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone Prepared from 3-Z-[1-(4 -(N-tert.butoxycarbonyl-ethylaminomethyl)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone Rf value: 0.3 (silica gel, toluene/ethyl acetate/ethanol = 4:2:1) C3oH32N404 ESI mass spectrum: m/z = 511 [M-H"] (8) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone Prepared from 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-carboxy-2-indolinone Rf value: 0.5 (silica gel, methylene chloride/methanol/ammonia ^-27-^27^5^3 ESI mass spectrum: m/z = 468 [M-H"] Example 12 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone x citric acid 3.25 g of citric acid monohydrate are placed in 50 ml of methanol and 5.0 g of 3-Z-[1-(4-(N-dimethylaminomethyl-carbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone are added at room temperature. The solution formed is evaporated down, the residue is washed with ether and recrystallised from ethyl acetate.

Yield: 6.3 g (90 % of theory), Rf value: 0.6 (silica gel, methylene chloride/methanol/ammonia = 5:1:0.01) Melting point: 198°C *"-28-^-28^405 x C6H807 ESI mass spectrum: m/z = 483 [M-H"] Elemental analysis: calc.: C 60.34 H 5.37 N 8.28 found: 59.98 5.25 8.13 The following compound is prepared analogously to Example 12: (1) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone x methanesulphonic acid Prepared from 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone and methanesulphonic acid Rf value: 0.6 (silica gel, methylene chloride/methanol/ammonia = 5:1:0.01) Melting point: 275°C C26H25N303 x CH403S ESI mass spectrum: m/z = 426 [M-H"] Elemental analysis: calc.: C 61.92 H 5.59 N 8.03 S 6.12 found: 61.43 5.87 7.85 5.39 The following compounds may be prepared analogously to the foregoing Examples: (1) 3-Z-(1-anilino-l-phenyl-methylene)- 6-ethoxycarbonyl-2-indolinone l (2) 3-Z-[1-(4-nitro-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (3) 3-Z- [1-(4-fluoro-anilino)-1-phenyl-methylene]-6-ethoxy carbonyl-2 -indolinone (4) 3-Z-[1-(4-chloro-anilino)-1-phenyl-methylene]-6-ethoxy carbonyl-2 -indolinone (5) 3-Z-[1-(4-iodo-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (6) 3-Z- [1-(4-cyano-anilino)-1-phenyl-methylene]-6-ethoxy-carbony1-2-indolinone (7) 3-Z-[1-(4-methoxy-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (8) 3-Z-[1-(4-ethoxy-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (9) 3-Z-[1-(4-trifluoromethyl-anilino)-1-phenyl-methylene] 6-ethoxycarbonyl-2 -indolinone (10) 3-Z-[1-(4-methyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (11) 3-Z-[1-(4-methylmercapto-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (12) 3-Z-[1-(4-aminomethyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (13) 3-Z-[1-(4-(isopropylaminomethyl)-anilino)-1-phenyl- methylene] -6-ethoxycarbonyl-2 -indolinone / (14) 3-Z-[1-(4-(anilinomethyl)-anilino)-1-phenyl-methylene]-6 -ethoxycarbonyl-2-indolinone (15) 3-Z-[1-(4-(propylaminomethyl)-anilino)-1-phenyl-methylene] -6 -ethoxycarbonyl-2-indolinone (16) 3-Z-[1-(4-(butylaminomethyl)-anilino)-1-phenyl-methylene] -6 -ethoxycarbonyl-2 -indolinone (17) 3-Z-[1-(4-(isobutylaminomethyl)-anilino)-1-phenyl-methylene] -6 -ethoxycarbonyl-2-indolinone (18) 3-Z-[1-(4-(cyclohexylaminomethyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (19) 3-Z-[1-(4-(benzylaminomethyl)-anilino)-1-phenyl-methy1ene]-6-ethoxycarbonyl-2 -indolinone (20) 3-Z-[1-(4-((N-ethyl-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (21) 3-Z-[1-(4-((N-methyl-N-propyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (22) 3-Z-[1-(4-((N-isopropyl-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (23) 3-Z- [1-(4-((N-ethyl-N-propyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (24) 3-Z-[1-(4-((N-ethyl-N-isopropyl-amino)-methyl)-anilino) 1-phenyl-methylene]- 6 -ethoxycarbonyl-2 -indolinone (25) 3-Z-[1-(4-(dipropylaminomethyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone t (26) 3-Z- [1-(4-(diisopropylaminomethyl)-anilino)-1-phenyl-methylene ]-6-ethoxycarbonyl-2-indolinone (27) 3-Z-[1-(4-((N-benzyl-N-ethyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (28) 3-Z-[1-(4-(dibenzylaminomethyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (29) 3-Z-[1-(4-(3,6-dihydro-2H-pyridin-1-yl-methyl)-anilino) 1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (30) 3-Z- [1-(4-(3,5-dimethyl-piperidin-l-yl-methyl)-anilino) 1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (31) 3-Z-[1-(4-(azepan-1-yl-methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (32) 3-Z-[1-(4-(piperazin-1-yl-methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (33) 3-Z-[1-(4-(morpholin-4-yl-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (34) 3-Z- [1-(4-(thiomorpholin-4-yl-methyl)-anilino)-1-phenyl methylene]-6-ethoxycarbonyl-2 -indolinone (35) 3-Z-[1-(4-(l-oxo-thiomorpholin-4-yl-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (36) 3-Z- [1-(4-(1,1-dioxo-thiomorpholin-4-yl-methyl)-anilino 1-phenyl-methylene]-6 -ethoxycarbonyl-2 -indolinone (37) 3-Z-[1-(4-(acetylamino-methyl)-anilino)-1-phenyl-methylene ]-6-ethoxycarbonyl- 2-indolinone (38) 3-Z-[1-(4-(2-amino-ethyl)-anilino)-1-phenyl-methylene]-6 - e thoxycarbonyl - 2 - indo 1 inone (39) 3-Z-[1-(4-(2-methylamino-ethyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (40) 3-Z-[1-(4-(2-ethylamino-ethyl)-anilino)-1-phenyl-methylene ]-6-ethoxycarbonyl-2 -indolinone (41) 3-Z-[1-(4-(2-diethylamino-ethyl)-anilino)-1-phenyl-methylene ] -6-ethoxycarbonyl-2 -indolinone (42) 3-Z-[1-(4-(2-piperidin-l-yl-ethyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (43) 3-Z-[1-(4-(2-acetylamino-ethyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (44) 3-Z-[1-(4-(3-amino-propyl)-anilino)-1-phenyl-methylene] 6-ethoxycarbonyl-2-indolinone (45) 3-Z-[1-(4-(3-dimethylamino-propyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (46) 3-Z-[1-(4-(N-aminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (47) 3-Z-[1-(4-(N-methylaminomethylcarbonyl-N-methyl-amino) anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (48) 3-Z-[1-(4-(N-ethylaminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (49) 3-Z-[1-(4-(N-diethylaminomethylcarbonyl-N-methyl-amino anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone / (50) 3-Z-[1-(4-(N-(piperidin-l-yl-methylcarbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (51) 3-Z-[1-(4-(N-(morpholin-4-yl-methylcarbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (52) 3-Z-[1-(4-(N-(piperazin-l-yl-methylcarbonyl)-N-methyl-amino] -anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (53) 3-Z-[1-(4-(N-(2-amino-ethylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (54) 3-Z-[1-(4-(N-(2-methylamino-ethylcarbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (55) 3-Z-[1-(4-(N-(2-diethylamino-ethylcarbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (56) 3-Z-[1-(4-(N-acetyl-N-(2-aminoethyl)-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (57) 3-Z-[1-(4-(N-acetyl-N-(2-methylamino-ethyl)-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (58) 3-Z-[1-(4-(N-acetyl-N-(2-methylamino-propyl)-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (59) 3-Z-[1-(4-(N-acetyl-N-(2-piperidin-l-yl-ethyl)-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (60) 3-Z-[1-(4-(N-acetyl-N-(aminocarbonylmethyl)-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (61) 3-Z-[1-(4-(N-acetyl-N-(dimethylaminocarbonylmethyl)-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (62) 3-Z-[1-(4-(N-acetyl-N-(piperidin-1-yl-carbonylmethyl)-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (63) 3-Z-[1-(4-(N-methyl-N-(aminocarbonyl)-amino)-anilino)-1-phenyl-methylene]-6 -ethoxycarbonyl-2-indolinone (64) 3-Z-[1-(4-(N-methyl-N-(methylaminocarbonyl)-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (65) 3-Z-[1-(4-(N-methyl-N-(dimethylaminocarbonyl)-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (66) 3-Z-[1-(4-(N-methyl-N-(piperidin-l-yl-carbonyl)-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (67) 3-Z-[1-(4-(N-(2-aminoethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (68) 3-Z-[1-(4-(N-(2-methylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (69) 3-Z-[1-(4-(N-(2-ethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (70) 3-Z- [1- (4- (N- (i>-diethylamino-ethyl) -N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (71) 3-Z-[1-(4-(N-(2-pyrrolidin-l-yl-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2- indolinone (72) 3-Z-[1-(4-(N-(2-piperidin-l-yl-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (73) 3-Z-[1-(4-(N-(2-piperazin-l-yl-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (74) 3-Z-[1-(4-(N-(2-(morpholin-4-yl)-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (75) 3-Z-[1-(4-(N-(aminocarbonylmethyl)-N-methylsulphonyl-amino) -anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (76) 3-Z-[1-(4-(N-(methylaminocarbonylmethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (77) 3-Z- [1- (4- (N- (ethylaminocarbonylmethyl) -time thyl sulphonyl-amino) -anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (78) 3-Z-[1-(4-(N-(N-(2-dimethylamino-ethyl)-N-methyl-amino) carbonylmethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene ]-6 -ethoxycarbonyl-2 -indolinone (79) 3-Z- [1- (4- (N- (cliethylaminocarbonylmethyl) -N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (80) 3-Z-[1-(4-(N-(pyrrolidin-l-yl-carbonylmethyl)-N-methylsulphonyl -amino) -anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (81) 3-Z-[1-(4-(N-(piperidin-1-yl-carbonylmethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (82) 3-Z-[1-(4-(N-(piperazin-l-yl-carbonylmethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (83) 3-Z-[1-(4-(N-((morpholin-4-yl)-carbonylmethyl)-N-methyl sulphonyl-amino)-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (84) 3-Z-[1-(4-(2-dimethylamino-ethoxy)-anilino)-1-phenyl-methylene] -6 -ethoxycarbonyl-2 -indolinone (85) 3-Z-[1-(4-(3-dimethylamino-propoxy)-anilino)-1-phenyl-methylene ]-6-ethoxycarbonyl-2 -indolinone (86) 3-Z-[1-(4-(aminocarbonylmethyl)-anilino)-1-phenyl-methylene] -6 -ethoxycarbonyl-2 -indolinone (87) 3-Z-[1-(4-(2-aminocarbonyl-ethyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (88) 3-Z-[1-(4-(pyridin-2-yl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (89) 3-Z-[1-(4-(pyridine-3-yl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (90) 3-Z-[1-(4-(pyridin-4-yl)-anilino)-1-phenyl-methylene]-6 -e t hoxycarbonyl-2 -indo1inone (91) 3-Z-[1-(4-(N-acetyl-N-methyl-amino)-anilino)-1-phenyl-methylene ]-6-ethoxycarbonyl-2 -indolinone (92) 3-Z-[1-(4-(N-ethylcarbonyl-N-(dimethylaminocarbonylmethyl) -amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl 2-indolinone (93) 3-Z-[1-(carbamoylmethyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (94) 3-Z-[1-(4-dimethylcarbamoylmethyl-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (95) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-methylene]-6-ethoxycarbony1-2-indo1inone (96) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-propylidene] 6 -ethoxycarbonyl-2-indolinone (97) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-butylidene]-6 -ethoxycarbonyl-2 -indolinone (98) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-anilino)-methylene]-6-ethoxycarbonyl-2-indolinone (99) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-anilino)-ethylidene]-6-ethoxycarbonyl-2-indolinone (100) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-anilino)-propylidene]-6-ethoxycarbonyl-2-indolinone (101) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-anilino)-butylidene]-6-ethoxycarbonyl-2-indolinone (102) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl amino)-anilino)-methylene]-6-ethoxycarbonyl-2-indolinone (103) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl amino)-anilino)-propylidene]-6-ethoxycarbonyl-2-indolinone (104) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl amino)-anilino)-butylidene]-6-ethoxycarbonyl-2-indolinone (105) 3-Z-[1-(4-tetrazol-5-yl-anilino)-methylene]-6-ethoxycarbonyl-2-indolinone (106) 3-Z-[1-(4-tetrazol-5-yl-anilino)-ethylidene]-6-ethoxy-carbonyl-2 -indolinone (107) 3-Z-[1-(4-tetrazol-5-yl-anilino)-propylidene]-6-ethoxy carbonyl-2-indolinone (108) 3-Z-[1-(4-tetrazol-5-yl-anilino)-butylidene]-6-ethoxycarbonyl-2 -indolinone (109) 3-Z-[1-(4-carboxy-anilino)-methylene] -6-ethoxycarbonyl 2-indolinone (110) 3-Z-[l-(4-carboxy-anilino)-propylidene]-6-ethoxycarbonyl- 2 -indolinone (111) 3-Z-[1-(4-carboxy-anilino)-butylidene]-6-ethoxycarbonyl-2-indolinone (112) 3-Z-[1-(4-(N-(3-dimethylamino-propionyl)-N-dimethylaminocarbonylmethyl-amino)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (113) 3-Z-[1-(4-(N-(4-dimethylamino-butyryl)-N-dimethylaminocarbonylmethyl-amino)-anilino)-1-phenyl-methylene ]-6-ethoxycarbonyl-2-indolinone (114) 3-Z-[1-(4-(N-dimethylaminocarbonylmethyl-N-(2-dimethylamino-ethylsulphonyl)-amino)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (115) 3-Z-[1-(4-(N-dimethylaminocarbonylmethyl-N-(3-dimethylamino-propylsulphonyl)-amino)-anilino)-1-phenyl-methylene ] -6-ethoxycarbonyl-2 -indolinone (116) 3-Z-[1-(4-((2-hydroxy-ethyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (117) 3-Z-[1-(4-((2-methoxy-ethyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (118) 3-Z-[1-(4-((2-dimethylamino-ethyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (119) 3-Z-[1-(4-((3-dimethylamino-propyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (120) 3-Z- [1-(4-((N-tert.butoxycarbonyl-2-amino-ethyl)-aminomethyl) -anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (121) 3-Z-[1-(4-((N-tert.butoxycarbonyl-3-amino-propyl)-amino methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (122) 3-Z-[1-(4-((2-amino-ethyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (123) 3-Z-[1-(4-((3-amino-propyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (124) 3-Z-[1-(4-((2-acetylamino-ethyl)-amino-methyl)-anilino) 1-phenyl-me thylene]-6-e t hoxycarbony1-2-indolinone (125) 3-Z-[1-(4-((3-acetylamino-propyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (126) 3-Z-[l-(4-((2-methylsulphonylamino-ethyl)-amino-methyl) anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (127) 3-Z-[1-(4-((3-methylsulphonylamino-propyl)-amino-methyl) -anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (128) 3-Z-[l-(4-(N-(N-tert.butoxycarbonyl-2-amino-ethyl)-N-methyl-amino-methyl)-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2-indolinone (129) 3-Z- [1-(4-(N-(2-amino-ethyl)-N-methyl-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (130) 3-Z-[1-(4-(N-(2-acetylamino-ethyl)-N-methyl-aminomethyl) -anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (131) 3-Z-[1-(4-(N-(2-methylsulphonylamino-ethyl)-N-methyl-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-indolinone (132) 3-Z-[1-(4-(carboxymethyl-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (133) 3-Z-[1-(4-(ethoxycarbonylmethyl-amino-methyl)-anilino) 1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (134) 3-Z-[1-(4-(carbamoylmethyl-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (135) 3-Z-[1-(4-(dimethylcarbamoyl-methyl-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (136) 3-Z-[1-(4-(methylcarbamoyl-methyl-amino-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (137) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-amino-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl 2-indolinone (138) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-nitro-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl 2-indolinone (13 9) 3-Z-[l-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-acetylamino-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (14 0) 3-Z- [1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-methylsulphonylamino-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (141) 3-Z- [1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-cyano-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (142) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-hydroxy-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (143) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-methoxy-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (144) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-ethoxycarbonyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (145) 3-Z- [1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-carboxy-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (146) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-carbamoyl-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (147) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-chloro-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl 2-indolinone (148) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-fluoro-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl 2-indolinone (149) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino)-3-bromo-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (150) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-methyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (151) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-trifluoromethyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (152) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3,5-dibromo-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (153) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3,5-dichloro-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (154) 3-Z-[1-(4-(dimethylaminomethyl)-3-amino-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (155) 3-Z-[1-(4-(dimethylaminomethyl)-3-nitro-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (156) 3-Z-[1-(4-(dimethylaminomethyl)-3-acetylamino-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (157) 3-Z-[1-(4-(dimethylaminomethyl)-3-(methylsulphonylamino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (158) 3-Z-[1-(4-(dimethylaminomethyl)-3-cyano-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (159) 3-Z-[1-(4-(dimethylaminomethyl)-3-hydroxy-anilino)-1 phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (160) 3-Z-[1-(4-(dimethylaminomethyl)-3-methoxy-anilino)-1 phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (161) 3-Z-[1-(4-(dimethylaminomethyl)-3-(ethoxycarbonyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone t (162) 3-Z-[1-(4-(dimethylaminomethyl)-3-carboxy-anilino)-1 phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (163) 3-Z-[1-(4-(dimethylaminomethyl)-3-carbamoyl-anilino) phenyl-methylene]-6 -ethoxycarbonyl-2 -indolinone (164) 3-Z-[1-(4-(dimethylaminomethyl)-3-chloro-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (165) 