DE10252969A1 - New 3-aminomethylene-indoline-2-(thi)one derivatives, are kinase inhibitors useful for treating proliferative diseases e.g. tumors, rheumatoid arthritis, neovascular glaucoma and arteriosclerosis - Google Patents

Abstract

3-(1-Heterocyclyl-1-(N-substituted amino)-methylene)-indoline-2-(thi)one derivatives (I) are new. 3-(1-Heterocyclyl-1-(N-substituted amino)-methylene)-indoline-2-(thi)one derivatives of formula (I) and their tautomers, enantiomers, diastereomers (or mixtures), prodrugs and salts are new. X = O or S; R1 = H or prodrug residue (e.g. COT or COOU); T = 1-3C alkyl; U = 1-4C alkyl; R2 = H, F, Cl, Br, CN, NO2, COOH, (1-6C) alkoxycarbonyl, (3-6C) cycloalkoxycarbonyl, COOAr or OCOCH2CH=CH2 (optionally substituted (os)), COOU terminally substituted by Het, Ph, COOH, COOT, CONH2, CONHT or CONT2, (2-6C) alkoxycarbonyl terminally substituted by Cl, OH, OT, NHT or NT2; or CONH2, CONHU or CONU2 (where alkyl moieties (other than Me) are os); R3 = e.g. (i) 6-membered heteroaryl containing 1-3 N or 5-membered heteroaryl containing one NH, N(T), N(T-COOH), N(T-Ph), O or S and optionally 1 or 2 N, both optionally fused to a phenyl ring (os), provided that bonding is via a C-atom of the heterocyclic part or (ii) a 5- or 6-membered cyclic oxime ether bonded via the C-atom adjacent to the N; R4 = (i) 3-7C cycloalkyl (optionally with CH2 in the 4-position of 6-7C cycloalkyl substituted); (ii) phenyl substituted in the 3- or 4-position by R6 and additionally os by 1 or 2 of e.g. halo or 1-5C alkyl, or (iii) 1-(R22)-2-(CONR23R24)-pyrrol-4-yl; R6 = H, halo, CN, NO2, NH2, 1-5C alkyl, 3-7C cycloalkyl, CF3, Ph or Het, tetrazolyl (os by T), 2-pyrrolidon-1-yl (optionally having CH2 adjacent to CO replaced by O, NH or NT), 2,4-dioxo-imidazolidin-5-ylidene-methyl (os), (CH2)n-COR8, (CH2)o-CONR9R10, T-R7, N(R15)-CO-(CH2)s-R16, N(R17)-SO2R18, amino substituted by CO-T-NT2 or SO2-T-NT2 and by T-CO-NT2, A-(CH2)t-R19 or SO2N(R20)-(CH2)u-R21; R8 = OH, OU or 2,5-dihydro-pyrrol-1-yl, 5-7 membered cycloalkyleneimino (os in the 3- or 4-position in the case of 5-7 membered rings, and optionally having the CH2 in the 4-position of 6- or 7-membered rings replaced by O, S, SO, SO2, NH, N(allyl) or NT), os by 1 or 2 T, or 3-7C cycloalkyl (os in the 3- or 4-position in the case of 5-7 membered rings; and optionally with CH2 in the 4-position of 6-7C cycloalkyl replaced by NH, N(allyl) or NT), all singly bonded or fused phenyl rings in R6 are os by 1 or 2 of halo, 1-5C alkyl, CF3, OH, OT, COOH, COOT, CONH2, CONHT, CONT2, SO2NH2, SO2NHT, SO2NT2, NHSO2T, NO2 or CN or by one OCH2O; n = 0-2; R9 = H, allyl, U (os) or 2-4C alkyl terminally substituted by OH or OT; R10 = H or T; 2-3C alkyl terminally substituted by OH, OT, NHT or NT2; or 3-7C cycloalkyl (optionally having one CH2 replaced); o = 0-2; R7 = e.g. 3-7C cycloalkyl (os), Ar, Het, triazolyl, OH, OT, NH2, mono- or di-(1-7C alkyl)-amino or N-(1-7C alkyl)-allylamino; R15 = H, allyl, 1-6C alkyl, 3-7C cycloalkyl or pyridinyl, T terminally substituted by Ph, Het, CF2, CONH2, CONHU, CONU2, COT, SO2NHT or SO2NT2; or 2-3C alkyl terminally substituted by OH, OT, NH2, NHT, allylamino, NT2, NHSO2T or N(T)SO2T; s = 0-3; R16 = COOH or as for R7, or may also be H if s = 1-3; R17 = H, allyl, U or CH2CN; or 2-4C alkyl terminally substituted by CN, NH2, NHT, NT2, NHCOCF3 or NTCOCF3; R18 = T, Ph or pyridyl; A = O, S, SO or SO2; R19 = H, OH, OT, Ar, Het or NH2; or 4-7 membered cycloalkyleneimino (os); t = 2 or 3, or may also be 1 if R19 = H, Ar or Het, or may also be 0 if A = SO2; R20 = H, allyl or T; R21 = H, OH, NH2, NHT or NT2; u = 2-4, or may also be 1 if R21 = H; R22 = T; R23 = H or allyl, U (os by CN, COOH, Ph or pyridyl) or 2-4C alkyl terminally substituted by OH or OT; R24 = H or T, 2-3C alkyl terminally substituted by OH, OT, NHT or NT2 or 3-7C cycloalkyl (optionally having one CH2 replaced), or NR23R24 = 2,5-dihydropyrrol-1-yl or 5-7 membered cycloalkyleneimino (os); R5 = H or T; Ar = phenyl or naphthyl (both os); Het = 6-membered heteroaryl (containing 1-3 N) or 5-membered heteroaryl (containing one NH, N(T), N(T-Ph), O or S and optionally 1 or 2 N), both optionally fused to a phenyl ring (os by 1 or 2 T, NH2, NHT or NT2), where bonding is via a C- or N-atom of the heterocyclic part or via a C-atom of

Description

deren Tautomere, deren Diastereomere, deren Enantiomere, deren Gemische, deren Prodrugs und deren Salze, insbesondere deren physiologisch verträgliche Salze, welche wertvolle Eigenschaften aufweisen.The present invention relates to new heterocyclically substituted indolinones of the general formula

their tautomers, their diastereomers, their enantiomers, their mixtures, their prodrugs and their salts, in particular their physiologically tolerable salts, which have valuable properties.

The above general connections Formula I have valuable pharmacological properties, in particular an inhibitory effect on various kinases, especially on Receptor tyrosine kinases such as VEGFR1, VEGFR2, VEGFR3, PDGFRα, PDGFRβ, 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 its specific cyclins (A, B1, B2, C, D1, D2, D3, E, F, G1, G2, H, I and K) and viral cyclin (see L. Mengtao in J. Virology 71 (3), 1984-1991 (1997)), as well as on the proliferation of cultivated human cells, especially those of endothelial cells, e.g. in angiogenesis, however also on the proliferation of other cells, especially tumor cells.

Object of the present invention are thus the above compounds of general formula I, which have valuable pharmacological properties that pharmacologically active compounds containing drugs, their use and methods of making them.

in der die an ein Stickstoffatom gebundenen Wasserstoffatome unabhängig voneinander jeweils durch eine C_1-3-Alkylgruppe ersetzt sein können,
eine Gruppe der Formel -(CH₂)_n-CO-R₈ in der
R₈ eine Hydroxy- oder C_1-4-Alkoxygruppe,
eine 5- bis 7-gliedrige Cycloalkyleniminogruppe,
wobei die Methylengruppe in Position 3 oder 4 einer 5-, 6- oder 7-gliedrigen Cycloalkyleniminogruppe durch eine Amino-, C_1-3-Alkylamino- oder Di-(C_1-3-alkyl)-aminogruppe substituiert sein kann
oder die Methylengruppe in Position 4 einer 6- oder 7-gliedrigen Cycloalkyleniminogruppe durch ein Sauerstoffatom, ein Schwefelatom, eine Sulfinyl- oder Sulfonylgruppe, eine -NH-, -N(Allyl)- oder -N(C_1-3-Alkyl)- Gruppe ersetzt sein kann
und wobei in den genannten cyclischen Gruppen ein oder zwei Wasserstoffatome durch eine C_1-3-Alkylgruppe ersetzt sein können,
eine 2,5-Dihydropyrrol-1-yl-gruppe oder
eine C_3-7-Cycloalkyl-gruppe,
wobei die Methylengruppe in Position 3 oder 4 des 5-, 6- oder 7-gliedrigen Cycloalkylteils durch eine Amino-, C_1-3-Alkylamino- oder Di-(C_1-3-alkyl)-aminogruppe substituiert oder
die Methylengruppe in Position 4 des 6- oder 7-gliedrigen Cycloalkylteils durch eine -NH-, -N(Allyl)- oder -N(C_1-3-Alkyl)- Gruppe ersetzt sein kann,
und n eine der Zahlen 0, 1 oder 2 bedeuten,
eine Gruppe der Formel -(CH₂)_o-CO-NR₉R₁₀, in der
R₉ ein Wasserstoffatom,
eine Allylgruppe,
eine gegebenenfalls durch eine Cyano-, Carboxy-, Phenyl- oder Pyridylgruppe substituierte C_1-4-Alkylgruppe oder
eine terminal durch eine Hydroxy- oder C_1-3-Alkoxygruppe substituierte C_2-4-Alkylgruppe,
R₁₀ ein Wasserstoffatom,
eine C_1-3-Alkylgruppe,
eine terminal durch eine Hydroxy-, C_1-3-Alkoxy-, C_1-3-Alkylamino- oder Di-(C_1-3-alkyl)-aminogruppe substituierte C_2-3-Alkylgruppe oder
eine 3- bis 7-gliedrige Cycloalkylgruppe,
in der eine Methylengruppe durch ein Sauerstoffatom oder eine -NH- oder -N(C_1-3-Alkyl)- Gruppe ersetzt sein kann und unabhängig davon eine Methylengruppe durch eine Carbonylgruppe ersetzt sein kann,
und o eine der Zahlen 0, 1 oder 2 bedeuten,
eine durch die Gruppe R₇ substituierte C_1-3-Alkylgruppe, wobei
R₇ eine C_3-7-Cycloalkylgruppe,
wobei eine der Methylengruppen durch eine Amino-, C_1-3-Alkylamino- oder Di-(C_1-3-alkyl)-aminogruppe substituiert oder
die Methylengruppe in Position 3 oder 4 einer 5-, 6- oder 7-gliedrigen Cycloalkylgruppe durch eine -NH-, -N(Allyl)- oder -N(C_1-3-Alkyl)-Gruppe ersetzt sein kann oder
in einer 5- bis 7-gliedrigen Cycloalkylgruppe eine -(CH₂)₂-Gruppe durch eine -CO-NH-Gruppe ersetzt sein kann, eine -(CH₂)₃-Gruppe durch eine -NH-CO-NH- oder -CO-NH-CO-Gruppe ersetzt sein kann oder eine -(CH₂)₄-Gruppe durch eine -NH-CO-NH-CO-Gruppe ersetzt sein kann, wobei jeweils ein an ein Stickstoffatom gebundenes Wasserstoffatom durch eine C_1-3-Alkylgruppe ersetzt sein kann,
eine Aryl- oder Heteroarylgruppe,
eine Triazolylgruppe,
eine Hydroxy- oder C_1-3-Alkoxygruppe, eine Amino-, C_1-7-Alkylamino-, Di-(C_1-7-alkyl)-amino-, N-(C_1-7-Alkyl)-allylamino-, Phenylamino-, N-Phenyl-C_1-3-alkyl-amino-, Phenyl-C_1-3-alkylamino-, N-(C_1-3-Alkyl)-phenyl-C_1-3-alkylamino- oder Di-(phenyl-C_1-3-alkyl)-aminogruppe,
eine Allylaminogruppe, in der ein oder zwei vinylische Wasserstoffatome jeweils durch eine Methylgruppe ersetzt sein können,
eine ω-Hydroxy-C_2-3-alkyl-amino-, N-(C_1-3-Alkyl)-ω-hydroxy-C_2-3-alkyl-amino-, Di-(ω-hydroxy-C_{2- 3}-alkyl)-amino-, ω-(C_1-3-Alkoxy)-C_2-3-alkyl-amino-N-(C_1-3-Alkyl)- [ω-(C_1-3-alkoxy)-C_2-3-alkyl)-amino-, Di-[ω-(C_1-3-alkoxy)-C_2-3-alkyl]-amino- oder N-(Dioxolan-2-yl)-C_1-3-alkyl-aminogruppe,
eine C_1-3-Alkylcarbonylamino-C_2-3-alkyl-amino- oder C_1-3-Alkylcarbonylamino-C_2-3-alkyl-N-(C_1-3-alkyl)-aminogruppe,
eine Pyridylaminogruppe,
eine C_1-3-Alkylsulfonylamino-, N-(C_1-3-Alkyl)-C_1-3-alkylsulfonylamino-, C_1-3-Alkylsulfonylamino-C_2-3-alkyl-amino- oder C_1-3-Alkylsulfonylamino-C_2-3-alkyl-N-(C_1-3-alkyl)-aminogruppe,
eine Hydroxycarbonyl-C_1-3-alkylamino- oder N-(C_1-3-Alkyl)-hydroxycarbonyl-C_1-3-alkyl-aminogruppe,
eine Guanidinogruppe, in der ein oder zwei Wasserstoffatome jeweils durch eine C_1-3-Alkylgruppe ersetzt sein können,
eine 2-Pyrrolidon-1-yl-gruppe, in der die der Carbonylgruppe benachbarte Methylengruppe durch ein Sauerstoffatom oder durch eine -NH- oder -N(C_1-3-Alkyl)-Gruppe ersetzt sein kann,
eine Gruppe der Formel -N(R₁₁)-CO-(CH₂)_p-R₁₂, in der
R₁₁ ein Wasserstoffatom oder eine Allyl-, C_1-3-Alkyl-, C_1-3-Alkyl-amino-C_2-3-alkyl- oder Di-(C_1-3-alkyl)-amino-C_2-3-alkylgruppe,
p eine der Zahlen 0, 1, 2 oder 3 und
R₁₂ eine Amino-, C_1-3-Alkylamino-, Allylamino-, Di-allyl-amino-, Di-(C_1-4-alkyl)-amino-, Phenylamino-, N-(C_1-4-Alkyl)-phenylamino-, Benzylamino-, N-(C_1-4-Alkyl)-benzylamino-, C_1-4-Alkoxy- oder 2,5-Dihydropyrrol-1-yl-gruppe oder
eine 4- bis 7-gliedrige Cycloalkyleniminogruppe,
wobei jeweils die Methylengruppe in Position 4 einer 6- oder 7-gliedrigen Cycloalkyleniminogruppe durch ein Sauerstoff oder Schwefelatom, durch eine Sulfinyl-, Sulfonyl-, -NH-, -N(C_1-3-Alkyl)-, -N(Allyl)-, -N(Phenyl)-, -N(C_1-3-Alkyl-carbonyl)- oder -N(Benzoyl)-Gruppe ersetzt sein kann,
oder, sofern n eine der Zahlen 1, 2 oder 3 darstellt, auch ein Wasserstoffatom bedeuten,
eine Gruppe der Formel -N(R₁₃)-(CH₂)_q-(CO)_r-R₁₄ in der
R₁₃ ein Wasserstoffatom oder eine C_1-3-Alkyl-, Allyl-, C_1-3-Alkyl-carbonyl-, Arylcarbonyl-, Pyridylcarbonyl-, Phenyl-C_1-3-alkyl-carbonyl-, C_1-3-Alkylsulfonyl-, Arylsulfonyl- oder Phenyl-C_1-3-alkylsulfonylgruppe,
q eine der Zahlen 1, 2, 3 oder 4,
r die Zahl 1 oder, sofern q eine der Zahlen 2, 3 oder 4 ist, auch die Zahl 0 und
R₁₄ eine Hydroxy-, Amino-, C_1-4-Alkylamino-, Di-(C_1-4-alkyl)-amino-, Phenylamino-, N-(C_1-4-Alkyl)-phenylamino-, Benzylamino-, N-(C_1-4-Alkyl)-benzylamino-, C_1-4-Alkoxy- oder C_1-3-Alkoxy-C_1-3-alkoxygruppe,
eine in 1-Position gegebenenfalls durch eine C_1-3-Alkylgruppe substituierte Di-(C_1-4-alkyl)-amino-C_1-3-alkylaminogruppe oder
eine 4- bis 7-gliedrige Cycloalkyleniminogruppe,
wobei der Cycloalkylenteil mit einem Phenylring kondensiert sein kann oder
jeweils die Methylengruppe in Position 4 einer 6- oder 7-gliedrigen Cycloalkyleniminogruppe durch ein Sauerstoff oder Schwefelatom, durch eine Sulfinyl-, Sulfonyl-, -NH-, -N(C_1-3-Alkyl)-, -N(Phenyl)-, -N(C_1-3-Alkyl-carbonyl)- oder -N(Benzoyl)-Gruppe ersetzt sein kann, bedeuten,
eine C_4-7-Cycloalkylamino-, C_4-7-Cycloalkyl-C_1-3-alkylamino- oder C_4-7-Cycloalkenylaminogruppe, in der die Position 1 des Rings nicht an der Doppelbindung beteiligt ist und wobei die vorstehend genannten Gruppen jeweils zusätzlich am Aminstickstoffatom durch eine C_{5 -7}-Cycloalkyl-, C_{2 -4}-Alkenyloder C_1-4-Alkylgruppe substituiert sein können,
eine 2,5-Dihydro-pyrrol-1-yl-gruppe oder
eine 4- bis 7-gliedrige Cycloalkyleniminogruppe, in der der Cycloalkylenteil mit einer Phenylgruppe oder mit einer gegebenenfalls durch ein Fluor-, Chlor-, Brom- oder Iodatom, durch eine Nitro-, C_1-3-Alkyl-, C_1-3-Alkoxy- oder Aminogruppe substituierten Oxazolo-, Imidazolo-, Thiazolo-, Pyridino-, Pyrazino- oder Pyrimidinogruppe kondensiert sein kann oder/und
ein oder zwei Wasserstoffatome jeweils durch eine C_1-3-Alkyl-, C_3-7-Cycloalkyl-, Hydroxy-, C_1-3-Alkoxy-, Hydroxy-C_1-3-alkyl-, C_1-3-Alkoxy-C_1-3-alkyl- oder Phenylgruppe ersetzt sein können oder/und
die Methylengruppe in Position 3 einer 5-gliedrigen Cycloalkyleniminogruppe durch eine Hydroxy-, Hydroxy-C_1-3-alkyl-, C_1-3-Alkoxy- oder C_1-3-Alkoxy-C_1-3-alkylgruppe substituiert sein kann,
jeweils die Methylengruppe in Position 3 oder 4 einer 6- oder 7-gliedrigen Cycloalkyleniminogruppe durch eine Hydroxy-, Hydroxy-C_1-3-alkyl-, C_1-3-Alkoxy-, C_1-3-Alkoxy-C_1-3-alkyl-, Carboxy-, C_1-4-Alkoxycarbonyl-, Aminocarbonyl-, C_1-3-Alkylaminocarbonyl-, Di-(C_1-3-alkyl)-aminocarbonyl-, Di-(C_1-3-alkyl)-amino-, Phenyl-C_1-3-alkylamino- oder N-(C_1-3-Alkyl)-phenyl-C_1-3-alkylaminogruppe substituiert oder
die Methylengruppe in 4-Position einer 6- oder 7-gliedrigen Cycloalkyleniminogruppe durch ein Sauerstoff- oder Schwefelatom, durch eine Sulfinyl-, Sulfonyl-, -NH-, -N(C_1-3-Alkyl)-, -N(Allyl)-, -N(Phenyl)-, -N(Phenyl-C_1-3-alkyl)-, -N(C_1-3-Alkyl-carbonyl)-, -N(C_1-4-Hydroxy-carbonyl)-, -N(C_1-4-Alkoxy-carbonyl)-, -N(Benzoyl)- oder -N(Phenyl-C_1-3-alkyl-carbonyl)-Gruppe ersetzt sein kann,
wobei eine mit einem Imino-Stickstoffatom der Cycloalkyleniminogruppe verknüpfte Methylengruppe durch eine Carbonyl- oder Sulfonylgruppe ersetzt sein kann oder in einer 5- bis 7-gliedrigen monocyclischen oder mit einer Phenylgruppe kondensierten Cycloalkyleniminogruppe beide mit dem Imino-Stickstoffatom verknüpften Methylengruppen jeweils durch eine Carbonylgruppe ersetzt sein können,
bedeutet,
oder R₆ eine Gruppe der Formel -N(R₁₅)-CO-(CH₂)_s-R₁₆ in der
R₁₅ ein Wasserstoffatom, eine Allyl-, C_1-6-Alkyl-, C_3-7-Cycloalkyl- oder Pyridinyl-gruppe,
eine terminal durch eine Phenyl-, Heteroaryl-, Trifluormethyl-, Aminocarbonyl-, C_1-4-Alkylamino-carbonyl-, Di-(C_1-4-alkyl)-amino-carbonyl-, C_1-3-Alkyl-carbonyl-, C_1-3-Alkyl-aminosulfonyl- oder Di-(C_1-3-alkyl)-aminosulfonylgruppe substituierte C_1-3-Alkylgruppe oder
eine terminal durch eine Hydroxy-, C_1-3-Alkoxy-, Amino-, C_1-3-Alkylamino-, Allylamino-, Di-(C_1-3-alkyl)-amino-, C_1-3-Alkyl-sulfonylamino- oder N-(C_1-3-Alkyl)-C_1-3-alkyl-sulfonylaminogruppe substituierte C_2-3-Alkylgruppe und
s eine der Zahlen 0, 1, 2 oder 3 darstellen und
R₁₆ die Bedeutungen der vorstehend erwähnten Gruppe R₇ annimmt oder
eine Carboxygruppe bedeutet oder,
sofern s eine der Zahlen 1, 2 oder 3 darstellt, auch ein Wasserstoffatom bedeutet,
eine Gruppe der Formel -N(R₁₇)-SO₂-R₁₈, in der
R₁₇ ein Wasserstoffatom,
eine Allyl-, C_1-4-Alkyl- oder Cyanomethylgruppe oder
eine terminal durch eine Cyano-, Amino-, C_1-3-Alkylamino-, Di-(C_1-3-alkyl)amino-, Trifluormethyl-carbonyl-amino- oder N-(C_1-3-Alkyl)-trifluormethylcarbonyl-aminogruppe substituierte C_2-4-Alkylgruppe und
R₁₈ eine C_1-4-Alkyl-, Phenyl- oder Pyridylgruppe bedeuten,
eine durch eine Di-(C_1-3-alkyl)-amino-C_1-3-alkyl-carbonyl- oder Di-(C_1-3-alkyl)-amino-C_1-3-alkyl-sulfonylgruppe und eine Di-(C_1-3-alkyl)-aminocarbonyl-C_1-3-alkylgruppe substituierte Aminogruppe,
oder eine Gruppe der Formel -A-(CH₂)_t-R₁₉, in der
A ein Sauerstoff oder Schwefelatom oder eine Sulfinyl- oder Sulfonylgruppe,
R₁₉ ein Wasserstoffatom, eine Hydroxy-, C_1-3-Alkoxy-, Aryl-, Heteroaryl-, Amino-, C_1-4-Alkylamino- oder Di-(C_1-3-alkyl)-aminogruppe
oder eine 4- bis 7-gliedrige Cycloalkyleniminogruppe,
wobei die Methylengruppe in Position 3 einer 5-gliedrigen Cycloalkyleniminogruppe durch eine Hydroxy-, Hydroxy-C_1-3-alkyl-, C_1-3-Alkoxy-C_1-3-alkylgruppe substituiert sein kann,
jeweils die Methylengruppe in Position 3 oder 4 einer 6- oder 7-gliedrigen Cycloalkyleniminogruppe durch eine Hydroxy-, Hydroxy-C_1-3-alkyl-, C_1-3-Alkoxy-, C_1-3-Alkoxy-C_1-3-alkyl-, Carboxy-, C_1-4-Alkoxycarbonyl-, Aminocarbonyl-, C_1-3-Alkylaminocarbonyl- oder Di-(C_1-3-alkyl)-aminocarbonylgruppe substituiert oder
durch ein Sauerstoff- oder Schwefelatom, durch eine Sulfinyl-, Sulfonyl-, -NH- oder -N(C_1-3-Alkyl-)- Gruppe ersetzt sein kann, und
t eine der Zahlen 2 oder 3 oder,
sofern R₁₉ ein Wasserstoffatom, eine Aryl- oder Heteroarylgruppe darstellt, auch die Zahl 1 oder,
sofern A eine Sulfonylgruppe darstellt, auch die Zahl 0 bedeuten,
oder eine Gruppe der Formel -SO₂-N(R₂₀)-(CH₂)_u-R₂₁, in der
R₂₀ ein Wasserstoffatom, eine Allyl- oder C_1-3-Alkylgruppe,
R₂₁ ein Wasserstoffatom, eine Hydroxy-, C_1-3-Alkoxy-, Amino-, C_1-3-Alkylamino- oder eine Di-(C_1-3-alkyl)-aminogruppe und
u eine der Zahlen 2, 3 oder 4 oder,
sofern R₂₁ ein Wasserstoffatom ist, auch die Zahl 1 bedeuten,
wobei alle in den unter R₆ genannten Resten enthaltenen einfach gebundenen oder ankondensierten Phenylgruppen durch Fluor-, Chlor-, Brom- oder Iodatome, durch C_1-5-Alkyl-, Trifluormethyl-, Hydroxy-, C_1-3-Alkoxy-, Carboxy-, C_1-3-Alkoxy-carbonyl-, Aminocarbonyl-, C_1-4-Alkylamino-carbonyl-, Di-(C_1-4-alkyl)-amino-carbonyl-, Aminosulfonyl-, C_1-3-Alkyl-aminosuifonyl-, Di-(C_1-3-alkyl)-aminosulfonyl-, C_1-3-Alkyl-sulfonylamino-, Nitro- oder Cyanogruppen mono- oder disubstituiert sein können, wobei die Substituenten gleich oder verschieden sein können, oder zwei benachbarte Wasserstoffatome der Phenylgruppen durch eine Methylendioxygruppe ersetzt sein können,
oder R₄ eine Gruppe der Formel