3-Z-[1-(4-(dimethylaminomethyl)-3-fluoro-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (166) 3-Z-[1-(4-(dimethylaminomethyl)-3-bromo-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (167) 3-Z-[1-(4-(dimethylaminomethyl)-3-methyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (168) 3-Z-[1-(4-(dimethylaminomethyl)-3-trifluoromethyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (169) 3-Z-[1-(4-(dimethylaminomethyl)-3,5-dibromo-anilino)■ phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (170) 3-Z-[1-(4-(dimethylaminomethyl)-3,5-dichloro-anilino) phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (171) 3-Z-[1-(4-(N-((4-methyl-piperazin-l-yl)-methylcarbonyl) N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl 2-indolinone (172) 3-Z-[1-(4-(N-(imidazo-l-yl-methylcarbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (173) 3-Z- [1- (4- (N-,'(phthalimido-2-yl-methylcarbonyl) -N-methyl amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (174) 3-Z-[1-(4-(N-aminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (175) 3-Z-[1-(4-(N-acetylaminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (176) 3-Z-[1-(4-(N-methylsulphonylaminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 indolinone (177) 3-Z-[1-(4-(N-((N-(2-methoxyethyl)-N-methyl-amino)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6 -ethoxycarbonyl-2-indo1inone (178) 3-Z-[1-(4-(N-((N-(2-dimethylaminoethyl)-N-methyl-amino) methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6 -ethoxycarbonyl-2-indolinone (179) 3-Z-[1-(4-(N-((di-(2-hydroxyethyl)-amino)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6 -ethoxycarbonyl-2-indolinone (180) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-methylene]-6-ethoxycarbonyl-2-indolinone (181) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-ethylidene]-6-ethoxycarbonyl-2-indolinone (182) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino)-anilino)-propylidene]-6-ethoxycarbonyl-2-indolinone (183) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-butylidene]-6-ethoxycarbonyl-2-indolinone (184) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-methylene]-6 ethoxycarbonyl-2 -indolinone (185) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-ethylidene]-ethoxycarbonyl-2 -indolinone (186) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-propylidene] ethoxycarbonyl-2 -indolinone (187) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-butylidene]-ethoxycarbonyl-2-indolinone (188) 3-Z-[1-(4-(N-dimethylaminocarbonylmethyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (189) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino) anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (190) 3-Z-[1-(4-((imidazolidin-2,4-dion-5-ylidene)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (191) 3-Z-[1-(4-(N-((2-dimethylamino-ethyl)-carbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl 2-indolinone (192) 3-Z-[1-(4-(N-tert.butoxycarbonyl-aminomethyl)-anilino) 1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (193) 3-Z-[1-(4-(2-oxo-pyrrolidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (194) 3-Z-[1-(4-(N-aminocarbonylmethyl-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl- 2-indolinone (195) 3-Z-[1-(4-(N-cyanomethyl-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (196) 3-Z-[1-(4-(2-(imidazol-4-yl)-ethyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (197) 3-Z-[1-(4-((2-(N-benzyl-N-methyl-amino)-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (198) 3-Z-[1-(4-cyclohexylamino-anilino)-1-phenyl-methylene] 6-ethoxycarbonyl-2-indolinone (199) 3-Z-[1-(4-(imidazol-1-yl-methyl)-anilino)-1-phenyl-methylene ]-6-ethoxycarbonyl-2-indolinone (200) 3-Z-[1-(4-(imidazol-1-yl-methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (201) 3-Z-[1-(N-methyl-piperidine-4-yl-amino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (202) 3-Z-[1-(4-(imidazol-4-yl-methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (203) 3-Z-[1-(4-((4-hydroxy-piperidin-l-yl)-methyl)-anilino)-1-phenyl-methylene]-6 -ethoxycarbonyl-2 -indolinone (204) 3-Z-[1-(4-((4-methoxy-piperidin-l-yl)-methyl)-anilino)- 1-phenyl-methylene]-6 -ethoxycarbonyl-2 -indolinone (205) 3-Z-[1-(4-benzyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone I (206) 3-Z-[1-(4-(N-(3-trifluoroacetylamino-propyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (207) 3-Z-[l-(4-(4-tert.butoxycarbonyl-piperazin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (208) 3-Z-[1-(4-(1-methyl-imidazol-2-yl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (209) 3-Z-[1-(4-(1-methyl-imidazol-2-yl) -anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (210) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-3-amino-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl- 2-indolinone (211) 3-Z-[1-(4-((3-(N-benzyl-N-methyl-amino)-propyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2-indolinone (212) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (213) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-butyryl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (214) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-isobutyryl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (215) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-benzoyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (216) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-3 amino-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (217) 3-Z-[1-(4-(4-hydroxymethyl-piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (218) 3-Z-[1-(4-(2-(4-hydroxy-piperidin-l-yl)-ethyl)-anilino 1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (219) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-propylsulphonyl amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl- 2-indolinone (220) 3-Z- [1-(4-(N-(2-dimethylamino-ethyl)-N-butylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (221) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-phenylsulphonyl amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (222) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-benzylsulphonyl amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (223) 3-Z-[1-(4-((imidazolidin-2,4-dion-5-yl)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (224) 3-Z-[1-(4-((3-hydroxy-pyrrolidin-l-yl)-methyl)-anilino) 1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (225) 3-Z-[1-(4-(cyclohexylyl-methyl)-anilino)-1-phenyl-methylene] -6-et hoxyc arbonyl-2 -indo1inone (226) 3-Z-[1-(4-(cyclohexyl-carbonyl)-anilino)-1-phenyl-methylene ]-6 -ethoxycarbonyl-2-indolinone I (227) 3-Z-[1-(4-diethylaminomethyl-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (228) 3-Z-[1-(4-(N-(n-hexyl)-N-methyl-aminomethyl)-anilino) -1 phenyl-methylene]-6 -ethoxycarbonyl-2 -indolinone (229) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-(furan-2-carbonyl)-amino)-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (230) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-(2-methoxy-benzoyl) -amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl 2-indolinone (231) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-(pyridine-3-carbonyl)-amino)-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (232) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-(phenyl-acetyl)-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (233) 3-Z- [1-(4- (imidazol-2-yl)-anilino)-1-phenyl-methylene]-6 -e thoxycarbonyl-2 -indolinone (234) 3-Z-[1-(4-(l-ethyl-imidazol-2-yl)-anilino)-1-phenyl-methylene ]-6-ethoxycarbonyl-2 -indolinone (235) 3-Z-[1-(4-(l-benzyl-imidazol-2-yl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (236) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-isopropylsulphonyl-amino)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (237) 3-Z- [1- (4- (N-,'( (4-benzyl-piperazin-l-yl) -methylcarbonyl) N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl 2-indolinone (238) 3-Z-[1-(4-(N-(pyrrolidin-1-yl-methylcarbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (239) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-3-bromo-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (240) 3-Z-[1-(4-(5-methyl-imidazol-4-yl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (241) 3-Z-[1-(4-(N-((2-dimethylamino-ethyl)-carbonyl)-N-isopropyl-amino)-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (242) 3-Z-[1-(4-(N-((2-dimethylamino-ethyl)-carbonyl)-N-benzyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (243) 3-Z-[1-(4-(N-butyl-N-tert.butoxycarbonyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (244) 3-Z-[1-(4-(N-((N-aminocarbonylmethyl-N-methyl-amino)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6 -ethoxycarbonyl-2 -indolinone (245) 3-Z-[1-(4-(N-((N-benzyl-N-methyl-amino)-methylcarbonyl) N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl 2-indolinone (246) 3-Z- [1- (4- (N-.'(di- (2-methoxyethyl) -amino-methylcarbonyl) N-methyl-amino)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl 2-indolinone (247) 3-Z-[1-(4-(N-((2-(4-tert.butoxycarbonyl-piperazin-l-yl) ethyl)-carbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene] 6-ethoxycarbonyl-2-indolinone (248) 3-Z-[1-(4-(N-((2-(piperidin-l-yl)-ethyl)-carbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (249) 3-Z- [1-(4-(N-((2-(N-benzyl-N-methyl-amino)-ethyl)-carbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (250) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-isopropyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (251) 3-Z-[1-(4-(N-(piperidin-l-yl-methylcarbonyl)-N-isopropyl-amino)-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (252) 3-Z-[1-(4-(N-((4-tert.butoxycarbonyl-piperazin-l-yl)-methylcarbonyl)-N-isopropyl-amino)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (253) 3-Z- [1-(4-(N-((N-benzyl-N-methyl-amino)-methylcarbonyl) N-benzyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl 2-indolinone (254) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-benzyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (255) 3-Z- [1- (4- (N-,'(piperidin-l-yl-methylcarbonyl) -N-benzyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (256) 3-Z-[1-(4-(l,2,4-triazol-2-yl-methyl)-anilino)-1-phenyl methylene]-6 -ethoxycarbonyl-2 -indolinone (257) 3-Z-[1-(4-(l,2,3-triazol-2-yl-methyl)-anilino)-1-phenyl methylene]-6-ethoxycarbonyl-2 -indolinone (258) 3-Z- [1-(4-(1,2,3-triazol-l-yl-methyl)-anilino)-1-phenyl methylene]-6 -ethoxycarbonyl-2-indolinone (259) 3-Z-[1-(4-((N-aminocarbonylmethyl-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (260) 3-Z-[1-(4-((di-(2-methoxy-ethyl)-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (261) 3-Z-[1-(4-((di-(2-hydroxy-ethyl)-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (262) 3-Z-[1-(4-((N-ethoxycarbonylmethyl-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (263) 3-Z-[1-(4-(azetidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2 -indolinone (264) 3-Z-[1-(4-(N-propyl-N-tert.butoxycarbonyl-aminomethyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (265) 3-Z-[1-(4-((N-(2-(2-methoxy-ethoxy)-ethyl)-N-methyl-amino) -methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (266) 3-Z-[1-(4-((N-(tert.butoxycarbonyl-3-amino-propyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2-indolinone (267) 3-Z-[1-(4-((N-(methylcarbamoyl-methyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (268) 3-Z- [1-(4-((N-(dimethylcarbamoyl-methyl)-N-methyl-amino) -methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (269) 3-Z- [1-(4-((N-propyl-N-methyl-amino)-methyl)-anilino)-1 phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (270) 3-Z-[1-(4-((N-(2-dimethylamino-ethyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (271) 3-Z- [1-(4-((N-(3-dimethylamino-propyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone (272) 3-Z-[1-(4-((N-(2-methoxy-ethyl)-N-methyl-amino)-methyl) anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (273) 3-Z-[1-(4-((N-(2-hydroxy-ethyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (274) 3-Z-[1-(4-((N-(dioxolan-2-yl-methyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (275) 3-Z-[1-(4-(3-oxo-piperazin-l-yl-methyl)-anilino)-1-phenyl -methylene] - 6ethoxycarbonyl -2 - indol inone (276) 3-Z-[1-(4-(N-(piperazin-1-yl-methylcarbonyl)-N-isopropyl-amino)-anilino)-1-phenyl-methylene]-6- ethoxycarbonyl-2 -indolinone (277) 3-Z-[1-(4-(N-((2-(piperazin-l-yl)-ethyl)-carbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (278) 3-Z-[1-(4-((N-(3-amino-propyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (279) 3-Z-[1-(4-(N-(3-methylamino-propyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (280) 3-Z-[1-(4-Ureidomethyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (281) 3-Z-[1-(4-guanidinomethyl-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (282) 3-Z-[1-(4-(N-methylsulphonyl-aminomethyl)-anilino)-1-phenyl-methylene]-6 -ethoxycarbonyl-2-indolinone (283) 3-Z-[1-(4-(4-benzoyl-piperazin-l-yl-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2 -indolinone (284) 3-Z- [1-(4-((N-(3-acetylamino-propyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (285) 3-Z- [1-(4-((N-(3-methylsulphonylamino-propyl)-N-methyl-amino) -methyl)-anilino)-1-phenyl-methylene]- 6-ethoxycarbonyl-2-indolinone / (286) 3-Z-[1-(4-((N-carboxymethyl-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone (287)3-Z-(1-anilino-l-phenyl-methylene)-6-methoxycarbonyl-2-indolinone (288) 3-Z- [1-(4-nitro-anilino)-1-phenyl-methylene]-6-methoxy-carbonyl-2-indolinone (289) 3-Z- [1-(4-fluoro-anilino)-1-phenyl-methylene]-6-methoxy carbonyl-2 -indolinone (290) 3-Z-[1-(4-chloro-anilino)-1-phenyl-methylene]-6-methoxy carbonyl-2-indolinone (291) 3-Z-[1-(4-bromo-anilino)-1-phenyl-methylene]-6-methoxy-carbonyl-2 -indolinone (292) 3-Z-[1-(4-iodo-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (293) 3-Z- [1-(4-cyano-anilino)-1-phenyl-methylene]-6-methoxycarbonyl -2-indolinone (294) 3-Z-[1-(4-carboxy-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (295) 3-Z-[1-(4-methoxy-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (296) 3-Z-[1-(4-ethoxy-anilino)-1-phenyl-methylene]-6-methoxy-carbonyl-2 -indolinone (297) 3-Z-[1-(4-trifluoromethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone i (298) 3-Z-[1-(4-methylmercapto-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (299) 3-Z-[1-(4-(isopropylaminomethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (300) 3-Z-[1-(4-(anilinomethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (301) 3-Z-[1-(4-(isobutylaminomethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (302) 3-Z-[1-(4-(cyclohexylaminomethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (303) 3-Z-[1-(4-(benzylaminomethyl)-anilino)-1-phenyl-methylene] -6-met hoxyc arbonyl-2-indolinone (304) 3-Z-[1-(4-((N-methyl-N-propyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (305) 3-Z-[1-(4-((N-isopropyl-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (306) 3-Z-[1-(4-((N-ethyl-N-propyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (307) 3-Z-[1-(4-((N-ethyl-N-isopropyl-amino)-methyl)-anilino) 1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (308) 3-Z-[1-(4-(dipropylaminomethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone (309) 3-Z-[1-(4-(diisopropylaminomethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone i (310) 3-Z-[1-(4-((N-benzyl-N-ethyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (311) 3-Z- [1-(4-(dibenzylaminomethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (312) 3-Z-[1-(4-(3,6-dihydro-2H-pyridin-l-yl-methyl)-anilino) 1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (313) 3-Z- [1- (4-(3,5-dimethyl-piperidin-l-yl-methyl)-anilino) 1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (314) 3-Z-[1-(4-(azepan-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (315) 3-Z- [1-(4-(2-amino-ethyl)-anilino)-1-phenyl-methylene]-6-methoxycarbony1-2-indo1inone (316) 3-Z-[1-(4-(2-methylamino-ethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (317) 3-Z-[1-(4-(2-ethylamino-ethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone (318) 3-Z-[1-(4-(2-dimethylamino-ethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (319) 3-Z-[1-(4-(2-diethylamino-ethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (320) 3-Z-[1-(4-(2-piperidin-l-yl-ethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone (321) 3-Z-[1-(4-(2-acetylamino-ethyl)-anilino)-1-phenyl- methylene] -6-methoxycarbonyl-2-indolinone / (322) 3-Z-[1-(4-(3-amino-propyl)-anilino)-1-phenyl-methylene 6-methoxycarbonyl-2-indolinone (323) 3-Z-[1-(4-(3-dimethylamino-propyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone (324) 3-Z-[1-(4-(N-aminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (325) 3-Z-[1-(4-(N-ethylaminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (326) 3-Z-[1-(4-(N-diethylaminomethylcarbonyl-N-methyl-amino anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (327) 3-Z-[1-(4-(N-dipropylaminomethylcarbonyl-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (328) 3-Z-[1-(4-(N-((N-ethyl-N-methyl-amino)-methylcarbonyl) N-methyl-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone (329) 3-Z-[1-(4-(N-((N-ethyl-N-propyl-amino)-methylcarbonyl) N-methyl-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone (330) 3-Z-[1-(4-(N-((N-methyl-N-propyl-amino)-methylcarbonyl) N-methyl-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone (331) 3-Z- [1-(4-(N-dimethylaminomethylcarbonyl-N-ethyl-amino) anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (332) 3-Z- [1-(4-(N-dimethylaminomethylcarbonyl-N-propyl-amino) -anilino) -1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (333) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-butyl-amino) anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (334) 3-Z-[1-(4-(N-(2-amino-ethylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (335) 3-Z-[1-(4-(N-(2-diethylamino-ethylcarbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (336) 3-Z-[1-(4-(N-acetyl-N-(2-aminoethyl)-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (337) 3-Z- [1- (4-(N-acetyl-N-(2-methylamino-ethyl)-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (338) 3-Z- [1-(4-(N-acetyl-N-(3-methylamino-propyl)-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (339) 3-Z-[1-(4-(N-acetyl-N-(2-piperidin-l-yl-ethyl)-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (340) 3-Z-[1-(4-(N-acetyl-N-(aminocarbonylmethyl)-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (341) 3-Z-[1-(4-(N-acetyl-N-(piperidin-l-yl-carbonylmethyl)-amino)-anilino)-1-phenyl-methylene]- 6-methoxycarbonyl-2 -indolinone (342) 3-Z-[1-(4-(N-methyl-N-(aminocarbonyl)-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (343) 3-Z-[1-(4-(N-methyl-N-(methylaminocarbonyl)-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (344) 3-Z-[1-(4-(N-methyl-N-(dimethylaminocarbonyl)-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (345) 3-Z-[1-(4-(N-methyl-N-(piperidin-1-yl-carbonyl)-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (346) 3-Z-[1-(4-(N-(2-ethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (347) 3-Z-[1-(4-(N-(2-diethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (348) 3-Z-[1-(4-(N-(2-pyrrolidin-l-yl-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbony1-2-indolinone (349) 3-Z-[1-(4-(N-(2-piperidin-l-yl-ethyl)-N-methylsulphonyl amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (350) 3-Z-[1-(4-(N-(2-piperazin-l-yl-ethyl)-N-methylsulphonyl amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (351) 3-Z- [1- (4- (N- (2- (4-morpholin-l-yl) -ethyl) -INT-met hyl sulphonyl-amino) -anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (352) 3-Z-[1-(4 -(N-(ethylaminocarbonylmethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (353) 3-Z- [1- (4- (N-,'(diethylaminocarbonylmethyl) -N- methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (354) 3-Z-[1-(4-(N-(pyrrolidin-1-yl-carbonylmethyl)-N-methylsulphonyl -amino) -anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone (355) 3-Z-[1-(4-(N-(piperidin-l-yl-carbonylmethyl)-N-methyl-sulphonyl-amino)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone (356) 3-Z-[1-(4-(N-(piperazin-l-yl-carbonylmethyl)-N-methylsulphonyl -amino) -anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2-indolinone (357) 3-Z-[1-(4-(N-((morpholin-4-yl)-carbonylmethyl)-N-methylsulphonyl -amino) -anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2-indolinone (358) 3-Z- [1-(4-(2-dimethylamino-ethoxy)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone (359) 3-Z-[1-(4-(3-dimethylamino-propoxy)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (360) 3-Z-[1-(4-(aminocarbonylmethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone (361) 3-Z- [1-(4-(2-aminocarbonyl-ethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone (362) 3-Z-[1-(4-(pyridin-2-yl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (363) 3-Z-[1-(4-(pyridine-3-yl)-anilino)-1-phenyl-methylene]-6 - me t hoxyc arbonyl - 2 „- i ndo 1 inone (364) 3-Z-[1-(4((N-phenethyl-N-methyl-amino)-methyl)-anilino) 1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (365) 3-Z-[1-(4-(N-acetyl-N-methyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (366) 3-Z-[l-(4-(N-ethylcarbonyl-N-(dimethylaminocarbonylmethyl) -amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl 2-indolinone (367) 3-Z-[1-(4-(N-methyl-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (368) 3-Z-[1-(4-carboxymethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (369) 3-Z-[1-(4-carbamoylmethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (370) 3-Z-[l-(4-dimethylcarbamoylmethyl-anilino)-1-phenyl-methylene ]-6-methoxycarbonyl-2 -indolinone (371) 3-Z-[1-(4-tetrazol-5-yl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (372) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-methylene]-6 -me thoxycarbonyl-2-indolinone (373) 3-Z-[1-(4-(piperidin-l-yl-methyl)-anilino)-ethylidene]-6-methoxycarbonyl-2 -indolinone (374) 3-Z- [1-(4-(piperidin-l-yl-methyl)-anilino)-propylidene] 6 -methoxycarbonyl-2 -indolinone / (375) 3-Z- [1-(4-(piperidin-l-yl-methyl)-anilino)-butylidene]-6-methoxycarbonyl-2-indolinone (376) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-anilino)-methylene]-6-methoxycarbonyl-2-indolinone (377) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-anilino)-ethylidene]-6-methoxycarbonyl-2-indolinone (378) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-anilino)-propylidene]-6-methoxycarbonyl-2-indolinone (379) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-anilino)-butylidene]-6-methoxycarbonyl-2-indolinone (380) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-methylene]-6-methoxycarbonyl-2-indolinone (381) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-ethylidene]-6-methoxycarbonyl-2-indolinone (382) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-propylidene]-6-methoxycarbonyl-2-indolinone (383) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-butylidene]-6-methoxycarbonyl-2-indolinone (384) 3-Z-[1-(4-tetrazol-5-yl-anilino)-methylene] -6-methoxy-carbonyl-2 -indolinone (385) 3-Z-[1-(4-tetrazol-5-yl-anilino)-ethylidene]-6-methoxy-carbonyl-2 -indolinone (386) 3-Z-[1-(4-tetrazol-5-yl-anilino)-propylidene]-6-methoxy carbonyl-2 -indolinone / (387) 3-Z- [1-(4-tetrazol-5-yl-anilino)-butylidene]-6-methoxy-carDonyl-2 -indolinone (388) 3-Z-[1-(4-carboxy-anilino)-methylene]- 6-methoxycarbonyl 2-indolinone (389) 3-Z-[1-(4-carboxy-anilino)-ethylidene] -6-methoxycarbonyl-2 -indolinone (390) 3-Z-[1-(4-carboxy-anilino)-propylidene]-6-methoxy-carbonyl-2 -indolinone (391) 3-Z-[1-(4-carboxy-anilino)-butylidene]-6-methoxycarbonyl-2 -indolinone (392) 3-Z-[1-(4-(N-benzyl-N-methyl-aminomethyl)-anilino)-1-methyl-methylene]-6-methoxycarbonyl-2-indolinone (393) 3-Z- [1-(4-(2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl) -anilino)-1-methyl-methylene]-6-methoxycarbonyl-2-indolinone (394) 3-Z-[1-(4-((benzo(1,3)dioxol-5-yl-methyl)-methyl-aminomethyl) -anilino)-1-methyl-methylene]-6-methoxycarbonyl-2-indolinone (395) 3-Z-[1-(4-(N-phenethyl-N-methyl-aminomethyl)-anilino) methyl-methylene]-6-methoxycarbonyl-2 -indolinone (396) 3-Z-[1-(4-(N-(3,4-dimethoxy-benzyl)-N-methyl-aminomethyl) -anilino)-1-methyl-methylene]- 6-methoxycarbonyl-2 -indolinone (397) 3-Z-[1-(4-(N-(4-Chloro-benzyl)-N-methyl-amino-methyl) anilino)-1-methyl-methylene]-6-methoxycarbonyl-2-indolinone (398) 3-Z-[1-(4-(N-(4-methylbenzyl)-N-methyl-amino-methyl)-anilino)-1-methyl-methylene]-6-methoxycarbonyl-2-indolinone (399) 3-Z- [1-(4-(N-(4-fluoro-benzyl)-N-methyl-amino-methyl) anilino)-1-methyl-methylene]-6-methoxycarbonyl-2-indolinone (400) 3-Z-[1-(4-(N-(4-bromo-benzyl)-N-methyl-amino-methyl)-anilino)-1-methyl-methylene]-6-methoxycarbonyl-2-indolinone (401) 3-Z-[1-(4-(N-(3-dimethylamino-propionyl)-N-dimethylaminocarbonylmethyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2 -indolinone (402) 3-Z-[1-(4-(N-(4-dimethylamino-butyryl)-N-dimethylaminocarbonylmethyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (403) 3-Z-[1-(4-(N-dimethylaminocarbonylmethyl-N-(2-dimethylamino-ethylsulphonyl)-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (404) 3-Z-[1-(4-(N-dimethylaminocarbonylmethyl-N-(3-dimethylamino-propylsulphonyl)-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (405) 3-Z-[1-(4-((2-hydroxy-ethyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (406) 3-Z-[1-(4-((2-methoxy-ethyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (407) 3-Z-[1-(4-((2-dimethylamino-ethyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone I (408) 3-Z-[1-(4-((3-dimethylamino-propyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (409) 3-Z-[1-(4-((N-tert.butoxycarbonyl-2-amino-ethyl)-aminomethyl) -anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (410) 3-Z-[1-(4-((N-tert.butoxycarbonyl-3-amino-propyl)-amino methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (411) 3-Z-[1-(4-((2-amino-ethyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (412) 3-Z-[1-(4-((3-amino-propyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (413) 3-Z-[1-(4-((2-acetylamino-ethyl)-amino-methyl)-anilino) 1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (414) 3-Z-[1-(4-((3-acetylamino-propyl)-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (415) 3-Z-[1-(4-((2-methylsulphonylamino-ethyl)-amino-methyl) anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (416) 3-Z-[1-(4-((3-methylsulphonylamino-propyl)-aminomethyl) -anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (417) 3-Z- [1-(4-(N-(N-tert.butoxycarbonyl-2-amino-ethyl)-N-methyl-amino-methyl)-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone (418) 3-Z-[1-(4-(N-(2-amino-ethyl)-N-methyl-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (419) 3-Z-[1-(4-(N-(2-acetylamino-ethyl)-N-methyl-aminomethyl) -anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (420) 3-Z-[1-(4-(N-(2-methylsulphonylamino-ethyl)-N-methyl-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl 2-indolinone (421) 3-Z-[1-(4-(carboxymethyl-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (422) 3-Z- [1-(4-(ethoxycarbonylmethyl-amino-methyl)-anilino) 1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (423) 3-Z-[1-(4-(carbamoylmethyl-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (424) 3-Z-[1-(4-(dimethylcarbamoyl-methyl-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (425) 3-Z-[1-(4-(methylcarbamoyl-methyl-amino-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (426) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-amino-anilino)-1-phenyl-methylene]-6-methoxycarbonyl 2-indolinone (427) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-nitro-anilino)-1-phenyl-methylene]-6-methoxycarbonyl 2-indolinone (428) 3-Z-[1-(4-(N-£imethylaminomethylcarbonyl-N-methyl-amino) -3-acetylamino-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2-indolinone (429) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-methylsulphonylamino-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (430) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-cyano-anilino)-1-phenyl-methylene] -6-methoxycarbonyl 2-indolinone (431) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-hydroxy-anilino)-1-phenyl-methylene] -6- methoxycarbonyl-2 -indolinone (432) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-methoxy-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone (433) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-ethoxycarbonyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (434) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-carboxy-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2-indolinone (435) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-carbamoyl-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone (436) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-chloro-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone (437) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-fluoro-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2-indolinone (438) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-bromo-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (439) 3-Z-[l-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-methyl-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2 -indolinone (440) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3-trifluoromethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (441) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3,5-dibromo-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2-indolinone (442) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -3,5-dichloro-anilino)-1-phenyl-methylene]-6- methoxycarbonyl-2-indolinone (443) 3-Z-[1-(4-(dimethylaminomethyll-3-amino-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (444) 3-Z-[1-(4-(dimethylaminomethyl)-3-nitro-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (445) 3-Z-[1-(4-(dimethylaminomethyl)-3-acetylamino-anilino) 1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (446) 3-Z-[1-(4-(dimethylaminomethyl)-3-methylsulphonylamino anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone / (447) 3-Z-[1-(4-(dimethylaminomethyl)-3-cyano-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (448) 3-Z-[1-(4-(dimethylaminomethyl)-3-hydroxy-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (449) 3-Z-[1-(4-(dimethylaminomethyl)-3-methoxy-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (450) 3-Z-[1-(4 -(dimethylaminomethyl)-3-ethoxycarbonyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (451) 3-Z-[1-(4-(dimethylaminomethyl)-3-carboxy-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (452) 3-Z-[1-(4-(dimethylaminomethyl)-3-carbamoyl-anilino)-1 phenyl-methylene]-6-methoxycarbonyl-2-indolinone (453) 3-Z-[1-(4-(dimethylaminomethyl)-3-chloro-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (454) 3-Z-[1-(4-(dimethylaminomethyl)-3-fluoro-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (455) 3-Z-[1-(4-(dimethylaminomethyl)-3-bromo-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (456) 3-Z-[1-(4-(dimethylaminomethyl)-3-methyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (457) 3-Z-[1-(4-(dimethylaminomethyl)-3-trifluoromethyl-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (458) 3-Z-[1-(4-dimethylaminomethyl-3,5-dibromo-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone I (459) 3-Z-[l-(4-(dimethylaminomethyl)-3,5-dichloro-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (460) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-[(2-hydroxy-ethoxy)-carbonyl]-2-indolinone (461) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-[(ethoxycarbonyl-methoxy)-carbonyl]-2-indolinone (462) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-[(carboxy-methoxy)-carbonyl]-2-indolinone (463) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-[(carbamoyl-methoxy)-carbonyl]-2-indolinone (464) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-1-phenyl-methylene] -6-[(2-hydroxy-ethoxy)-carbonyl]-2-indolinone (465) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-[(ethoxycarbonyl-methoxy)-carbonyl]-2-indolinone (466) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-[(carboxy-methoxy)-carbonyl]-2-indolinone (467) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-[(carbamoyl-methoxy)-carbonyl]-2-indolinone (468) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-[(2-methoxy-ethoxy)-carbonyl]-2-indolinone (469) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-[(2-dimethylamino-ethoxy)-carbonyl]-2-indolinone (470) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-[(2-(N- tert.butoxycarbonyl-amino)-ethoxy)-carbonyl]-2-indolinone (471) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-[(2-amino-ethoxy)-carbonyl]-2-indolinone (472) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-[(2,2,2- trifluoroethoxy)-carbonyl]-2-indolinone (473) 3-Z-[1-(4-(N-((4-methyl-piperazin-l-yl)-methylcarbonyl) N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2 -indolinone (474) 3-Z-[1-(4-(N-(imidazo-1-yl-methylcarbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (475) 3-Z-[1-(4-(N-(phthalimido-2-yl-methylcarbonyl)-N-methyl amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (476) 3-Z-[1-(4-(N-aminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (477) 3-Z- [1-(4- (N-acetylaminomethylcarbonyl-N-methyl-amino) anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (478) 3-Z-[1-(4-(N-methylsulphonylaminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl 2-indolinone ' (479) 3-Z-[1-(4-(N-((N-(2-methoxyethyl)-N-methyl-amino)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene] 6-methoxycarbonyl-2 -indolinone (480) 3-Z-[1-(4-(N-((N-(2-dimethylaminoethyl)-N-methyl-amino methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene] 6-methoxycarbonyl-2 -indolinone (481) 3-Z-[1-(4-(N-((di-(2-hydroxyethyl)-amino)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene] 6-methoxycarbonyl-2-indolinone (482) 3-Z-[1-(4-tert.butoxycarbonylmethyl-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (483) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-methylene]-6-methoxycarbonyl-2-indolinone (484) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-ethylidene]-6-methoxycarbonyl-2-indolinone (485) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-propylidene]-6-methoxycarbonyl-2-indolinone (486) 3-Z-[1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino) -anilino)-butylidene]-6-methoxycarbonyl-2-indolinone (487) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-methylene]-6 methoxycarbonyl-2 -indolinone (488) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-ethylidene]-methoxycarbonyl-2-indolinone (489) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-propylidene] methoxycarbonyl-2 -ijidolinone (490) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-butylidene]-methoxycarbonyl-2 -indolinone (491) 3-Z-[1-(4-tert.butyloxycarbonyl-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (492) 3-Z-[1-(4-(N-(2-dimethylamino-ethyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (493) 3-Z-[1-(4-(N-(3-dimethylamino-propyl)-N-methyl-amino) anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (494) 3-Z-[1-(4-(N-methyl-acetylamino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone (495) 3-Z- [1-(4-(imidazol-4-yl)-anilino)-1-phenyl-methylene 6-methoxycarbonyl-2-indolinone (496) 3-Z- [1-(4-( (N- (dioxolan-2-yl-methyl)-N-methyl-amino)-methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (497) 3-Z-[1-(4-(N-benzyl-N-methyl-amino-methyl)-anilino)-1 methyl-methylene]-6-carbamoyl-2-indolinone (498) 3-Z-[1-(4-(2,3,4,5-tetrahydro-benzo(d)azepin-3-yl-methyl)-anilino)-1-methyl-methylene]-6-carbamoyl-2-indolinone (499) 3-Z-[1-(4-((benzo(1,3)dioxol-5-yl-methyl)-methyl-aminomethyl) -anilino)-1-methyl-methylene]-6-carbamoyl-2-indolinone (500) 3-Z-[1-(4-(N-phenethyl-N-methyl-amino-methyl)-anilino)- 1-methyl-methylene]-6-carbamoyl-2 -indolinone / (501) 3-Z-[1-(4-(N-(3,4-dimethoxy-benzyl)-N-methyl-amino-methyl) -anilino)-1-methyl-methylene]-6-carbamoyl-2-indolinone (502) 3-Z-[1-(4-(N-(4-Chloro-benzyl)-N-methyl-amino-methyl)-anilino)-1-methyl-methylene]-6-carbamoyl-2-indolinone (503) 3-Z-[1-(4-(N-(4-methyl-benzyl)-N-methyl-amino-methyl)-anilino)-1-methyl-methylene]-6-carbamoyl-2-indolinone (504) 3-Z-[1-(4-(N-(4-fluoro-benzyl)-N-methyl-amino-methyl)-anilino)-1-methyl-methylene]-6-carbamoyl-2-indolinone (505) 3-Z-[1-(4-(N-(4-bromo-benzyl)-N-methyl-amino-methyl)-anilino)-1-methyl-methylene]-6-carbamoyl-2-indolinone (506) 3-Z-[1-(4-((N-(2-methoxy-ethyl)-N-methyl-amino)-methyl) anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone (507) 3-Z-[1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-[(2-amino-ethoxy)-carbonyl] -2-indolinone (508) 3-Z-[1-(4-((N-(3-methylsulfonylamino-propyl)-N-methyl-amino) -methyl)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl 2-indolinone Example 13 Dry ampoule containing 75 mg of active substance per 10 ml Composition: Preparation: Active substance and mannitol are dissolved in water. After packaging the solution is freeze-dried. To produce the solution ready for use, the product is dissolved in water for injections.