in der
R₂₂ eine C_1-3-Alkylgruppe,
R₂₃ ein Wasserstoffatom,
eine Allylgruppe,
eine gegebenenfalls durch eine Cyano-, Carboxy-, Phenyl- oder Pyridylgruppe substituierte C_1-4-Alkylgruppe oder
eine terminal durch eine Hydroxy- oder C_1-3-Alkoxygruppe substituierte C_2-4-Alkylgruppe und
R₂₄ ein Wasserstoffatom,
eine C_1-3-Alkylgruppe,
eine terminal durch eine Hydroxy-, C_1-3-Alkoxy-, C_1-3-Alkylamino- oder Di-(C_1-3-alkyl)-aminogruppe substituierte C_2-3-Alkylgruppe,
oder eine 3-7-gliedrige Cycloalkylgruppe,
wobei eine Methylengruppe durch ein Sauerstoffataom oder durch eine -NH- oder -N(C_1-3-Alkyl)- Gruppe ersetzt sein kann und unabhängig davon eine Methylengruppe durch eine Carbonylgruppe ersetzt sein kann, bedeuten
oder R₂₃ und R₂₄ zusammen mit dem Stickstoffatom, mit dem sie verknüpft sind, bilden
eine 2,5-Dihydro-pyrrol-1-yl-gruppe oder
eine 5- bis 7-gliedrige Cycloalkyleniminogruppe,
wobei die Methylengruppe in Position 4 einer 6- oder 7-gliedrigen Cycloalkyleniminogruppe durch eine Amino-, C_1-3-Alkylamino- oder Di-(C_1-3-alkyl)-aminogruppe substituiert oder durch ein Sauerstoffatom, ein Schwefelatom, eine Sulfinyl- oder Sulfonylgruppe oder eine -NH- oder -N(C_1-3-Alkyl)-Gruppe ersetzt sein kann
und wobei ein oder zwei Wasserstoffatome in der 5- bis 7-gliedrigen Cycloalkyleniminogruppe durch eine C_1-3-Alkylgruppe ersetzt sein können,
und
R₅ ein Wasserstoffatom oder eine C_1-3-Alkylgruppe,
wobei unter dem Ausdruck eine Arylgruppe eine gegebenenfalls durch ein Fluor-, Chlor-, Brom- oder Iodatom, durch eine Cyano-, Trifluormethyl-, Nitro-, Carboxy-, Aminocarbonyl-, C_1-3-Alkyl- oder C_1-3-Alkoxygruppe mono- oder disubstituierte Phenyl- oder Naphthylgruppe und
unter dem Ausdruck eine Heteroarylgruppe, soweit nicht anders angegeben, eine im Kohlenstoffgerüst gegebenenfalls durch eine oder zwei C_1-3-Alkylgruppen substituierte monocyclische 5- oder 6-gliedrige Heteroarylgruppe, wobei
die 6-gliedrige Heteroarylgruppe ein, zwei oder drei Stickstoffatome und
die 5-gliedrige Heteroarylgruppe eine gegebenenfalls durch eine C_1-3-Alkyl- oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe, ein Sauerstoff oder Schwefelatom oder
eine gegebenenfalls durch eine C_1-3-Alkyl- oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe oder ein Sauerstoff oder Schwefelatom und zusätzlich ein Stickstoffatom oder
eine gegebenenfalls durch eine C_1-3-Alkyl- oder Phenyl-C_1-3-alkylgruppe substituierte Iminogruppe und zwei Stickstoffatome enthält,
und außerdem an die vorstehend erwähnten monocyclischen heterocyclischen Gruppen über zwei benachbarte Kohlenstoffatome ein Phenylring ankondensiert sein kann, das Wasserstoffatom einer oder zweier Methingruppen durch eine C_1-3-Alkyl-, Amino-, C_1-3-Alkyl-amino- oder Di-(C_1-3-alkyl)-aminogruppe ersetzt sein kann und die Bindung über ein Stickstoffatom oder über ein Kohlenstoffatom des heterocyclischen Teils oder eines ankondensierten Phenylrings erfolgt,
zu verstehen ist,
die Wasserstoffatome in den vorstehend genannten Alkyl- und Alkoxygruppen oder in den in vorstehend definierten Gruppen der Formel I enthaltenen Alkylteilen teilweise oder ganz durch Fluoratome ersetzt sein können,
die in den vorstehend definierten Gruppen vorhandenen gesättigten Alkyl- und Alkoxyteile, die mehr als zwei Kohlenstoffatome enthalten, auch deren verzweigte Isomere, wie beispielsweise die Isopropyl-, tert.Butyl-, Isobutylgruppe, einschließen, sofern nichts anderes erwähnt wurde, und
wobei zusätzlich das Wasserstoffatom einer vorhandenen Carboxygruppe oder ein an ein Stickstoffatom gebundenes Wasserstoffatom, beispielsweise einer Amino-, Alkylamino- oder Iminogruppe oder eines gesättigten N-Heterocyclus wie der Piperidinylgruppe, jeweils durch einen in-vivo abspaltbaren Rest ersetzt sein kann.In the above general formula I mean
X is an oxygen or sulfur atom,
R _{1 is} a hydrogen atom or a prodrug residue such as a C _1-4 alkoxycarbonyl or C _2-4 alkanoyl group,
R _{2 is} a hydrogen, fluorine, chlorine or bromine atom,
a cyano or nitro group,
a carboxy group, a linear or branched C _1-6 alkoxy-carbonyl group, a C _3-6 cycloalkoxy-carbonyl or an aryloxycarbonyl group,
an allyloxycarbonyl group optionally substituted by one or two methyl groups,
a linear or branched C _1-4 alkoxy-carbonyl group which is terminated in the alkyl part by a phenyl, heteroaryl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino-carbonyl or di (C _1-3 alkyl) aminocarbonyl group is substituted,
a linear or branched C _2-6 alkoxy carbonyl group which is terminated in the alkyl part by a chlorine atom or a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _{1- 3} -alkyl) -amino group is substituted, or
an aminocarbonyl, C _1-4 alkyl aminocarbonyl or a di (C _1-4 alkyl) aminocarbonyl group, where the alkyl groups, if they have more than one carbon atom, are terminated by a hydroxy, C _1-3 Alkoxy or di- (C _1-3 alkyl) amino group can be substituted,
R _{3 is} a five- or six-membered heteroaryl group, where
the 6-membered heteroaryl group has one, two or three nitrogen atoms and
the 5-membered heteroaryl group is an imino group optionally substituted by a C _1-3 alkyl, carboxyC _1-3 alkyl or phenylC _1-3 alkyl group, an oxygen or sulfur atom or
an imino group optionally substituted by a C _1-3 alkyl, carboxyC _1-3 alkyl or phenylC _1-3 alkyl group or an oxygen or sulfur atom and additionally a nitrogen atom or
contains an imino group optionally substituted by a C _1-3 alkyl or phenyl C _1-3 alkyl group, an oxygen atom or a sulfur atom and two nitrogen atoms,
and furthermore, a phenyl ring may be fused to the monocyclic heterocyclic groups mentioned above via two adjacent carbon atoms, the hydrogen atom of a methine group by a C _1-3 alkyl, carboxyC _1-3 alkyl, amino, C _1-3 Alkylamino, di (C _1-3 alkyl) amino, phenylC _1-3 alkylamino or di (phenylC _1-3 alkyl) amino group can be replaced and the bond takes place via a carbon atom of the heterocyclic part,
a 5- to 6-membered cyclic oxime ether which is linked to the methylidene group via the carbon atom adjacent to the nitrogen atom,
or a bicyclic group consisting of
a phenyl ring linked to the methylidene group, and
one -O-CH ₂ -O-, -O-CF ₂ -O-, -O-CH ₂ -CH ₂ -O-, -O-CH = CH-O-, -S-CH = N-, - NH-CH = N-, -N = C (C _1-3 alkyl) -NH-, -N = C (carboxy-C _1-3 alkyl) -NH-, -N (C _1-3 alkyl ) -CH = N-, -N (carboxy-C _1-3 alkyl) -CH = N-, -N (C _1-3 alkyl) -C (C _1-3 - alkyl) = N-, - N = CH-CH = N-, -N = CH-N = CH-, -N = CH-N = C (C _1-3 alkyl) -, -N = CH-N = C (carboxy-C _{1 -3-} alkyl) -, -N = CH-CH = CH-, -N = CH-CH = C (C _1-3 alkyl) -, -N = CH-CH = C (carboxy-C _1-3 -alkyl) -, -N = N-NH-, -N = NN (C _1-3 alkyl) -, -N = NN (carboxy-C _1-3 alkyl) -, -CH = CH-NH- , -CH = CH-N (C _1-3 alkyl) -, -CH = CH-N (carboxy-C _1-3 alkyl) -, -N = CH-C (O) -N (C _{1- 3} - alkyl) -, -O-CH ₂ C (O) -N (C _1-3 alkyl) -, -CH = NN = CH-, -OC (O) -CHN ₂ (C _1-3 alkyl) ) -, -O-CH ₂ C (O) -NH-, -O-CH ₂ CH ₂ N (C _1-3 alkyl) -, -OC (O) -N (C _1-3 alkyl) - , -OC (O) -NH-, -CO-NH-CO- or -CO-N (C _1-3 -alkyl) -CO-bridge, each of which is linked to two adjacent carbon atoms of the phenyl ring,
R _{4 is} a C _3-7 cycloalkyl group,
where the methylene group in position 4 of a 6- or 7-membered cycloalkyl group is substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or by an -NH- or -N ( C _1-3 alkyl) group can be replaced,
or a phenyl group substituted by the group R ₆ in the 3- or 4-position, which is additionally substituted by fluorine, chlorine, bromine or iodine atoms, by C _1-5 -alkyl, trifluoromethyl, hydroxy, C _1-3 -Alkoxy-, carboxy-, C _1-3 -alkoxycarbonyl-, amino-, acetylamino-, C _1-3 -alkyl-sulfonylamino-, aminocarbonyl-, C _1-3 -alkyl-aminocarbonyl-, di- (C _{1- 3} -alkyl) -aminocarbonyl-, aminosulfonyl-, C _1-3 -alkyl-aminosulfonyl-, di- (C _1-3 -alkyl) -aminosulfonyl-, nitro or cyano groups can be mono- or disubstituted, the substituents being the same or can be different and where
R _{6 is} a hydrogen, fluorine, chlorine, bromine or iodine atom,
a cyano, nitro, amino, C _1-5 alkyl, C _3-7 cycloalkyl, trifluoromethyl, phenyl or heteroaryl group,
a tetrazolyl group optionally substituted by a C _1-3 alkyl group,
a 2-pyrrolidon-1-yl group, in which the methylene group adjacent to the carbonyl group can be replaced by an oxygen atom or an -NH or -N (C _1-3 -alkyl) group,
the group of the formula