Example 14 Dry ampoule containing 35 mg of active substance per 2 ml Composition: Active substance 35.0 mg Mannitol 100.0 mg water for injections ad 2.0 ml Preparation: Active substance and mannitol are dissolved in water. After packaging, the solution is freeze-dried.

Active substance Mannitol I water for injections 75.0 mg 50.0 mg ad 10.0 ml To produce the solution ready for use, the product is dissolved in water for injections.

Example 15 Tablet containing 50 mg of active substance Composition: (1) Active substance 50.0 mg (2) Lactose 98.0 mg (3) Maize starch 50.0 mg (4) Polyvinylpyrrolidone 15.0 mg (5) Magnesium stearate 2 . 0 ma 215.0 mg Preparation: (1), (2) and (3) are mixed together and granulated with an aqueous solution of (4). (5) is added to the dried granulated material. From this mixture tablets are pressed, biplanar, faceted on both sides and with a dividing notch on one side. Diameter of the tablets: 9 mm.

Example 16 Tablet containing 350 mg of active substance Composition: (1) Active substance 350.0 mg (2) Lactose 13 6.0 mg (3) Maize starch 80.0 mg (4) Polyvinylpyrrolidone 30.0 mg (5) Magnesium stearate 4.0 ma 600.0 mg Preparation: (1), (2) and (3) are mixed together and granulated with an aqueous solution of (4). (5) is added to the dried granulated material. From this mixture tablets are pressed, biplanar, faceted on both sides and with a dividing notch on one side. Diameter of the tablets: 12 mm. i Example 17 Capsules containing 50 mg of active substance Composition: (1) Active substance 50.0 mg (2) Dried maize starch 58.0 mg (3) Powdered lactose 50.0 mg (4) Magnesium stearate 2.0 ma 160.0 mg Preparation: (1) is triturated with (3). This trituration is added to the mixture of (2) and (4) with vigorous mixing.

This powder mixture is packed into size 3 hard gelatine capsules in a capsule filling machine.

Example 18 Capsules containing 350 mg of active substance

Claims (19)

- 239 - Composition: (1) Active substance 350.0 mg (2) Dried maize starch 46.0 mg (3) Powdered lactose 3 0.0 mg (4) Magnesium stearate 4.0 mg 43 0.0 mg Preparation: (1) is triturated with (3). This trituration is added to the mixture of (2) and (4) with vigorous mixing. This powder mixture is packed into size 0 hard gelatine capsules in a capsule filling machine. Example 19 Suppositories containing 100 mg of active substance 1 suppository contains: Active substance 100.0 mg Polyethyleneglycol (M.W. 1500) 600.0 mg Polyethyleneglycol (M.W. 6000) 460.0 mg Polyethylenesorbitan monostearate 840.0 mg 2,000.0 mg Preparation: The polyethyleneglycol is melted together with polyethylene sorbitan monostearate. At 40°C the ground active substance is homogeneously dispersed in the melt. It is cooled to 38°C and poured into slightly chilled suppository moulds. INTELLECTUAL property office OF N.Z. 240 2 1 DEC 2094 RECEIVED Patent Claims

1. An indolinone of general formula R, (I) , r2 i Ri substituted in the 6 position, wherein X denotes an oxygen or sulphur atom, Ri denotes a hydrogen atom a Ci-4-alkoxycarbonyl or C2-4-alkanoyl group, R2 denotes a carboxy group, a straight-chain or branched Ci-6-alkoxy-carbonyl group, a C4-7-cycloalkoxy-carbonyl or an aryloxycarbonyl group, a straight-chain or branched Ci-s-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a phenyl, heteroaryl, carboxy, Ci-3-alkoxy-carbonyl, aminocarbonyl, Ci-3-alkylamino-carbonyl or di-(Ci-3-alkyl)-aminocarbonyl group, a straight-chain or branched C2-6-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a chlorine atom or a hydroxy, Ci-3-alkoxy, amino, Ci-3-alkylamino or di- (Ci-3-alkyl) -amino group, an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2 - 241 - position of the ethyl group by a hydroxy or C1_3-alkoxy group or, if R4 does not denote an aminosulphonyl-phenyl or N- (C^j-alkyl) -C1_3-alkylaminocarbonyl-phenyl group, it may also denote a di- (C^-alkyl)-aminocarbonyl group, R3 denotes a hydrogen atom, a C^.g-alkyl, C3_7-cycloalkyl, trifluoromethyl or heteroaryl group, a phenyl or naphthyl group, a phenyl or naphthyl group mono-or disubstituted by a fluorine, chlorine, bromine or iodine atom, by a trif luoromethyl, C^-alkyl or C^.-j-alkoxy group, whilst in the event of disubstitution the substituents may be identical or different and wherein the abovementioned unsubstituted as well as the mono- and disubstituted phenyl and naphthyl groups may additionally be substituted by a hydroxy, hydroxy--alkyl or C^-j-alkoxy-C-L.-j-alkyl group, by a cyano, carboxy, carboxy-C^-alkyl, C^-alkoxycarbonyl, aminocarbonyl, C-^-alkylamino-carbonyl or di - (Cx_3-alkyl) -aminocarbonyl group, by a nitro group, by an amino, Cj_.3-alkylamino, di-(C^-j-alkyl) -amino or amino-C^-alkyl group, by a C^-alkylcarbonylamino, N- (C^-j-alkyl) -C-^-alkyl-carbonylamino, - alkylcarbonylamino - - alkyl, N- (C^-alkyl) -C1.3-alkylcarbonylamino-C1.3-alkyl, C-^-alkyl-sulphonylamino, Cx_3 - alkyl sulphonylamino - - alkyl, N- (C^-alkyl) -C1_3-alkylsulphonylamino-C1_3-alkyl or aryl--alkylsulphonylamino group, - 242 - by a cycloalkylamino, cycloalkyleneimino, cycloalkyleneiminocarbonyl , cycloalkyleneimino-C1.3-alkyl, cycloalkyleneiminocarbonyl - - alkyl or cycloalkyleneiminosulphonyl-C1_3-alkyl group having 4 to 7 ring members in each case, whilst in each case the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH or -N (C1_3-alkyl) group, or by a heteroaryl or heteroaryl-C^-alkyl group, R4 denotes a C3_7-cycloalkyl group, whilst the methylene group in the 4 position of a 6- or 7-membered cycloalkyl group may be substituted by an amino, C^-alkylamino or di- (C^-alky!) -amino group or replaced by an -NH or -N (C^-alkyl) group, or a phenyl group substituted by the group R6, which may additionally be mono- or disubstituted by fluorine, chlorine, bromine or iodine atoms, by C^-alkyl, trifluoromethyl, hydroxy, C-^-alkoxy, carboxy, C^-alkoxycarbonyl, amino, acetylamino, C^-alkyl-sulphonylamino, aminocarbonyl, C^j-alkyl-aminocarbonyl, di- (C^.j- alkyl) -aminocarbonyl, aminosulphonyl, C^-alkyl-aminosulphonyl, di-(Cj.j-alkyl) -aminosulphonyl, nitro or cyano groups, wherein the substituents may be identical or different and wherein R6 denotes a hydrogen, fluorine, chlorine, bromine or iodine atom, a cyano, nitro, amino, C^s-alkyl, C3.7-cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl group, the group of formula - 243 - X™ —CH=< X N-^o H u / wherein the hydrogen atoms bound to a nitrogen atom may in each case be replaced independently of one another by a alkyl group, a C1_3-alkoxy group, a C1_3-alkoxy-C1_3-alkoxy, phenyl-C^-j-alkoxy, amino - C2.3 - alkoxy, - alkylamino - C2_3 - alkoxy, di- (C^-alkyl) - amino-C2_3-alkoxy, phenyl-C^-alkylamino-C2.3-alkoxy, N- (C^-alkyl) -phenyl-C^-alkylamino-C^-alkoxy, C5_7-cycloalkyleneimino-C2_3-alkoxy or C-^-alkylmercapto group, a carboxy, C^-alkoxycarbonyl, aminocarbonyl, -alkylamino-carbonyl, N- (C1.5-alkyl) -C^-alkylaminocarbonyl, phenyl - - alkylamino- carbonyl, N- (C-^-alkyl) -phenyl-C^-alkylamino-carbonyl, piperazinocarbonyl or N- (C1.3-alkyl) -piperazinocarbonyl group, a Q.-j-alkylaminocarbonyl or N- (C1.5-alkyl) -C^-alkylaminocarbonyl group wherein an alkyl moiety is substituted by a carboxy or C^-alkoxycarbonyl group or in the 2 or 3 position by a di- (C^-alkyl) -amino, piperazino, N- (C^-j-alkyl) -piperazino or a 4- to 7-membered cycloalkyleneimino group, a C3.7-cycloalkyl-carbonyl group, wherein the methylene group in the 4 position of the 6- or 7-membered cycloalkyl moiety may be substituted by an amino, C^-alkylamino or di - (C^-alkyl) - amino group or replaced by an -NH or -N (C^-alky!) group, a 4- to 7-membered cycloalkyleneimino group wherein - 244 - a methylene group linked to the imino group may be replaced by a carbonyl or sulphonyl group or the cycloalkylene moiety may be fused to a phenyl ring or one or two hydrogen atoms may each be replaced by a C^-alkyl group and/or in each case the methylene group in the 4 position of a 6-or 7-membered cycloalkyleneimino group may be substituted by a carboxy, C^-alkoxycarbonyl, aminocarbonyl, C1_3-alkylaminocarbonyl, di - (C^-alkyl) -aminocarbonyl, phenyl-C^-alkylamino or N-(C1.3-alkyl)-phenyl-C±_3-alkylamino group or may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (C1_3-alkyl) , -N(phenyl), -N (C1_3-alkyl-carbonyl) or -N (benzoyl) group, Cx.4 — alkyl group substituted by the group R7, wherein R7 denotes a C3.7-cycloalkyl group, whilst the methylene group in the 4 position of a 6- or 7-membered cycloalkyl group may be substituted by an amino, C^-alkylamino or di- (C-t.-j-alkyl) -amino group or replaced by an -NH or -N (C1.3-alkyl) group or in a 5- to 7-membered cycloalkyl group a -(CH2)2 group may be replaced by a -CO-NH group, a -(CH2)3 group may be replaced by a -NH-CO-NH or -CO-NH-CO group or a -(CH2) 4 group may be replaced by a -NH-CO-NH-CO group, whilst in each case a hydrogen atom bound to a nitrogen atom may be replaced by a CI-3-alkyl group, - 245 - an aryl or heteroaryl group, a hydroxy or C^-alkoxy group, an amino, C^-alkylamino, di-(C^-alkyl)-amino, phenylamino, N-phenyl-C1_3-alkyl-amino, phenyl-C1_3-alkylamino, N- (C1_3-alkyl) -phenyl-^,3-alkylamino or di- (phenyl-C1_3-alkyl) -amino group, / an co-hydroxy-C2_3-alkyl-amino, N- (C1.3-alkyl) -co-hydroxy-C2„3-alkyl-amino, di- (®-hydroxy-C2.3-alkyl) -amino, di- (co- (C1.3-alkoxy) -C2.3-alkyl) -amino or N- (dioxolan-2-yl) -C^-alkyl-amino group, a C^-alkylcarbonylamino-C^-j-alkyl-amino or C1.3-alkylcarbonylamino-C2_3-alkyl-N- (Cj^-alkyl) -amino group, a C-^-alkylsulphonylamino, N- (C-^-alkyl) -C^-alky!-sulphonylamino, C1_3-alkylsulphonylamino-C2„3-alkyl-amino or C1_3-alkylsulphonylamino-C2_3-alkyl-N- (Cx.3-alkyl) -amino group, a hydroxycarbonyl-C^j-alkylamino or N- (C^-alkyl) -hydroxycarbonyl - - alkyl - amino group, a guanidino group wherein one or two hydrogen atoms may each be replaced by a (^..j-alkyl group, a group of formula -N(R8)-CO-(CH2)n-R9 (II), wherein R8 denotes a hydrogen atom or a C^-alkyl group, - 246 - n denotes one of the numbers 0, 1, 2 or 3 and R9 denotes an amino, C^-alkylamino, di - (C^-alkyl)-amino, phenylamino, N- (C^-alkyl) -phenylamino, benzylamino, N- (C^-alkyl) -benzylamino or C-^-alkoxy group, a 4- to 7-membered cycloalkyleneimino group, whilst in each case the methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N(C1_3-alkyl) , -N(phenyl), -N (C^-alkyl-carbonyl) or -N(benzoyl) group, or, if n denotes one of the numbers 1, 2 or 3, it may also denote a hydrogen atom, a group of formula -N(R10) - (CH2)m- (C0)o-Rn (III), wherein R10 denotes a hydrogen atom, a C^-alkyl group, a C^-alkylcarbonyl, arylcarbonyl, phenyl-C^-alkylcarbonyl, -alkylsulphonyl, arylsulphonyl or phenyl--alkylsulphonyl group, m denotes one of the numbers 1, 2, 3 or 4, o denotes the number 1 or, if m denotes one of the numbers 2, 3 or 4, o may also denote the number 0 and R1X denotes an amino, C^-alkylamino, di - (C1-4 — alkyl) -amino, phenylamino, N- (Cj^-alkyl)-phenylamino, benzylamino, N- (C^-alkyl) -benzylamino, C^-alkoxy or Cx.3-alkoxy-alkoxy group, a di- (C^ -alkyl) - amino-C1.3- - 247 - alkylamino group optionally substituted in the 1 position by a C1_3-alkyl group or a 4- to 7-membered cycloalkyleneimino group, wherein the cycloalkylene moiety may be fused to a phenyl ring or in each case the methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (C^j-alkyl) , -N(phenyl), -NlC^-alkyl-carbonyl) or -N(benzoyl) <£roup, a C4_7-cycloalkylamino, C4.7-cycloalkyl-C1.3-alkylamino or C4_7-cycloalkenylamino group wherein position 1 of the ring is not involved in the double bond and wherein the abovementioned groups may each additionally be substituted at the amino-nitrogen atom by a Cs_7-cycloalkyl, C2_4-alkenyl or Cx.4-alkyl group, a 4- to 7-membered cycloalkyleneimino group, wherein the cycloalkylene moiety may be fused to a phenyl group or to an oxazolo, imidazolo, thiazolo, pyridino, pyrazino or pyrimidino group optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, Cx.3-alkyl, C^j-alkoxy or amino group, and/or one or two hydrogen atoms may each be replaced by a C^.j-alkyl, Cs_7-cycloalkyl or phenyl group and/or the methylene group in the 3 position of a 5-membered cycloalkyleneimino group may be substituted by a hydroxy, hydroxy-C^-alkyl, C1.3-alkoxy or C^_3 — alkoxy—C1_3 — alky 1 group, the methylene group in the 3 or 4 position of a 6- or 7-membered cycloalkyleneimino group may in each case be substituted by a hydroxy, hydroxy-C^-alkyl, - 248 - C^-alkoxy, C1.3-alkoxy-C1_3-alkyl, carboxy, Cx_4-alkoxycarbonyl, aminocarbonyl, C1_3-alkylaminocarbonyl, di- (C^-alkyl) -aminocarbonyl, phenyl-C^-alkylamino or N- (C^-alkyl) -phenyl-C^-alkyl-amino group or may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (C^-alkyl-), -N(phenyl), -N (phenyl-C-^-alkyl-) , -N (C^-alkyl-carbonyl-) , -N (Cx.4-hydroxy-carbonyl-) , -N (C-^-alkoxy-carbonyl- ) , -N(benzoyl-) or -N (phenyl-G^-alkyl-carbonyl - ) group, wherein a methylene group linked to an imino-nitrogen atom of the cycloalkyleneimino group may be replaced by a carbonyl or sulphonyl group or in a 5-to 7-membered monocyclic cycloalkyleneimino group or a cycloalkyleneimino group fused to a phenyl group the two methylene groups linked to the imino-nitrogen atom may each be replaced by a carbonyl group, or R6 denotes a C^-alkyl group which is substituted by a carboxy, -alkoxycarbonyl, aminocarbonyl, C1_3-alkyl aminocarbonyl or di-(C^-alkyl) -aminocarbonyl group or by a 4- to 7-membered cycloalkyleneiminocarbonyl group, an N- (C1.3-alkyl) -C2_4-alkanoylamino group which is additionally substituted in the alkyl moiety by a carboxy or Ci.j — alkoxycarbonyl group, a group of formula -N(R12)-CO-(CH2)p-Ri3 (IV), wherein - 249 - R12 denotes a hydrogen atom, a C^g-alkyl or C3.7-cycloalkyl group or a C^j-alkyl group terminally substituted by a phenyl, heteroaryl, trifluoromethyl, hydroxy, C^-alkoxy, aminocarbonyl, C1_4-alkylamino-carbonyl, di-(C^-alkyl) -amino - carbonyl, C^-alkyl-carbonyl, C1_3-alkyl-sulphonyl-amino, N- (C-^-j-alkyl) -C^-alkyl-sulphonylamino, Cj.3-alkyl-aminosulphonyl or di - (C^-j- alkyl) -aminosulphonyl group and p denotes one of the numbers 0, 1, 2 or 3 and R13 assumes the meanings of the abovementioned group R7, or, if p denotes one of the numbers 1, 2 or 3, it may also denote a hydrogen atom, a group of formula -N(R14)-(CH2)q-(CO)r-R15 (V), wherein R14 denotes a hydrogen atom, a C^-alkyl group, a Cx_3 — alkylcarbonyl, arylcarbonyl, phenyl-C1.3-alkylcarbonyl, heteroarylcarbonyl, heteroaryl -G^-alkylcarbonyl, Cj.4 — alkyl sulphonyl, aryl sulphonyl, phenyl-C1_3-alkylsulphonyl, heteroaryl sulphonyl or heteroaryl-C^-j-alkyl-sulphonyl group, q denotes one of the numbers 1, 2, 3 or 4, r denotes the number 1 or, if q is one of the numbers 2, 3 or 4, it may also denote the number 0 and R1S assumes the meanings of the abovementioned group R7, - 250 - a group of formula -N(R16)-S02-Riv (VI), wherein R16 denotes a hydrogen atom or a Cx.4-alkyl group optionally terminally substituted by a cyano, trifluoromethyl-rcarbonylamino or N-(Ci_3-alkyl)-trifluoromethyl-carbonyl-amino group and R17 denotes a C^-alkyl group, an amino group substituted by a di- (C1_3-alkyl) -amino-C^-alkyl-carbonyl or di-(C^-alkyl) -amino-C-^-alkyl-sulphonyl group and a di-(C^-alkyl) -aminocarbonyl-C1.3-alkyl group, or an N- (C1_3-alkyl)-C^s-alkylsulphonylamino or N- (C1.3-alkyl) -phenylsulphonylamino group wherein the alkyl moiety is additionally substituted by a cyano or carboxy group, wherein all the single-bonded or fused phenyl groups contained in the groups mentioned under R6 may be mono- or disubstituted by fluorine, chlorine, bromine or iodine atoms, by C^g-alkyl, trif luoromethyl, hydroxy, C-^-alkoxy, carboxy, C1.3-alkoxycarbonyl, aminocarbonyl, — alkylamino — carbonyl, di- (C1.4-alkyl) - amino-carbonyl, aminosulphonyl, -alkyl-aminosulphonyl, di - (C1-3 — alkyl) -aminosulphonyl, -alkyl-sulphonylamino, nitro or cyano groups, wherein the substituents may be identical or different, or two adjacent hydrogen atoms of the phenyl groups may be replaced by a methylenedioxy group, - 251 - and R5 denotes a hydrogen atom or a C^-alkyl group, wherein by an aryl group is meant a phenyl or naphthyl group optionally mono- or disubstituted by a fluorine, chlorine, bromine or iodine atom, by a cyano, trifluoromethyl, nitro, carboxy, aminocarbonyl, C-^-alkyl or C-^-alkoxy group and I by a heteroaryl group is meant a monocyclic 5- or 6-membered heteroaryl group optionally substituted by a C1_3-alkyl group in the carbon skeleton, wherein the 6-membered heteroaryl group contains one, two or three nitrogen atoms and the 5-membered heteroaryl group contains an imino group optionally substituted by a G^-alkyl or phenyl-C1_3-alkyl group, an oxygen or sulphur atom or an imino group optionally substituted by a C1.3-alkyl or phenyl-C1_3-alkyl group or an oxygen or sulphur atom and additionally a nitrogen atom or an imino group optionally substituted by a C^.j-alkyl or phenyl-C^-alkyl group and two nitrogen atoms, and moreover a phenyl ring may be fused to the abovementioned monocyclic heterocyclic groups via two adjacent carbon atoms and the bonding takes place via a nitrogen atom or via a carbon atom of the heterocyclic moiety or a fused phenyl ring, some or all of the hydrogen atoms in the abovementioned alkyl and alkoxy groups or in the alkyl moieties contained in the - 252 - above-defined groups of formula I may be replaced by fluorine atoms, and the hydrogen atom of any carboxy group present or a hydrogen atom bound to a nitrogen atom may each be replaced by a hydroxyl group, an acyl group, an allyloxycarbonyl group, a Ci-i6-alkoxycarbonyl group, a phenyl-Ci-6-alkoxylcarbonyl group, a Ci_3-alkylsulphonyl-C2-4-alkoxycarbonyl, Ci-3-alkoxy-C2-4-alkoxy-C2-4-alkoxycarbonyl or ReC0-0-(RfCRg)-0-CO group where Re denotes a Ci_8-alkyl, C5-7-cycloalkyl, phenyl or phenyl-Ci-3-alkyl group, Rf denotes a hydrogen atom, a Ci-3-alkyl, Cs-7-cycloalkyl or phenyl group and Rg denotes a hydrogen atom, a Ci-3-alkyl or ReC0-0-(RfCRh) -0 wherein Re and Rf are as herein before defined and Rh is a hydrogen atom or a C1-3 alkyl group, a tautomer, diastereomer, enantiomer, or a mixture thereof or a salt thereof.