in which the hydrogen atoms bonded to a nitrogen atom can each be replaced independently of one another by a C _1-3 alkyl group,
a group of the formula - (CH ₂ ) _n -CO-R ₈ in the
R _{8 is} a hydroxy or C _1-4 alkoxy group,
a 5- to 7-membered cycloalkyleneimino group,
where the methylene group in position 3 or 4 of a 5-, 6- or 7-membered cycloalkyleneimino group can be substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group
or the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group by an oxygen atom, a sulfur atom, a sulfinyl or sulfonyl group, an -NH-, -N (allyl) - or -N (C _1-3 -alkyl) - Group can be replaced
and in the said cyclic groups one or two hydrogen atoms can be replaced by a C _1-3 alkyl group,
a 2,5-dihydropyrrol-1-yl group or
a C _3-7 cycloalkyl group,
wherein the methylene group in position 3 or 4 of the 5-, 6- or 7-membered cycloalkyl part is substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or
the methylene group in position 4 of the 6- or 7-membered cycloalkyl part can be replaced by a -NH-, -N (allyl) - or -N (C _1-3 -alkyl) group,
and n is one of the numbers 0, 1 or 2,
a group of the formula - (CH ₂ ) _o -CO-NR ₉ R ₁₀ , in the
R _{9 is} a hydrogen atom,
an allyl group,
a C _1-4 alkyl group optionally substituted by a cyano, carboxy, phenyl or pyridyl group or
a C _2-4 alkyl group which is terminally substituted by a hydroxy or C _1-3 alkoxy group,
R _{10 is} a hydrogen atom,
a C _1-3 alkyl group,
a terminally substituted by a hydroxy, C _1-3 alkoxy, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or C _2-3 alkyl group
a 3- to 7-membered cycloalkyl group,
in which a methylene group can be replaced by an oxygen atom or an -NH- or -N (C _1-3 -alkyl) group and independently of this a methylene group can be replaced by a carbonyl group,
and o is one of the numbers 0, 1 or 2,
a C _1-3 alkyl group substituted by the group R ₇ , where
R _{7 is} a C _3-7 cycloalkyl group,
wherein one of the methylene groups is substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or
the methylene group in position 3 or 4 of a 5-, 6- or 7-membered cycloalkyl group can be replaced by an -NH-, -N (allyl) - or -N (C _1-3 -alkyl) group or
in a 5- to 7-membered cycloalkyl group a - (CH ₂ ) ₂ group can be replaced by a -CO-NH group, a - (CH ₂ ) ₃ group by a -NH-CO-NH- or - CO-NH-CO group can be replaced or a - (CH ₂ ) ₄ group can be replaced by a -NH-CO-NH-CO group, where in each case a hydrogen atom bonded to a nitrogen atom is replaced by a C _1-3 Alkyl group can be replaced
an aryl or heteroaryl group,
a triazolyl group,
a hydroxy or C _1-3 alkoxy group, an amino, C _1-7 alkylamino, di (C _1-7 alkyl) amino, N- (C _1-7 alkyl) allylamino , Phenylamino, N-phenyl-C _1-3 alkylamino, phenyl-C _1-3 alkylamino, N- (C _1-3 alkyl) phenyl-C _1-3 alkylamino or di - (phenyl-C _1-3 alkyl) amino group,
an allylamino group in which one or two vinyl hydrogen atoms can each be replaced by a methyl group,
a ω-hydroxy-C _2-3 -alkyl-amino-, N- (C _1-3 -alkyl) -ω-hydroxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _{2- 3} -alkyl) -amino-, ω- (C _1-3 -alkoxy) -C _2-3 -alkyl-amino-N- (C _1-3 -alkyl) - [ω- (C _1-3 -alkoxy) -C _2-3 alkyl) amino, di- [ω- (C _1-3 alkoxy) -C _2-3 alkyl] amino or N- (dioxolan-2-yl) -C _{1- 3} alkyl amino group,
a C _1-3 -alkylcarbonylamino-C _2-3 -alkylamino- or C _1-3 -alkylcarbonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
a pyridylamino group,
a C _1-3 -alkylsulfonylamino-, N- (C _1-3 -alkyl) -C _1-3 -alkylsulfonylamino-, C _1-3 -alkylsulfonylamino-C _2-3 -alkyl-amino- or C _1-3 - Alkylsulfonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
a hydroxycarbonyl-C _1-3 -alkylamino- or N- (C _1-3 -alkyl) -hydroxycarbonyl-C _1-3 -alkyl-amino group,
a guanidino group in which one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group,
a 2-pyrrolidon-1-yl group in which the methylene group adjacent to the carbonyl group can be replaced by an oxygen atom or by an -NH or -N (C _1-3 -alkyl) group,
a group of the formula -N (R ₁₁ ) -CO- (CH ₂ ) _p -R ₁₂ , in the
R _{11 is} a hydrogen atom or an allyl, C _1-3 alkyl, C _1-3 alkyl amino C _2-3 alkyl or di (C _1-3 alkyl) amino C _{2- 3} -alkyl group,
p is one of the numbers 0, 1, 2 or 3 and
R _{12 is} an amino, C _1-3 alkylamino, allylamino, di-allylamino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-4 alkyl) ) phenylamino, benzylamino, N- (C _1-4 alkyl) benzylamino, C _1-4 alkoxy or 2,5-dihydropyrrol-1-yl group or
a 4- to 7-membered cycloalkyleneimino group,
where the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group is represented by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl) -, -N (allyl) -, -N (phenyl) -, -N (C _1-3 alkylcarbonyl) - or -N (benzoyl) group can be replaced,
or, if n represents one of the numbers 1, 2 or 3, also denote a hydrogen atom,
a group of the formula -N (R ₁₃ ) - (CH ₂ ) _q - (CO) _r -R ₁₄ in the
R _{13 is} a hydrogen atom or a C _1-3 alkyl, allyl, C _1-3 alkyl carbonyl, arylcarbonyl, pyridylcarbonyl, phenyl C _1-3 alkyl carbonyl, C _1-3 - Alkylsulfonyl, arylsulfonyl or phenylC _1-3 alkylsulfonyl group,
q one of the numbers 1, 2, 3 or 4,
r the number 1 or, if q is one of the numbers 2, 3 or 4, also the number 0 and
R _{14 is} hydroxy, amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino , N- (C _1-4 alkyl) benzylamino, C _1-4 alkoxy or C _1-3 alkoxy-C _1-3 alkoxy group,
a di- (C _1-4 -alkyl) -amino-C _1-3 -alkylamino group which is optionally substituted in the 1-position by a C _1-3 alkyl group or
a 4- to 7-membered cycloalkyleneimino group,
wherein the cycloalkylene part can be condensed with a phenyl ring or
each the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl) -, -N (phenyl) - , -N (C _1-3 alkylcarbonyl) - or -N (benzoyl) group may be replaced,
a C _4-7 cycloalkylamino, C _4-7 cycloalkyl-C _1-3 alkylamino or C _4-7 cycloalkenylamino group in which position 1 of the ring is not involved in the double bond and wherein the groups mentioned above can each additionally be substituted on the amine nitrogen atom by a C _{5 -7} cycloalkyl, C _{2 -4} alkenyl or C _1-4 alkyl group,
a 2,5-dihydro-pyrrol-1-yl group or
a 4- to 7-membered cycloalkyleneimino group in which the cycloalkylene part with a phenyl group or with one optionally through a fluorine, chlorine, bromine or iodine atom, through a nitro, C _1-3 alkyl, C _1-3 Alkoxy or amino group substituted oxazolo, imidazolo, thiazolo, pyridino, pyrazino or pyrimidino group can be condensed or / and
one or two hydrogen atoms each through a C _1-3 alkyl, C _3-7 cycloalkyl, hydroxy, C _1-3 alkoxy, hydroxy C _1-3 alkyl, C _1-3 alkoxy -C _1-3 alkyl or phenyl group can be replaced or / and
the methylene group in position 3 of a 5-membered cycloalkyleneimino group can be substituted by a hydroxy, hydroxyC _1-3 alkyl, C _1-3 alkoxy or C _1-3 alkoxyC _1-3 alkyl group,
each the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group by a hydroxy, hydroxyC _1-3 alkyl, C _1-3 alkoxy, C _1-3 alkoxyC _1-3 -alkyl-, carboxy-, C _1-4 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocarbonyl-, di- (C _1-3 -alkyl) -aminocarbonyl-, di- (C _1-3 -alkyl) -amino-, phenyl-C _1-3 -alkylamino- or N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino group substituted or
the methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group through an oxygen or sulfur atom, through a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl) -, -N (allyl) -, -N (phenyl) -, -N (phenyl-C _1-3 -alkyl) -, -N (C _1-3 -alkyl-carbonyl) -, -N (C _1-4 -hydroxy-carbonyl) - , -N (C _1-4 -alkoxy-carbonyl) -, -N (benzoyl) - or -N (phenyl-C _1-3 -alkyl-carbonyl) group can be replaced,
wherein a methylene group linked to an imino nitrogen atom of the cycloalkyleneimino group can be replaced by a carbonyl or sulfonyl group or in a 5- to 7-membered monocyclic or fused to a phenyl group cycloalkyleneimino group, both methylene groups linked to the imino nitrogen atom can each be replaced by a carbonyl group can,
means
or R _{6 is} a group of the formula -N (R ₁₅ ) -CO- (CH ₂ ) _s -R ₁₆ in the
R _{15 represents} a hydrogen atom, an allyl, C _1-6 alkyl, C _3-7 cycloalkyl or pyridinyl group,
a terminal by a phenyl, heteroaryl, trifluoromethyl, aminocarbonyl, C _1-4 alkylamino carbonyl, di (C _1-4 alkyl) amino carbonyl, C _1-3 alkyl carbonyl -, C _1-3 alkylaminosulfonyl or di (C _1-3 alkyl) aminosulfonyl group substituted C _1-3 alkyl group or
one terminal by a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, allylamino, di (C _1-3 alkyl) amino, C _1-3 alkyl sulfonylamino or N- (C _1-3 alkyl) -C _1-3 alkyl sulfonylamino group substituted C _2-3 alkyl group and
s represent one of the numbers 0, 1, 2 or 3 and
R _{16 takes} the meanings of the aforementioned group R ₇ or
represents a carboxy group or,
if s represents one of the numbers 1, 2 or 3, also denotes a hydrogen atom,
a group of the formula -N (R ₁₇ ) -SO ₂ -R ₁₈ , in the
R _{17 is} a hydrogen atom,
an allyl, C _1-4 alkyl or cyanomethyl group or
a terminal by a cyano, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, trifluoromethylcarbonylamino or N- (C _1-3 alkyl) trifluoromethylcarbonyl -amino group substituted C _2-4 alkyl group and
R _{18 represents} a C _1-4 alkyl, phenyl or pyridyl group,
one by a di (C _1-3 alkyl) amino C _1-3 alkyl carbonyl or di (C _1-3 alkyl) amino C _1-3 alkyl sulfonyl group and a di - (C _1-3 -alkyl) -aminocarbonyl-C _1-3 -alkyl group substituted amino group,
or a group of the formula -A- (CH ₂ ) _t -R ₁₉ , in the
A is an oxygen or sulfur atom or a sulfinyl or sulfonyl group,
R _{19 is} a hydrogen atom, a hydroxy, C _1-3 alkoxy, aryl, heteroaryl, amino, C _1-4 alkylamino or di (C _1-3 alkyl) amino group
or a 4- to 7-membered cycloalkyleneimino group,
where the methylene group in position 3 of a 5-membered cycloalkyleneimino group can be substituted by a hydroxy, hydroxyC _1-3 alkyl, C _1-3 alkoxyC _1-3 alkyl group,
each the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group by a hydroxy, hydroxyC _1-3 alkyl, C _1-3 alkoxy, C _1-3 alkoxyC _1-3 alkyl, carboxy, C _1-4 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 alkyl) aminocarbonyl group or substituted
can be replaced by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH or -N (C _1-3 alkyl) group, and
t one of the numbers 2 or 3 or,
if R _{19 represents} a hydrogen atom, an aryl or heteroaryl group, also the number 1 or,
if A represents a sulfonyl group, also denote the number 0,
or a group of the formula -SO ₂ -N (R ₂₀ ) - (CH ₂ ) _u -R ₂₁ , in the
R _{20 represents} a hydrogen atom, an allyl or C _1-3 alkyl group,
R _{21 represents} a hydrogen atom, a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or a di (C _1-3 alkyl) amino group and
u one of the numbers 2, 3 or 4 or,
if R _{21 is} a hydrogen atom, also denote the number 1,
where all the single-bonded or fused-on phenyl groups contained in the radicals mentioned under R _{6 are represented} by fluorine, chlorine, bromine or iodine atoms, by C _1-5 -alkyl, trifluoromethyl, hydroxy, C _1-3 -alkoxy-, Carboxy-, C _1-3 -alkoxy-carbonyl-, aminocarbonyl-, C _1-4 -alkylamino-carbonyl-, di- (C _1-4 -alkyl) -amino-carbonyl-, aminosulfonyl-, C _1-3 - Alkyl aminosuifonyl, di (C _1-3 alkyl) aminosulfonyl, C _1-3 alkyl sulfonylamino, nitro or cyano groups can be mono- or disubstituted, where the substituents can be the same or different, or two adjacent hydrogen atoms of the phenyl groups can be replaced by a methylenedioxy group,
or R _{4 is} a group of the formula