2. An indolinone of general formula I according to claim 1, wherein Ri and R3 are as hereinbefore defined and X denotes an oxygen atom, R2 denotes a carboxy group, a straight-chain or branched Ci-6-alkoxy-carbonyl group, a C5-7-cycloalkoxycarbonyl or a phenoxycarbonyl group, .iilELLECTUAL PROPERTY OFFICE OF N.Z -1 MAR 2005 RFHFIVPn - 253 - a straight-chain or branched Ci-3-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a phenyl, heteroaryl, carboxy, Ci-3-alkoxycarbonyl, aminocarbonyl, Ci-3-alkylaminocarbonyl or di-(Ci-3-alkyl)-aminocarbonyl group, a straight-chain or branched C2-3~alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a chlorine atom, by a hydroxy, Ci-3-alkoxy, amino, Ci-3-alkylamino or di-(Ci-3-alkyl)-amino group, an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2 position of. the ethyl group by a hydroxy or Ci-3-alkoxy group or, if R4 does not denote an aminosulphonyl-phenyl or N-(Ci-5-alkyl)-Ci-3-alkylaminocarbonyl-phenyl group, it may also denote a di- (Ci-2-alkyl) -aminocarbonyl group, R4 denotes a C3-7-cycloalkyl group, whilst the methylene group in the 4 position of a 6- or 7-membered cycloalkyl group may be substituted by an amino, Ci-3-alkylamino or di-(Ci-3-alkyl)-amino group or replaced by an -NH or -N (Ci-3-alkyl) group, or a phenyl group substituted by the group R6, which may additionally be mono- or disubstituted by fluorine, chlorine or bromine atoms, by Ci-3-alkyl, trif luoromethyl, hydroxy, Ci-3-alkoxy, carboxy, Ci-3-alkoxycarbonyl, amino, acetylamino, aminocarbonyl, Ci-3-alkyl-aminocarbonyl, di-(Ci-3-alkyl)-aminocarbonyl, nitro or cyano groups, wherein the substituents may be identical or different 'and wherein R6 denotes a hydrogen, fluorine, chlorine, bromine or iodine atom, INTELLECTUAL PROPERTY OFFICE OF N.Z. 21 DEC 2004 - 254 - a cyano, nitro, amino, Ci-5-alkyl, C3_7-cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl group, the group of formula wherein a hydrogen atom bound to the nitrogen atom may be replaced by a Ci-3-alkyl group, a Ci-3-alkoxy group, an amino-C2-3-alkoxy, Ci_3-alkylamino-C2-3~alkoxy, di-(Ci-3-alkyl) -amino-C2-3-alkoxy, phenyl-Ci-3~alkylamino-C2-3-alkoxy, N- (Ci-3-alkyl) -phenyl-Ci-3-alkylamino-C2-3-alkoxy, pyrrolidino-C2-3-alkoxy, piperidino-C2-3~alkoxy or Ci-3-alkylmercapto group, a carboxy, Ci-4-alkoxycarbonyl, aminocarbonyl, Ci-3-alkyl-amino-carbonyl, phenyl-Ci-3-alkylamino-carbonyl or N- (Ci-3-alkyl) -phenyl-Ci-3-alkylamino-carbonyl group, a C3-7~cycloalkyl-carbonyl group, wherein the methylene group in the 4 position of the 6-or 7-membered cycloalkyl moiety may be replaced by an -NH or -N (Ci-3-alkyl) group, a 4- to 7-membered cycloalkyleneimino group, wherein a methylene group linked to the imino group may be replaced by a carbonyl or sulphonyl group or one or two hydrogen atoms may each be replaced by a Ci-3-alkyl group and/or 0, CH intellectual property office OF n.z. 2 1 DEC 200*1 aeAeiwrn - 255 - in each case the methylene group in the 4 position of a ■6- or 7-membered cycloalkyleneimino group may be substituted by a carboxy, Ci-3-alkoxycarbonyl, aminocarbonyl, Ci-3-alkylaminocarbonyl, di-(Ci-3-alkyl)-aminocarbonyl, phenyl-Ci_3-alkylamino or N-(Ci-3-alkyl)-phenyl-Ci-3-alkylamino group or may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH or -N (Ci_3-alkyl) group, a Ci-4-alkyl group terminally substituted by the group R7, wherein R7 denotes a Cs-7-cycloalkyl group, whilst the methylene group in the 4 position of a 6- or 7-membered cycloalkyl group may be replaced by an -NH or -N (Ci-3-alkyl) group or in a 5- to 7-membered cycloalkyl group a -(CH2)2 group may be replaced by a -CO-NH group, a -(CH2)3 group may be replaced by a -NH-CO-NH- or a -(CH2)4 group may be replaced by a -NH-CO-NH-CO group, whilst in each case a hydrogen atom bound to a nitrogen atom may be replaced by a Ci-3-alkyl group, a phenyl or heteroaryl group, a hydroxy or Ci-3-alkoxy group, an amino, Ci-6-alkylamino, di-(Ci-6-alkyl)-amino, phenylamino, N-phenyl-Ci-3-alkyl-amino, phenyl-Ci-3-alkylamino, N- (Ci-3-alkyl) -phenyl-Ci-3-alkylamino or di- (phenyl-Ci-3-alkyl) -amino group, "intellectual property office of n.z. 21 DEC MM - 256 - a ©-hydroxy-C2-3-alkyl-a1tri.no, N- (Ci-3-alkyl) -co-hydroxy--C2-3-alkyl-anri.no, di- (co-hydroxy-C2-3-alkyl) -amino, di- (co- (Ci-3-alkoxy) -C2-3-alkyl) -amino or N-(dioxolan-2-yl)-Ci-3-alkyl-amino group, a Ci-3-alkylcarbonylamino-C2-3-alkyl-amino or Ci-3-alkylcarbonylamino-C2-3-alkyl-N- (Ci-3-alkyl) -amino group, a Ci-3-alkylsulphonylamino, N- (Ci-3-alkyl) -Ci-3-alkylsulphonylamino, Ci-3-alkylsulphonylamino--C2-3-alkyl-a1ru.no or Ci-3-alkylsulphonylamino-C2-3-alkyl--N- (Ci-3-alkyl) -amino group, a hydro"xycarbonyl-Ci-3^alkylamino or N- (Ci-3-alkyl) -hydroxycarbonyl-Ci-3-alkyl-amino group a guanidino group wherein a hydrogen atom may be replaced by a Ci-3-alkyl group, a group of formula -N(R8)-CO-(CH2)n-R9 wherein Re denotes a hydrogen atom or a Ci-3-alkyl group, n denotes one of the numbers 0, 1, 2 or 3 and Rg denotes an amino, Ci-3-alkylamino, di-(Ci-3-alkyl) -amino, phenylamino, benzylamino or Ci_4-alkoxy group, a 5-to 7-membered cycloalkyleneimino group, wherein the methylene group in position 4 of the piperidino group may be replaced by an oxygen or sulphur atom, by an -NH, -N (Ci-3-alkyl) , -N (phenyl), -N (Ci-3-alkyl-carbonyl) - 257 - or -N(benzoyl) group, or, if n denotes one of the numbers 1, 2 or 3, it may also denote a hydrogen atom, a group of formula -N(Rio)-(CH2)m-(CO)0-Rn (III), wherein Rio denotes a hydrogen atom, a Ci-3-alkyl group, a Ci-3-alkylcarbonyl or Ci-3-alkylsulphonyl group, m denotes one of the numbers 1, 2 or 3, o denotes the number 1 or, if m is one of the numbers 2 or 3, o may also denote the number 0 and Rn denotes an amino, Ci-3-alkylamino, di-(Ci-3-alkyl)-amino, Ci-4-alkoxy or Ci_3-alkoxy-Ci-3-alkoxy group or a 5- to 7-membered cycloalkyleneimino group, wherein the methylene group in position 4 of the piperidino group may be replaced by an oxygen or sulphur atom, by an - NH, -N (Ci-3-alkyl) , -N (phenyl), -N (Ci-3-alkyl-carbonyl) or -N(benzoyl) group, a C4_7-cycloalkylamino or C4_7-cycloalkenylamino group wherein position 1 of the ring is not involved in the double bond, a 4- to 7-membered cycloalkyleneimino group, wherein the cycloalkylene moiety may be fused to a phenyl group or intellectual property office of n.z. 21 DEC 2m V RECC: ! - 258 - one or two hydrogen atoms may each be replaced by a Ci-3-alkyl group and/or the methylene group in position 3 of the pyrrolidino group may be substituted by a hydroxy or Ci_3-alkoxy group, in each case the methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be substituted by a hydroxy, hydroxy-Ci-3-alkyl, Ci-3-alkoxy, carboxy, Ci-3-alkoxycarbonyl, aminocarbonyl, Ci-3-alkylaminocarbonyl, di- (Ci-3-alkyl) -aminocarbonyl, phenyl-Ci-3-alkylamino or N-(Ci-3-alkyl)-phenyl-Ci-3-alkyl-amino group or may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (Ci-3-alkyl) , -N (phenyl) , -N (phenyl-Ci-3-alkyl) , -N (Ci-3-alkyl-carbonyl) , -N (Ci-4-alkox y-carbonyl), -N (benzoyl) or -N (phenyl-Ci-3-alkyl-carbonyl) group, wherein a methylene group linked to an imino-nitrogen atom of the cycloalkyleneimino group may be replaced by a carbonyl or sulphonyl group or in a 5- to 6-membered monocyclic cycloalkyleneimino group or a cycloalkyleneimino group fused to a phenyl group the two methylene groups linked to the imino-nitrogen atom may each be replaced by a carbonyl group, or R6 denotes a Ci-4-alkyl group which is terminally substituted by a carboxy, Ci-3-alkoxycarbonyl, aminocarbonyl, Ci-3-alkylaminocarbonyl or di-(Ci-3-alkyl)-aminocarbonyl group or by a 4- to 7-membered cycloalkyleneiminocarbonyl group, a group of formula intellectual property office of n.z. 2 1 DEC 200*1 RECEIVED _ - 259 - -N(R12)-CO-(CH2)p-Ri3 (IV), wherein R12 denotes a hydrogen atom, a Ci-3-alkyl, Cs-7-cycloalkyl, phenyl-Ci-3-alkyl or heteroaryl-Ci-3-alkyl group and p denotes one of the numbers 0, 1, 2 or 3 and R13 assumes the meanings of the abovementioned group R7, or, if p denotes one of the numbers 1, 2 or 3, it may also denote a hydrogen atom, a group of formula ~N(R14)~(CH2)q-(CO)r-R15 (V), wherein R14 denotes a hydrogen atom, a Ci_4-alkyl group, a Ci-3-alkylcarbonyl, phenylcarbonyl, phenyl-Ci-3-alkyl-carbonyl, heteroarylcarbonyl, heteroaryl-Ci-3-alkylcarbonyl, Ci-4-alkylsulphonyl, phenylsulphonyl, phenyl-Ci-3-alkyl- sulphonyl- heteroarylsulphonyl or heteroaryl-Ci-3-alkyl-sulphonyl group, q denotes one of the numbers 1, 2, 3 or 4, r denotes the number 1 or, if q is one of the numbers 2, 3 or 4, it may also denote the number 0 and Ris assumes the meanings of the abovementioned group R7, ~ ^ , intellectual property office a group of formula ^ 2 1 DEC 20m received tslixt'. ctual propertv s OF N.Z. 2 t DEC 200# RECEIVED - 260 --N(Ri6)-S02-Rl7 (V-I), wherein Ri6 denotes a hydrogen atom or a Ci-4-alkyl group optionally terminally substituted by a cyano, trifluoromethyl-carbonylamino or N- (Ci-3-alkyl)-trifluoromethyl—carbonyl-amino group and R17 denotes a Ci-3-alkyl group, an amino group substituted by a di-(Ci-3-alkyl)-amino-Ci-3-alkyi-carbonyl or di-(Ci-3-alkyl) -amino-Ci-3-alkyl-sulphonyl group and a di-(Ci-3-alkyl) -aminocarbonyl-Ci-3-alkyl group, wherein all the single-bonded or fused phenyl groups contained in the groups mentioned under R6 may be mono- or disubstituted by fluorine, chlorine or bromine - atoms, by Ci-3-alkyl, trif luoromethyl, hydroxy, Ci-3-alkoxy, carboxy, Ci-3-alkoxycarbonyl, aminocarbonyl, Ci_3-alkyl-aminocarbonyl, aminosulphonyl, Ci-3-alkyl-aminosulphonyl, nitro or cyano groups, wherein the substituents may be identical or different, or two adjacent hydrogen atoms of the phenyl groups may be replaced by a methylenedioxy group, and R5 denotes a hydrogen atom or a Ci-3-alkyl group, whilst by a heteroaryl group as mentioned above is meant a pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, furyl, thienyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl or triazolyl group optionally substituted in the carbon skeleton by a Ci-3-alkyl group wherein a hydrogen atom bound to a nitrogen atom may be replaced by a Ci-3-alkyl or - 261 - phenyl-Ci-3-alkyl group and wherein the 5-membered heteroaryl groups containing at least one imino group are bound via a carbon or nitrogen atom, a hydrogen atom bound to a nitrogen atom in the abovementioned groups may be replaced by a hydroxyl group, an acyl group, an allyloxycarbonyl group, a Ci-i6~alkoxycarbonyl group, a phenyl-Ci-6-alkoxylcarbonyl group, a C1-3-alkylsulphonyl-C2-4-alkoxycarbonyl, Ci-3-alkoxy-C2-4-alkoxy-C2-4_ alkoxycarbonyl or ReC0-0-(RfCRg)-0-C0 group where Re denotes a Ci-s-alkyl, Cs-7-cycloalkyl, phenyl or phenyl-Ci-3-alkyl group, Rf denotes a hydrogen atom, a Ci_3-alkyl, Cs-7-cycloalkyl or phenyl group and Rg denotes a hydrogen atom, a Ci_3-alkyl or ReC0-0-(RfCRh) -0 wherein Re and Rf are as herein before defined and Rh is a hydrogen atom or a C1-3 alkyl group, the carboxy groups contained in the abovementioned groups may each be substituted by a tert.butoxycarbonyl precursor group, some or all of the hydrogen atoms in the abovementioned alkyl and alkoxy groups or in the alkyl moieties contained in the above-defined groups of formula I may be replaced by fluorine atoms and a tautomer, diastereomer, enantiomer, or mixture thereof or a salt thereof.