in the
R _{22 is} a C _1-3 alkyl group,
R _{23 is} a hydrogen atom,
an allyl group,
a C _1-4 alkyl group optionally substituted by a cyano, carboxy, phenyl or pyridyl group or
a terminally substituted by a hydroxy or C _1-3 alkoxy group, C _2-4 alkyl group and
R _{24 is} a hydrogen atom,
a C _1-3 alkyl group,
a C _2-3 alkyl group which is terminally substituted by a hydroxy, C _1-3 alkoxy, C _1-3 alkylamino or di (C _1-3 alkyl) amino group,
or a 3-7-membered cycloalkyl group,
where a methylene group can be replaced by an oxygen atom or by an -NH- or -N (C _1-3 alkyl) group and independently of this a methylene group can be replaced by a carbonyl group
or R ₂₃ and R ₂₄ together with the nitrogen atom to which they are linked form
a 2,5-dihydro-pyrrol-1-yl group or
a 5- to 7-membered cycloalkyleneimino group,
wherein the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group is substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or by an oxygen atom, a sulfur atom, a sulfinyl - Or sulfonyl group or an -NH or -N (C _1-3 alkyl) group can be replaced
and one or two hydrogen atoms in the 5- to 7-membered cycloalkyleneimino group can be replaced by a C _1-3 alkyl group,
and
R _{5 represents} a hydrogen atom or a C _1-3 alkyl group,
where under the expression an aryl group, optionally by a fluorine, chlorine, bromine or iodine atom, by a cyano, trifluoromethyl, nitro, carboxy, aminocarbonyl, C _1-3 alkyl or C _1-3 -Alkoxy group mono- or disubstituted phenyl or naphthyl group and
under the expression a heteroaryl group, unless otherwise stated, a monocyclic 5- or 6-membered heteroaryl group optionally substituted in the carbon skeleton by one or two C _1-3 alkyl groups, where
the 6-membered heteroaryl group has one, two or three nitrogen atoms and
the 5-membered heteroaryl group is an imino group optionally substituted by a C _1-3 alkyl or phenylC _1-3 alkyl group, an oxygen or sulfur atom or
an imino group optionally substituted by a C _1-3 alkyl or phenyl C _1-3 alkyl group or an oxygen or sulfur atom and additionally a nitrogen atom or
contains an imino group optionally substituted by a C _1-3 alkyl or phenyl C _1-3 alkyl group and two nitrogen atoms,
and also a phenyl ring may be fused to the above-mentioned monocyclic heterocyclic groups via two adjacent carbon atoms, the hydrogen atom of one or two methine groups by a C _1-3 alkyl, amino, C _1-3 alkyl amino or di (C _1-3 alkyl) amino group can be replaced and the bond takes place via a nitrogen atom or via a carbon atom of the heterocyclic part or a fused-on phenyl ring,
to understand
the hydrogen atoms in the alkyl and alkoxy groups mentioned above or in the alkyl parts contained in the groups of formula I defined above can be partially or completely replaced by fluorine atoms,
the saturated alkyl and alkoxy parts present in the groups defined above, which contain more than two carbon atoms, including their branched isomers, such as, for example, the isopropyl, tert-butyl, isobutyl group, unless stated otherwise, and
where in addition the hydrogen atom of an existing carboxy group or a hydrogen atom bonded to a nitrogen atom, for example an amino, alkylamino or imino group or a saturated N-heterocycle such as the piperidinyl group, can each be replaced by a residue which can be split off in vivo.