3. An indolinone of general formula I according to claim 1, wherein X denotes an oxygen atom, 'nlellectual hhoperty office of n.z. ~ 1 MAR 2005 RECEIVED - 262 - Ri denotes a hydrogen atom, R2 denotes a carboxy group, a straight-chain or branched Ci-4-alkoxycarbonyl group or a phenoxycarbonyl group, a straight-chain or branched Ci_3-alkoxy-carbonyl group, which is terminally substituted in the alkyl moiety by a phenyl, carboxy, Ci-3-alkoxycarbonyl, aminocarbonyl, Ci-3-alkylaminocarbonyl or di-(Ci_3-alkyl)-aminocarbonyl group, a straight-chain or branched C2-3~alkoxy-carbonyl group which is terminally substituted in the alkyl moiety by a hydroxy, Ci-3-alkoxy, amino, Ci-3-alkylamino or di-(Ci-3-alkyl)-amino group, an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2 position of the ethyl group by a hydroxy or Ci-3-alkoxy group or, if R4 does not denote an aminosulphonyl-phenyl or N- (Ci-5-alkyl) -Ci-3-alkylaminocarbonyl-phenyl group, it may also denote a di- (Ci-2-alkyl) -aminocarbonyl group, R3 denotes a Ci-4-alkyl group or a phenyl group which may be substituted by a fluorine, chlorine or bromine atom, by a trifluoromethyl, Ci-3-alkyl, hydroxy or Ci-3-alkoxy group, R4 denotes a Cs-6-cycloalkyl group, wherein the methylene group in position 4 of the cyclohexyl group may be substituted by an amino, Ci-3-alkylamino or di-(Ci-3-alkyl)-amino group or replaced by an -NH or -N (Ci-3-alkyl) group, intellectual PROPERTY office of N.Z 2 1 DEC 2004 RECEIVED - 263 - a phenyl group, a phenyl group disubstituted by Ci-3-alkyl, Ci-3-alkoxy or nitro groups, wherein the substituents may be identical or different, or a phenyl group substituted by the group R6, which may additionally be substituted by a fluorine, chlorine or bromine atom or by an amino or nitro group, wherein R6 denotes a fluorine, chlorine or bromine atom, a Ci-3-alkyl, Ci-3-alkoxy, nitro, amino or Cs-6-cycloalkyl group, a pyrrolyl, pyrazolyl, imidazolyl, triazolyl or tetrazolyl group bound via a carbon atom, wherein the abovementioned heteroaromatic groups in the carbon skeleton may be substituted by a Ci-3-alkyl group or a hydrogen atom bound to a nitrogen atom may be replaced by a Ci-3-alkyl or phenyl-Ci-3-alkyl group, the group of formula a carboxy, Ci-4-alkoxycarbonyl, phenyl-Ci-3-alkylamino-carbonyl or C5-7-cycloalkyl-carbonyl group, a 5 or 6-membered cycloalkyleneimino group, wherein the methylene group in position 4 of the piperidino group may be replaced by an oxygen or sulphur atom, by an -NH or -N (Ci-3-alkyl) group, CH' intellectual property office of n.z. 21 dec 2m RECEIVED - 264 - an unbranched Ci-3-alkyl group terminally substituted by the group R7, wherein R7 denotes a Cs-7-cycloalkyl group, wherein in a 5 or 6-membered cycloalkyl group a —(CH2) 2 group may be replaced by a -CO-NH group, a —(CH2) 3 group may be replaced by an -NH-CO-NH- or a —(CH2) 4 group may be replaced by an -NH-CO-NH-CO group, whilst in each case a hydrogen atom bound to a nitrogen atom may be replaced by a Ci-3-alkyl group, a phenyl or pyridinyl group or a pyrrolyl, pyrazolyl, imidazolyl or triazolyl group bound via a carbon or nitrogen atom, wherein the abovementioned heteroaromatic groups in the carbon skeleton may be substituted by a Ci-3-alkyl group or a hydrogen atom bound to a nitrogen atom may be replaced by a Ci-3-alkyl group, a hydroxy or Ci-3-alkoxy group, an amino, Ci-6-alkylamino, di- (Ci-6-alkyl) -amino, phenylamino, N-phenyl-Ci-3-alkylamino, phenyl-Ci-3-alkylamino or N-(Ci-3-alkyl)-phenyl-Ci-3-alkylamino group, a co-hydroxy-C2-3-alkyl-amino, N- (Ci-3-alkyl) -

4. An indolinone of general formula I according to claim 1, wherein X denotes an oxygen atom, Ri and R5 each denote a hydrogen atom, R2 denotes a methoxycarbonyl, ethoxycarbonyl or aminocarbonyl group, R3 denotes a phenyl group and R4 denotes a phenyl group monosubstituted by the group R6, wherein R6 denotes an N-methyl-imidazol-2-yl group, INTELLECTUAL PROPERTY OFFICE OF N.Z. 21 DEC 2DQ"i i P" « \ / p 0 - 270 - an unbranched Ci-3-alkyl group which is terminally substituted by a Ci-4-alkylamino, di-(Cx-4-alkyl)-amino, piperidino or 2,6-dimethyl-piperidino group, a group of formula -N(R12)-CO-(CH2)p-Ri3 (IV), wherein R12 denotes a Ci_3-alkyl group, p denotes one of the numbers 1 or 2 and R13 denotes a di-(Ci-3-alkyl)-amino group, or a group of formula -N(Ri4)-(CH2)q-(CO)r-Ri5 (V), wherein R14 denotes a Ci_3-alkyl-carbonyl or Ci-3-alkylsulphonyl group, q denotes one of the numbers 1, 2 or 3, r denotes the number 1 or, if q is one of the numbers 2 or 3, r may also denote the number 0 and Ris denotes a di-(Ci_3-alkyl)-amino group, a tautomer, diastereomer, enantiomer, or a mixture thereof or a salt thereof. imtfiiFCTUAL property UbHcTf of n.z. 2 1 DEC imh RECE(Vr:£ - 271 -

5. A substituted indolinone of general formula I according to claim 1 selected from: (a) 3-Z-[ 1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone, (b) 3—Z—[ (1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-carbamoyl-2-indolinone, (c) 3 —Z—[ 1-(4-(piperidin-l-yl-methyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (d) 3-Z-[ 1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone, (e) 3-Z-[ 1-(4-((2,6-dimethyl-piperidin-l-yl)-methyl)-anilino) -1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone, (f) 3—Z—[ 1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-anilino) -1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone, (g) 3-Z-[ 1-(4-(N-(3-dimethylamino-propyl)-N-acetyl-amino)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone, (h) 3—Z—[ 1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone, (i) 3—Z—[ 1-(4-(dimethylaminomethyl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (j) 3-Z-[ 1-(4-(N-acetyl-N-dimethylaminocarbonylmethyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, intellectual PROPERTY OFFICE OF N.Z. 2 1 DEC 2004 - 272 - (k) 3—Z —[ 1-(4-ethylaminomethyl-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (1) 3—Z—[ 1-(4-(l-methyl-imidazol-2-yl)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (m) 3-Z-[ 1-(4-(N-dimethylaminomethylcarbonyl-N-methyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (n) 3-Z-[ 1-(4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2- , indolinone, (o) 3—Z—[ 1-(4-(N-(3-dimethylamino-propyl)-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (p) 3—Z—[ 1-(4-(N-dimethylaminocarbonylmethyl-N-methylsulphonyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (q) 3—Z —[ 1-(4-(N-((2-dimethylamino-ethyl)-carbonyl)-N-methyl-amino) -anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, (r) 3 — Z —[ 1-(4-(N-(2-dimethylamino-ethyl)-N-acetyl-amino)-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone and (s) 3—Z—[ 1-(4-methylaminomethyl-anilino)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, and (t) 3-Z-[ 1-(4-(N-((4-methyl-piperazin-l-yl)-methylcarbonyl)-N-methyl-amino)aniline)-1-phenyl-methylene] -6- methoxycarbonyl-2-indolinone, INTELLECTUAL PROPERTY OFFICE OF N.Z. 2 1 DEC 2004 RECEIVED - 273 - the tautomers, the mixtures and the salts thereof.