Among a residue which can be split off from an imino or amino group in vivo is, for example, a hydroxyl group, an acyl group such as the benzoyl or pyridinoyl group or a C _1-16 alkanoyl group such as the formyl, acetyl, propionyl, butanoyl, pentanoyl or hexanoyl group, an allyloxycarbonyl group, a C _1-16 alkoxycarbonyl group such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert.butoxycarbonyl, pentoxycarbonyl, hexyloxycarbonyl, octyloxycarbonyl, nonyloxycarbonyl, decyloxycarbonyl, Undecyloxycarbonyl, dodecyloxycarbonyl or hexadecyloxycarbonyl group, a phenyl C _1-6 alkoxycarbonyl group such as the benzyloxycarbonyl, phenylethoxycarbonyl or phenylpropoxycarbonyl group, a C _1-3 alkylsulfonyl C _2-4 alkoxycarbonyl, C _1-3 alkoxy- C _2-4 -acoxy-C _2-4 -alkoxycarbonyl or R _e CO-O- (R _f CR _g ) -O-CO group, in which
R _{e is} a C _1-8 alkyl, C _{5 -7} cycloalkyl, phenyl or phenyl C _1-3 alkyl group,
R _{f is} a hydrogen atom, a C _1-3 alkyl, C _5-7 cycloalkyl or phenyl group and
R _{g is} a hydrogen atom, a C _1-3 alkyl or R _e CO-O- (R _f CR _g ) -O group, in which R _e to R _g as above are defined, represent,
where additionally the phthalimido group is to be considered for an amino group, the above-mentioned ester radicals also being able to be used as a group which can be converted into a carboxy group in vivo.

in der
R₂₂ eine Methylgruppe,
R₂₃ ein Wasserstoffatom oder eine Allyl- oder C_1-3-Alkylgruppe und
R₂₄ ein Wasserstoffatom, eine C_1-3-Alkylgruppe oder
eine terminal durch eine Hydroxy-, C_1-3-Alkoxy-, C_1-3-Alkylaminogruppe oder durch eine Di-(C_1-3-alkyl)-aminogruppe substituierte C_2-3-Alkylgruppe bedeuten,
oder R₂₃ und R₂₄ zusammen mit dem Stickstoffatom, mit dem sie verknüpft sind, bilden
eine 2,5-Dihydro-pyrrol-1-yl-gruppe oder
eine 5- bis 7-gliedrige Cycloalkyleniminogruppe,
wobei die Methylengruppe in Position 4 einer 6- oder 7-gliedrigen Cycloalkyleniminogruppe durch eine Amino-, C_1-3-Alkylamino- oder Di-(C_1-3-alkyl)-aminogruppe substituiert oder durch ein Sauerstoffatom, eine -NH- oder -N(C_1-3-Alkyl)-Gruppe ersetzt sein kann,
und
R₅ ein Wasserstoffatom bedeuten,
wobei die Wasserstoffatome in den vorstehend genannten Alkyl- und Alkoxygruppen oder in den in vorstehend definierten Gruppen der Formel I enthaltenen Alkylteilen teilweise oder ganz durch Fluoratome ersetzt sein können,
die in den vorstehend definierten Gruppen vorhandenen gesättigten Alkyl- und Alkoxyteile, die mehr als 2 Kohlenstoffatome enthalten, auch deren verzweigte Isomere, wie beispielsweise die Isopropyl-, tert.Butyl-, Isobutylgruppe, einschließen, sofern nichts anderes erwähnt wurde.Preferred compounds of general formula I are those in which
X is an oxygen atom,
R _{1 is} a hydrogen atom or a prodrug residue such as a C _1-4 alkoxycarbonyl or C _2-4 alkanoyl group,
R _{2 is} a hydrogen, fluorine, chlorine or bromine atom,
a cyano or nitro group,
a carboxy group, a linear or branched C _1-4 alkoxy-carbonyl group or a C _3-4 -cycloalkoxy-carbonyl group,
an allyloxycarbonyl group optionally substituted by one or two methyl groups,
a linear or branched C _2-3 alkoxy-carbonyl group which is terminally substituted in the alkyl part by a hydroxy or C _1-3 alkoxy group, or
an aminocarbonyl, C _1-4 alkyl aminocarbonyl or a di (C _1-3 alkyl) aminocarbonyl group, the alkyl groups, if they have more than one carbon atom, terminally substituted by a C _1-3 alkoxy group could be,
R _{3 is} 2-pyrrolyl, 3-pyrrolyl, 1- (C _1-3 alkyl) -3-pyrrolyl, 1- (carboxy-C _1-3 alkyl) -3-pyrrolyl, 2-furyl -, 3-furyl-, 2-thienyl-, 3-thienyl-, 2- (carboxy-C _1-3 -alkyl) -thien-5-yl-, 2- (carboxy-C _1-3 -alkyl) - thien-4-yl-, 4-imidazolyl-, 1- (C _1-3 alkyl) -5-imidazolyl-, 1- (C _1-3 alkyl) -4-imidazolyl-, 1-benzyl-5- imidazolyl, 5- (C _1-3 alkyl) isoxazol-3-yl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 4-pyridazinyl group or
a pyrazol-3-yl group,
in which, independently of one another, the 1- and / or 5-position can each be substituted by a C _1-3 -alkyl or carboxy-C _1-3 -alkyl group,
a 5- to 6-membered cyclic oxime ether which is linked to the methylidene group via the carbon atom adjacent to the nitrogen atom,
or a bicyclic group consisting of
a phenyl ring linked to the methylidene group, and
one -O-CH ₂ -O-, -O-CF ₂ -O-, -O-CH ₂ -CH ₂ -O-, -O-CH = CH-O-, -S-CH = N-, - NH-CH = N-, -N = C (C _1-3 alkyl) -NH-, -N = C (carboxy-C _1-3 alkyl) -NH-, -N (C _1-3 alkyl ) -CH = N-, -N (carboxy-C _1-3 alkyl) -CH = N-, -N (C _1-3 alkyl) -C (C _1-3 alkyl) = N-, - N = CH-CH = N-, -N = CH-N = CH-, -N = CH-N = C (C _1-3 alkyl) -, -N = CH-CH = CH-, -N = CH-CH = C (C _1-3 alkyl) -, -CH = NN = CH-, -CH = CH-NH-, -CH = CH-N (C _1-3 alkyl) -, -N = N-NH-, -N = NN (C _1-3 alkyl) -, -O-CH ₂ C (O) -N (C _1-3 alkyl) -, -OC (O) -CH ₂ N ( C _1-3 alkyl) -, -OC (O) -N (C _1-3 alkyl) -, -OC (O) -NH-, -O-CH ₂ -CH ₂ N (C _1-3 - Alkyl) -, or -CO-N (C _1-3 -alkyl) -CO bridge, which is in each case linked to two adjacent carbon atoms of the phenyl ring,
R _{4 is} a 1-methyl-piperidin-4-yl group,
or a phenyl group substituted by the group R ₆ in the 3- or 4-position, which additionally has a fluorine, chlorine, bromine or iodine atom or a C _1- in a remaining 3-, 4- or 5-position ₃ -Alkyl-, trifluoromethyl-, hydroxy-, C _1-3 -alkoxy-, amino-, nitro- or cyano group can be substituted, whereby
R _{6 is} a hydrogen, fluorine, chlorine, bromine or iodine atom,
a tetrazolyl group optionally substituted by a C _1-3 alkyl group,
an imidazolyl group substituted on the imino nitrogen and / or on a carbon atom by a C _1-3 alkyl group,
a pyrazolyl group on the imino nitrogen and / or on one or two carbon atoms, each independently substituted by a C _1-3 alkyl group, a 2-pyrrolidon-1-yl group in which the methylene group adjacent to the carbonyl group is replaced by an oxygen atom or an -NH - or -N (C _1-3 alkyl) group can be replaced,
a group of the formula - (CH ₂ ) _n CO-R ₈ , in the
R _{8 is} a hydroxy group,
a 2,5-dihydropyrrol-1-yl group or
a 5- to 7-membered cycloalkyleneimino group,
where the methylene group in position 3 or 4 of a 5-, 6- or 7-membered cycloalkyleneimino group can be substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group
or the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group can be replaced by an oxygen atom, a sulfur atom, a sulfinyl or sulfonyl group, an -NH or -N (C _1-3 -alkyl) group
and in the said cyclic groups one or two hydrogen atoms can be replaced by a C _1-3 alkyl group,
and n is one of the numbers 0 or 1,
a group of the formula - (CH ₂ ) _o -CO-NR ₉ R ₁₀ , in the
R _{9 is} a hydrogen atom,
an allyl group,
a C _1-4 alkyl group optionally substituted by a cyano or carboxy group or
a C _2-4 alkyl group which is terminally substituted by a hydroxy or C _1-3 alkoxy group,
R _{10 is} a hydrogen atom,
a C _1-3 alkyl group,
a terminally substituted by a hydroxy, C _1-3 alkoxy, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or C _2-3 alkyl group
a 3- to 7-membered cycloalkyl group,
in which a methylene group can be replaced by an oxygen atom or an -NH or -N (C _1-3 alkyl) group,
and o is one of the numbers 0 or 1,
a C _1-2 alkyl group substituted by the group R ₇ , where
R _{7 is} a C _3-7 cycloalkyl group,
wherein the methylene group in position 4 of a 6- or 7-membered cycloalkyl group can be replaced by a -NH- or -N (C _1-3 alkyl) group or
a pyridyl or imidazolyl group optionally substituted by a C _1-3 alkyl group,
a triazolyl group,
a hydroxy or C _1-3 alkoxy group,
an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, N- (C _1-3 alkyl) allylamino, phenylC _1-2 alkylamino or N- (C _1-3 alkyl) phenyl-C _1-2 alkylamino group,
an allylamino group in which one or two vinyl hydrogen atoms can each be replaced by a methyl group,
a ω-hydroxy-C _2-3 -alkyl-amino-, N- (C _1-3 -alkyl) -ω-hydroxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _{2- 3} -alkyl) -amino-, ω- (C _1-3 -alkoxy) -C _2-3 -alkyl-amino-N- (C _1-3 -alkyl) - [ω- (C _1-3 -alkoxy) -C _2-3 alkyl] amino or di- [ω- (C _1-3 alkoxy) -C _1-3 alkyl] amino group,
a pyridylamino group,
an N- (C _1-3 alkyl) -C _1-3 alkylsulfonylamino group,
a hydroxycarbonyl-C _1-3 -alkylamino- or N- (C _1-3 -alkyl) -hydroxycarbonyl-C _1-3 -alkyl-amino group,
a 2-pyrrolidon-1-yl group, in which the methylene group adjacent to the carbonyl group can be replaced by an oxygen atom or an -NH or -N (C _1-3 -alkyl) group,
a group of the formula -N (R ₁₁ ) -CO- (CH ₂ ) _p -R ₁₂ , in the
R _{11 represents} a hydrogen atom or an allyl, C _1-3 alkyl group, C _1-3 alkylamino C _{2 -3} alkyl or di (C _1-3 alkyl) amino C _2-3 alkyl group .
p one of the numbers 0, 1 or 2 and
R _{12 is} an amino, C _1-3 alkylamino, allylamino, di (C _1-3 alkyl) amino, C _1-3 alkoxy or 2,5-dihydropyrrol-1-yl group or
a 4- to 7-membered cycloalkyleneimino group,
where in each case the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group can be replaced by an oxygen or sulfur atom, by an -NH-, -N (allyl) - or -N (C _1-3 -alkyl) group,
or, if n represents one of the numbers 1 or 2, also denote a hydrogen atom,
a group of the formula -N (R ₁₃ ) - (CN ₂ ) _q - (CO) _r -R ₁₄ in the
R _{13 represents} a hydrogen atom or a C _1-3 alkyl or pyridylcarbonyl group,
q one of the numbers 1 or 2,
r the number 1 or, if q is the number 2, the number 0 and
R _{14 is} a hydroxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, C _1-3 alkoxy group or
a 4- to 7-membered cycloalkyleneimino group,
where in each case the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group can be replaced by an oxygen or sulfur atom, by an -NH- or -N (C _1-3 -alkyl) group,
a C _{4 -7} cycloalkylamino, C _3-5 cycloalkyl-C _1-2 alkylamino or C _4-7 cycloalkenylamino group in which position 1 of the ring is not involved in the double bond and wherein the groups mentioned above can each additionally be substituted on the amine nitrogen atom by a C _{2 -4} alkenyl or C _1-3 alkyl group,
a 2,5-dihydro-pyrrol-1-yl group or
a 4- to 7-membered cycloalkyleneimino group in which
one or two hydrogen atoms are each replaced by a C _1-3 alkyl, hydroxy, C _1-3 alkoxy, hydroxy C _1-3 alkyl or C _1-3 alkoxy C _1-3 alkyl group can be or / and
each substituted the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group with a carboxy, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 alkyl) aminocarbonyl group or
the methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group through an oxygen or sulfur atom, through a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl -) -, -N (allyl ) - or -N (C _1-3 alkylcarbonyl) group can be replaced,
where a methylene group linked to an imino nitrogen atom of the cycloalkyleneimino group can be replaced by a carbonyl or sulfonyl group,
means
or R _{6 is} a group of the formula -N (R ₁₅ ) -CO- (CH ₂ ) _s -R ₁₆ in the
R _{15 represents} a hydrogen atom, an allyl, C _1-4 alkyl, C _3-5 cycloalkyl or pyridinyl group,
a terminally substituted by a pyridyl, trifluoromethyl or di (C _1-2 alkyl) amino carbonyl group C _1-3 alkyl group or
a terminal by a hydroxy, C _1-3 alkoxy, amino, C _1-3 -alkylamino or di- (C _1-3 alkyl) amino-substituted C _2-3 alkyl group and
s represent one of the numbers 0, 1, 2 or 3 and
R _{16 is} a hydroxy, C _1-3 alkoxy, carboxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, 2,5-dihydropyrrol-1- yl or pyridinyl group or a 5- to 7-membered cycloalkyleneimino group,
where the methylene group in position 3 of a 5-membered cycloalkyleneimino group can be substituted by a hydroxy, hydroxyC _1-3 alkyl or C _1-3 alkoxyC _1-3 alkyl group,
each the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group by a di- (C _1-3 alkyl) amino, hydroxy, hydroxy-C _1-3 alkyl, C _1-3 - Alkoxy or C _1-3 alkoxy-C _1-3 alkyl group substituted or
the methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group can be replaced by an oxygen or sulfur atom, by an -NH or -N (C _1-3 -alkyl-) - group,
or, if s represents one of the numbers 1, 2 or 3, also denotes a hydrogen atom,
a group of the formula -N (R ₁₇ ) -SO ₂ -R ₁₈ , in the
R _{17 is} a hydrogen atom,
a C _1-3 alkyl or cyanomethyl group or
a C _2-3 alkyl group terminally substituted by a cyano, amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group and
R _{18 represents} a C _1-4 alkyl or pyridyl group,
or a group of the formula -A- (CH ₂ ) _t -R ₁₉ in the
A is an oxygen or sulfur atom or a sulfinyl or sulfonyl group,
R _{19 represents} a hydrogen atom or a hydroxy, C _1-3 alkoxy, amino, C _1-4 alkylamino or di (C _1-3 alkyl) amino group
or a 4- to 7-membered cycloalkyleneimino group,
where in each case the methylene group in position 3 or 4 of a 6- or 7-membered group can be replaced by an oxygen or sulfur atom or by an -NH or -N (C _1-3 -alkyl) group,
and t one of the numbers 2 or 3
or, if R _{19 is} a hydrogen atom, also mean the number 1
or a group of the formula -SO ₂ -N (R ₂₀ ) - (CH ₂ ) _u -R ₂₁ , in the
R _{20 represents} a hydrogen atom or an allyl or C _1-3 alkyl group,
R _{21 represents} a hydrogen atom, a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or a di (C _1-3 alkyl) amino group and
u one of the numbers 2, 3 or 4
or, if R _{21 is} a hydrogen atom, also denote the number 1,
or R _{4 is} a group of the formula

in the
R _{22 is} a methyl group,
R _{23 is} a hydrogen atom or an allyl or C _1-3 alkyl group and
R _{24 is} a hydrogen atom, a C _1-3 alkyl group or
a terminally substituted by a hydroxy, C _1-3 alkoxy, C _1-3 alkylamino group or by a di (C _1-3 alkyl) amino group C _2-3 alkyl group,
or R ₂₃ and R ₂₄ together with the nitrogen atom to which they are linked form
a 2,5-dihydro-pyrrol-1-yl group or
a 5- to 7-membered cycloalkyleneimino group,
wherein the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group is substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or by an oxygen atom, an -NH- or -N (C _1-3 alkyl) group can be replaced,
and
R _{5 represents} a hydrogen atom,
where the hydrogen atoms in the alkyl and alkoxy groups mentioned above or in the alkyl parts contained in the groups of formula I defined above can be partially or completely replaced by fluorine atoms,
the saturated alkyl and alkoxy parts present in the groups defined above which contain more than 2 carbon atoms also include their branched isomers, such as, for example, the isopropyl, tert-butyl, isobutyl group, unless stated otherwise.

Particularly preferred compounds of the general formula I are those in which
X is an oxygen atom,
R ₁ and R ₅ each represent a hydrogen atom,
R _{2 is} a hydrogen, fluorine, chlorine or bromine atom,
a cyano group or
a carboxyC _1-2 alkoxycarbonyl, allyloxycarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 alkyl) aminocarbonyl group
R _{3 is} a 2-pyrrolyl-, 2-furyl-, 3-furyl-, 2-thienyl-, 3-thienyl-, 4-imidazolyl-, 5- (C _1-3 -alkyl) -pyrazol-3-yl- , 5- (C _1-3 alkyl) isoxazol-3-yl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 4-pyridazinyl, benzimidazol-5-yl, 1- (C _1-3- alkyl) -benzimidazol-5-yl-, 2- (C _1-3 -alkyl) -benzimidazol-5-yl-, 3,4-methylenedioxy-1-phenyl, 3,4-ethylenedioxy-1- phenyl-, 3,4- (difluoromethylenedioxy) -1-phenyl-, 2- (C _1-3 -alkyl) -isoindol-1,3-dione-5-yl-, quinoxalin-6-yl- or 1- ( C _1-3 alkyl) benzotriazol-5-yl group,
R _{4 is} a phenyl group substituted by the group R ₆ in the 3- or 4-position, which in the remaining 3- or 4-position additionally by a fluorine or chlorine atom or by a (C _1-3 ) alkoxy or Cyano group can be substituted, wherein
R _{6 is} a 1- (C _1-3 alkyl) imidazol-2-yl group,
a 5- (C _1-3 -alkyl) -pyrazol-1-yl group which can additionally be substituted in the 3-position by a C _1-3 -alkyl group,
a pyrrolid-2-one-1-yl group,
a terminally substituted by the group R ₇ C _1-2 alkyl group, wherein
R _{7 is} an amino, allylamino, C _1-4 alkylamino or di (C _1-3 alkyl) amino group, an ω-hydroxy-C ₂ _ ₃ -alkylamino, N- (C _{1 -3-} alkyl) -ω-hydroxy-C ₂ _ ₃ -alkyl-amino-, ω- (C _1-3 -alkoxy) -C _2-3 -alkyl-amino- or N- (C _1-3 -alkyl) ) - [ω- (C _1-3 alkoxy) -C _2-3 alkyl] amino group,
a pyridylamino group,
a 5- to 7-membered cycloalkyleneimino group in which
a carbon atom can be substituted by a hydroxyl or hydroxymethyl group, the substitution by a hydroxyl group on a carbon atom adjacent to the nitrogen atom being excluded,
a 6- to 7-membered cycloalkyleneimino group in which the methylene group in the 4-position can be replaced by an oxygen atom or an -NH-, -N- (allyl) or -N (C _1-3 -alkyl) group, or
a triazolyl group bonded via the nitrogen atom in the 1-position or 2-position,
or R _{6 is} a group of the formula - (CH ₂ ) _n -CO-R ₈ in the
R _{8 is} pyrrolidino, 2,5-dihydro-pyrrol-1-yl, piperidino, morpholino, thiomorpholino or a piperazino or perhydro-1,4 which is optionally substituted in the 4-position by a C _1-3 alkyl group -diazepinogruppe
and n is one of the numbers 0 or 1,
a group of the formula -CO-NR ₉ R ₁₀ in the
R _{9 is} a hydrogen atom, an allyl group or a C _1-3 alkyl group which is optionally terminally substituted by a cyano group and
R _{10 is} a hydrogen atom,
a C _1-3 alkyl group,
a C _2-3 alkyl group terminally substituted by a C _1-3 alkylamino or di (C _1-3 alkyl) amino group or
is a 3- to 7-membered cycloalkyl group in which a methylene group can be replaced by a -NH or -N (C _1-3 alkyl) group
a group of the formula -N (R ₁₅ ) -CO- (CH ₂ ) _s -R ₁₆ , in the
R _{15 is} a hydrogen atom, an allyl, C _1-3 alkyl, pyridinyl, ω - [(C _1-3 alkyl) amino] -C _{2 -3} alkyl or ω- [Di- (C _1-3 alkyl) amino] -C _{2 -3} alkyl group,
s one of the numbers 0, 1 or 2 and
R _{16 is} a C _1-3 alkoxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or pyridinyl group,
a pyrrolidino, 2,5-dihydropyrrol-1-yl, piperidino, morpholino or thiomorpholino group or
a piperazino or perhydro-1,4-diazepino group optionally substituted in the 4-position by a C _1-3 alkyl group
or, if s represents the number 1 or 2, also denote a hydrogen atom,
a group of the formula -N (R ₁₇ ) -SO ₂ -R ₁₈ , in the
R _{17 is} a hydrogen atom,
a C _1-3 alkyl group or
a C _2-3 alkyl group terminally substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group and
R _{18 represents} a C _1-3 alkyl group,
a group of the formula -SO ₂ - (CH ₂ ) _t -R ₁₉ , in the
t one of the numbers 1, 2 or 3 and
R _{19 represents} a hydrogen atom or, if n represents one of the numbers 2 or 3, also a di (C _1-3 alkyl) amino group,
or a group of the formula -O- (CH ₂ ) _t -R ₁₉ in the
t one of the numbers 1, 2 or 3 and
R _{19 represents} a hydrogen atom or, if n represents one of the numbers 2 or 3, also a di (C _1-3 alkyl) amino group,
or a group of the formula -SO ₂ -NR ₂₀ R ₂₅ , in the
R _{20 is} a hydrogen atom or an allyl or C _1-3 alkyl group and
R _{25 is} a C _1-3 alkyl group or
is a C _2-3 alkyl group substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group,
mean,
wherein the dialkylamino groups contained in the abovementioned radicals can contain two identical or two different alkyl groups and the saturated alkyl and alkoxy parts which contain more than 2 carbon atoms and which contain more than 2 carbon atoms can be linear or branched, unless stated otherwise,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