6. 3-Z-[ 1-(4-(N-((4-methyl-piperazin-l-yl)-methylcarbonyl)-N-methyl-amino)aniline)-1-phenyl-methylene] -6-methoxycarbonyl-2-indolinone, a tautomer or salt thereof.

7. A physiologically acceptable salt of a compound according to any one of claims 1 to 6.

8. A pharmaceutical composition containing a compound according to at any one of claims 1 to 6 or a salt according to claim 7 optionally together with one or more inert carriers and/or diluents.

9. Use of a compound according to at any one of claims 1 to 6 or a salt according to claim 7 for preparing a . pharmaceutical composition which is suitable for treating excessive or anomalous cell proliferation.

10. Process for preparing a pharmaceutical composition according to claim 8, wherein a compound according to at any one of claims 1 to 6 or a salt according to claim 7 is incorporated in one or more inert carriers and/or diluents by a non-chemical method.

11. Process for preparing a compound according to claims 1 to 7, wherein a. a compound of general formula INTELLECTUAL PROPERTY OFFICE OF n.z. 2 1 DEC 200** - 274 - (VII) wherein X and R3 are defined as in claims 1 to 6, R2' has the meanings given for R2 in claims 1 to 6, Ris denotes a hydrogen atom or a protecting group for the nitrogen atom of the lactam group, wherein one of the groups R2' and Ris may also denote a bond to a solid phase optionally formed via a spacer and the other one of the groups R2' and Ris has the abovementioned meanings,• and Zi denotes a halogen atom, a hydroxy, alkoxy or aryl-alkoxy group, is reacted with an amine of general formula wherein R4 and R5 are defined as in claims 1 to 6, and subsequently, if required, any protecting group used for the nitrogen atom of the lactam group is cleaved or a compound thus obtained is cleaved from a solid phase, or b. in order to prepare a compound of general formula I wherein R2 has the meanings given in claims 1 to 6, with the H - N (VIII), exception of the carboxy group, INTELLECTUAL property office of N.Z. 2 1 DEC 200* - 275 - a compound of general formula HOOC (IX) , wherein Ri and R3 to R5 are defined as in claims 1 to 6, or a reactive derivative thereof, is reacted with a compound of general formula H - R19 (X), wherein R19 denotes a Ci-6-alkanol, a C4-7_cycloalkanol or an aromatic alcohol, a Ci-6-alkanol which is terminally substituted in the alkyl moiety by a phenyl, heteroaryl, carboxy, Ci-3-alkoxy-carbonyl, aminocarbonyl, Ci_3-alkylamino-carbonyl or di- (Ci-3-alkyl) -aminocarbonyl group, a C2-6-alkanol which is terminally substituted in the alkyl moiety by a chlorine atom or a hydroxy, Ci-3-alkoxy, amino, Ci-3-alkylamino or di-(Ci-3-alkyl)-amino group, an amino or methylamino group, an ethylamino group optionally substituted in the 2 position of the ethyl group by a hydroxy or Ci-3-alkoxy group or a di- (Ci-2-alkyl) -amino group, or INTELLECTUAL PROPERTY OFFICE OF N.Z. 2 1 DEC 2004 I received s - 276 - INTEi ;„CGTUAt PROPERTY OFRCE OF N.Z 21 CSS 2004 _EECEived c. in order to prepare a compound of general formula I, wherein R4 denotes a Ci-4-alkyl group substituted by the group R7, wherein R7 denotes an amino, Ci-7-alkylamino, di- (Ci-7-alkyl) -amino, phenylamino, N-phenyl-Ci-3-alkyl-amino, phenyl-Ci-3-alkylamino, N- (Ci-3-alkyl) -phenyl-Ci-3-alkylamino or di- (phenyl-Ci-3-alkyl) -amino group, a a>-hydroxy-C2-3-alkyl-amino, N- (Ci-3-alkyl) -o-hydroxy-C2-3~alkyl-amino, di- (co-hydroxy-C2-3-alkyl) -amino, di- (co- (Ci-3-alkoxy) -C2-3-alkyl) -amino or N-(dioxolan-2-yl)-Ci-3-alkyl-amino group, a Ci_3-alkylcarbonylamino-C2-3-alkyl-amino or Ci_3-alkylcarbonylamino-C2-3-alkyl-N- (Ci-3-alkyl) -amino group, a Ci-3-alkylsulphonylamino, N- (Ci_3-alkyl) -Ci-3-alkylsulphonylamino, Ci-3-alkylsulphonylamino-C2-3~alkyl-amino or Ci_3-alkylsulphonylamino-C2-3-alkyl-N- (Ci-3-alkyl) -amino group, a group of formula "N (R10) - (CH2) ja- (CO) 0-Rn (III), wherein Rio denotes a hydrogen atom, a Ci_3-alkyl group, a Ci-3-alkylcarbonyl, arylcarbonyl, phenyl-Ci-3-alkyl- - 277 - 2 I OK 2304 BECEIvf :: carbonyl, Ci-3-alkylsulphonyl, arylsulphonyl or phe-nyl-Ci-3-alkylsulphonyl group, m denotes one of the numbers 1, 2, 3 or 4, o denotes the number 1 and R11 denotes an amino, Ci-4-alkylamino, di- (Ci-4-alkyl) -amino, phenylamino, N-(Ci-4-alkyl)-phenylamino, benzylamino, N-(Ci-4-alkyl)-benzylamino, Ci_4-alkoxy or Ci-3-alkoxy-Ci-3-alkoxy group, a di-(Ci-4-alkyl)-amino-Ci-3-alkylamino group optionally substituted in the 1 position by a Ci-3-alkyl group, or a 4- to 7-membered cycloalkyleneimino group, wherein the cycloalkylene moiety may be fused to a phenyl ring or in each case the methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (Ci-3-alkyl) , -N (phenyl), -N(Ci-3-alk yl-carbonyl) or -N(benzoyl) group, a C4-7-cycloalkylamino, C4-7-cycloalkyl-Ci_3-alkylamino or C4_7-cycloalkenylamino group wherein position 1 of the ring is not involved in the double bond and wherein the abovementioned groups may each additionally be substituted at the amino-nitrogen atom by a Cs-7-cycloalkyl, C2-4~alkenyl or Ci-4-alkyl group, or a 4- to 7-membered cycloalkyleneimino group, wherein the cycloalkylene moiety may be fused to a phenyl group or to an oxazolo, imidazolo, thiazolo, pyridino, pyrazino or pyrimidino group optionally INTELLECTUAL PROPERTY QPRCg OF N.Z. 2 I DEC 2004 ~ 278 ~ RECEIVED substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, Ci_3-alkyl, Ci-3-alkoxy or amino group, and/or one or two hydrogen atoms may each be replaced by a Ci-3-alkyl, C5-7-cycloalkyl or phenyl group and/or the methylene group in the 3 position of a 5-membered cycloalkyleneimino group may be substituted by a hydroxy, hydroxy-Ci_3-alkyl, Ci-3-alkoxy or Ci-3-alkoxy-Ci_3-alkyl group, in each case the methylene group in the 3 or 4 position of a 6-=- or 7-membered cycloalkyleneimino group may be substituted by a hydroxy, hydroxy-Ci-3-alkyl, Ci-3-alkoxy, Ci-3-alkoxy-Ci-3-alkyl, Ci-4-alkoxycarbonyl, aminocarbonyl, Ci-3-alkylaminocarbonyl, di- (Ci-3-alkyl) -aminocarbonyl, phenyl-Ci_3-alkylamino or N-(Ci-3-alkyl)-phenyl-Ci-3-alkylamino group or may be replaced by an oxygen or sulphur atom, by a sulphinyl, sulphonyl, -NH, -N (Ci-3-alkyl-) , -N (phenyl), -N (phenyl-Ci-3-alkyl-), -N (Ci-3-alkyl-carbonyl-) , -N (Ci-4-alkoxy-carbonyl-) , -N (benzoyl-) or -N (phenyl-Ci-3-alkyl-carbonyl-) group, wherein a methylene group linked to an imino-nitrogen atom of the cycloalkyleneimino group may be replaced by a carbonyl or sulphonyl group or in a 5- to 7-membered monocyclic cycloalkyleneimino group or a cycloalkyleneimino group fused to a phenyl group the two methylene groups linked to the imino-nitrogen atom may each be replaced by a carbonyl group, INTELLECTUAL PROPERTY OPF1GE Of N.Z. 21 DEC 2004 RECEIVED - 279 - a compound of general formula (XI) , wherein R3, R5 and X are defined as in claims 1 to 6, R21 has the meanings given for R2 in claims 1 to 6, Rig denotes a hydrogen atom or a protecting group for the nitrogen atom of the lactam group, wherein one of the groups R2' and Ris may also denote a bond to a solid phase optionally formed via a spacer and the other one of the groups R2' and Ris has the abovementioned meanings, A denotes a Ci-4-alkyl group and Z2 denotes a leaving group, is reacted with an amine of general formula H—R7, (XII), wherein Rt has the meanings given for R7 hereinbefore, and subsequently, if necessary, any protecting group used for .the nitrogen atom of the lactam group is cleaved, or a compound thus obtained is cleaved from a solid phase, and subsequently, if desired, a compound of general formula I thus obtained which contains an alkoxycarbonyl group is converted by hydrolysis into a corresponding carboxy compound, or - 280 - INTELLECTUAL PROPERTY OFFIC OF N.Z. 2 1 DEC 2Q04 RECEIVFD a compound of general formula I thus obtained which contains an amino or alkylamino group is converted by reductive alkylation into a corresponding alkylamino or dialkylamino compound, or a compound of general formula I thus obtained which contains an amino or alkylamino group is converted by acylation or sulphonation into a corresponding acyl or sulphonyl compound or a compound of general formula I thus obtained which contains a carboxy group is converted by esterification or amidation into a corresponding ester or aminocarbonyl compound or a compound of general formula I thus obtained which contains a cycloalkyleneimino group wherein a methylene group is replaced by a sulphur atom is converted by oxidation into a corresponding sulphinyl or sulphonyl compound, or a compound of general formula I thus obtained which contains a nitro group is converted by reduction into a corresponding amino compound, or a compound of general formula I thus obtained wherein R4 denotes a phenyl group substituted by an amino, alkylamino, aminoalkyl or N-alkyl-amino group is converted, by reaction with a corresponding cyanate, isocyanate or carbamoyl halide, into a corresponding urea compound of general formula I or a compound of general formula I thus obtained wherein R4 denotes a phenyl group substituted by an amino, alkylamino, aminoalkyl or N-alkyl-amino group is converted, by reaction with a corresponding compound which transfers the amidino group or by reaction with a corresponding nitrile, into a corresponding guanidino compound of general formula I, or intellectual property off of N.Z. 2 I DEC 2004 RECEivro - 281 - / if necessary any protecting group used during the reactions to protect reactive groups is cleaved or subsequently, if desired, a compound of general formula I thus obtained is resolved into the stereoisomers thereof or a compound of general formula I thus obtained is converted into the salts thereof, particularly, for pharmaceutical use, into the physiologically acceptable salts thereof with an inorganic or organic acid or base.

12. An indolinone compound or salt according to any one of claims 1. to 7, substantially as herein described.

13. An indolinone compound or salt according to any one of claims 1 to 7, substantially as herein described with reference to any one of Examplesl to 12.

14. A pharmaceutical composition according to claim 8, substantially as herein described.

15. A pharmaceutical composition according to claim 8, substantially as herein described with reference to any one of Examples 1 to 19.

16. Use according to claim 9, substantially as herein described.

17. Use according to claim 9, substantially as herein described with reference to any one of Examples 1 to 19.

18. Process according to claim 10 or claim 11, substantially as herein described. 518489 - 282 -

19. Process according to claim 10 or claim 11, substantially as herein described with reference to any one of Examples 1 to 19. BOEHRINQERINGELHEIM PHARMAI GM&H5 CO. KG *W By it^Xkttorneys BALDWINS INTELLECTUAL PROPERTY OFFICE OF n.z. 2 1 DEC 200*1 RECEIVE 0 I