Very particularly preferred compounds of the general formula I are those in which
X is an oxygen atom,
R ₁ and R ₅ each represent a hydrogen atom,
R _{2 represents} a hydrogen, fluorine or chlorine atom or a methoxycarbonyl, ethoxycarbonyl, dimethylaminocarbonyl, N-ethyl-N-methyl-aminocarbonyl or diethylaminocarbonyl group,
R _{3 is} 3,4-methylenedioxy-1-phenyl-, 3,4-ethylenedioxy-1-phenyl-, quinoxalin-6-yl-, benzimidazol-5-yl-, 2-methylbenzimidazol-5-yl- or 1 -Methyl-benzimidazol-5-yl group and
R _{4 is} a phenyl group substituted in the 4-position by the group R ₆ , which may additionally be substituted in the 3-position by a fluorine or chlorine atom or a methoxy group, where
R _{6 is} a 1- (C _1-2 alkyl) imidazol-2-yl group,
a 3,5-dimethyl-pyrazol-1-yl group,
a pyrrolid-2-one-1-yl group,
a methyl group substituted by the group R ₇ , where
R _{7 is} a methylamino, ethylamino, isobutylamino, a di (C _1-2 alkyl) amino, N (2-hydroxyethyl) methylamino or N- (2-methoxyethyl) methylamino group,
a pyrrolidino, 3-hydroxypyrrolidino, 2-hydroxymethyl-pyrrolidino, 4-hydroxypiperidino, morpholino, piperazin-1-yl or 1-methyl-piperazin-4-yl group or
a 1,2,4-triazol-1-yl, 1,2,3-triazol-1-yl or 1,2,3-triazol-2-yl group,
or R _{6 is} an N-acetyl-methylamino or N-methoxyacetyl-methylamino group;
a group of the formula -CO-R ₈ , in the
R _{8 represents} a piperazino or perhydro-1,4-diazepino group which is optionally substituted by a methyl group in the 4-position,
a 4-methyl-piperazin-1-yl-carbonyl-methyl group,
a group of the formula -CO-NR ₉ R ₁₀ in the
R _{9 is} a methyl, cyanomethyl or ethyl group and
R _{10 represents} a methyl, 1-methylpiperidin-4-yl, 2-methylamino-ethyl, 2-dimethylamino-ethyl or 3-dimethylamino-propyl group
a group of the formula -N (R ₁₅ ) -CO- (CH ₂ ) _s -NMe ₂ , in the
s one of the numbers 1 or 2 and
R _{15 represents} a methyl or ethyl group or, if n represents the number 2, also a 3-pyridyl group,
a group of the formula -N (R ₁₅ ') -CO- (CH ₂ ) sH, in the
s one of the numbers 1 or 2 and
R ₁₅ 'represents a 2- (dimethylamino) ethyl or 3- (dimethylamino) propyl group,
or a group of the formula -N (Me) -CO- (CH ₂ ) _s -R ₁₆ ', in the
s one of the numbers 1 or 2 and
R ₁₆ 'is a dimethylamino group, or, if s represents the number 1, also a 4- (C _1-2 alkyl) piperazin-1-yl group,
a group of the formula -N (R ₁₇ ) -SO ₂ -R ₁₈ , in which a) R _{17 is} a dimethylaminoethyl group and R _{18 is} a methyl, ethyl or propyl group or
in which b) R ₁₇ and R ₁₈ each represent a methyl group,
a group of the formula -SO ₂ -N (R ₂₀ ) - (CH ₂ ) _u -NMe ₂ , in the
R _{20 represents} a hydrogen atom or a methyl group and
u is one of the numbers 2 or 3,
a group of the formula -SO ₂ -R ₂₆ , in the
R _{26 represents} a methyl group or a 2-di (C _1-2 alkyl) aminoethyl group,
or a 2-di- (C _1-2 -alkyl) -amino-ethoxy group,
the dialkylamino groups contained in the abovementioned radicals can contain two identical or two different alkyl groups,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

• (a) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (b) 3-(Z)-{1-(4-[N-Methyl-N-(4-methylpiperazin-1-yl-methylcarbonyl)-amino]-phenylamino)-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (c) 3-(Z)-{1-[4-(N-Ethyl-N-methyl-aminomethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (d) 3-(Z)-{1-[4-(N-Methyl-N-{2-(dimethylamino)-ethyl-carbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (e) 3-(Z)-{1-[4-(1,2,4-Triazol-1-yl-methyl)-phenylamino]-1-(1-methyl-benzimidazol-5-yl)-methylen}-6-fluor-2-indolinon
• (f) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(1-methyl-benzimidazol-5-yl)-methylen}-6-chlor-2-indolinon
• (g) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (h) 3-(Z)-{1-(4-[N-Methansulfonyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (i) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (j) 3-(Z)-{1-(4-[N-Methyl-N-(4-methylpiperazin-1-yl-methylcarbonyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (k) 3-(Z)-{1-(4-[N-Acetyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (l) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (m) 3-(Z)-{1-(4-[N-Acetyl-N-(3-dimethylaminopropyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (n) 3-(Z)-{1-(4-[N-Propionyl-N-(3-dimethylaminopropyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (o) 3-(Z)-{1-(4-[N-Propionyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (p) 3-(Z)-{1-(4-[N-Acetyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (q) 3-(Z)-{1-(4-[4-Methylpiperazin-1-yl-methyl]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• s(r) 3-(Z)-{1-(4-[N-Methansulfonyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (s) 3-(Z)-{1-(4-[Pyrrolidin-1-yl-methyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (t) 3-(Z)-{1-(4-[N-Methyl-N-(dimethylaminomethylcarbonyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (u) 3-(Z)-{1-(4-[Ethylamino-methyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methaxycarbonyl-2-indolinon
• (v) 3-(Z)-{1-(4-[4-Methylpiperazin-1-yl-methyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (w) 3-(Z)-{1-(4-[Dimethylamino-methyl]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (x) 3-(Z)-{1-(4-[Diethylamino-methyl]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (y) 3-(Z)-{1-[4-(Dimethylaminocarbonyl)-phenylamino]-1-(1-methyl-benzimidazol-5-yl)-methylen}-6-fluor-2-indolinon
• (z) 3-(Z)-{1-(4-[N-Propionyl-N-(3-dimethylaminopropyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (aa) 3-(Z)-{1-(4-[N-Propionyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (ab) 3-(Z)-{1-(4-[N-Methansulfonyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (ac) 3-(Z)-{1-(4-[N-Acetyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (ad) 3-(Z)-{1-(4-[N-Methyl-N-(2-dimethylaminoethyl)aminocarbonyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (ae) 3-(Z)-{1-(4-[N-Methyl-N-(3-dimethylaminopropyl)aminocarbonyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (af) 3-(Z)-{1-(4-[N-Methyl-N-(2-dimethylaminoethyl)aminocarbonyl]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon und
• (az) 3-(Z)-{1-(4-[N-Methyl-N-(4-methylpiperazin-1-yl-methylcarbonyl)-amino]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon,

deren Tautomere und deren Salze. The following are particularly preferred compounds:

• (a) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-chloro-2-indolinone
• (b) 3- (Z) - {1- (4- [N-Methyl-N- (4-methylpiperazin-1-yl-methylcarbonyl) amino] phenylamino) -1- (quinoxalin-6-yl) - methylene} -6-chloro-2-indolinone
• (c) 3- (Z) - {1- [4- (N-Ethyl-N-methylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-chloro-2-indolinone
• (d) 3- (Z) - {1- [4- (N-Methyl-N- {2- (dimethylamino) ethylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) - methylene} -6-fluoro-2-indolinone
• (e) 3- (Z) - {1- [4- (1,2,4-Triazol-1-yl-methyl) -phenylamino] -1- (1-methyl-benzimidazol-5-yl) -methylene} -6-fluoro-2-indolinone
• (f) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (1-methyl-benzimidazol-5-yl) -methylene} -6-chloro-2-indolinone
• (g) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-chloro-2-indolinone
• (h) 3- (Z) - {1- (4- [N-methanesulfonyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-chlorine -2-indolinone
• (i) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (j) 3- (Z) - {1- (4- [N-Methyl-N- (4-methylpiperazin-1-yl-methylcarbonyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) - methylene} -6-methoxycarbonyl-2-indolinone
• (k) 3- (Z) - {1- (4- [N-Acetyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluoro -2-indolinone
• (l) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluoro-2-indolinone
• (m) 3- (Z) - {1- (4- [N-Acetyl-N- (3-dimethylaminopropyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-chloro -2-indolinone
• (n) 3- (Z) - {1- (4- [N-Propionyl-N- (3-dimethylaminopropyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-chlorine -2-indolinone
• (o) 3- (Z) - {1- (4- [N-Propionyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-chlorine -2-indolinone
• (p) 3- (Z) - {1- (4- [N-Acetyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-chloro -2-indolinone
• (q) 3- (Z) - {1- (4- [4-Methylpiperazin-1-ylmethyl] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -6-chloro-2-indolinone
• s (r) 3- (Z) - {1- (4- [N-methanesulfonyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6- methoxycarbonyl-2-indolinone
• (s) 3- (Z) - {1- (4- [Pyrrolidin-1-ylmethyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (t) 3- (Z) - {1- (4- [N-Methyl-N- (dimethylaminomethylcarbonyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2 -indolinon
• (u) 3- (Z) - {1- (4- [Ethylamino-methyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methaxycarbonyl-2-indolinone
• (v) 3- (Z) - {1- (4- [4-Methylpiperazin-1-ylmethyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (w) 3- (Z) - {1- (4- [Dimethylamino-methyl] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (x) 3- (Z) - {1- (4- [Diethylamino-methyl] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (y) 3- (Z) - {1- [4- (Dimethylaminocarbonyl) phenylamino] -1- (1-methyl-benzimidazol-5-yl) -methylene} -6-fluoro-2-indolinone
• (z) 3- (Z) - {1- (4- [N-Propionyl-N- (3-dimethylaminopropyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluorine -2-indolinone
• (aa) 3- (Z) - {1- (4- [N-Propionyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluoro -2-indolinone
• (ab) 3- (Z) - {1- (4- [N-methanesulfonyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluorine -2-indolinone
• (ac) 3- (Z) - {1- (4- [N-acetyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl -2-indolinone
• (ad) 3- (Z) - {1- (4- [N-methyl-N- (2-dimethylaminoethyl) aminocarbonyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl- 2-indolinone
• (ae) 3- (Z) - {1- (4- [N-Methyl-N- (3-dimethylaminopropyl) aminocarbonyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) -methylene} -6-methoxycarbonyl-2-indolinone
• (af) 3- (Z) - {1- (4- [N-Methyl-N- (2-dimethylaminoethyl) aminocarbonyl] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -6-methoxycarbonyl- 2-indolinone and
• (az) 3- (Z) - {1- (4- [N-Methyl-N- (4-methylpiperazin-1-yl-methylcarbonyl) amino] phenylamino) -1- (3,4-methylenedioxyphenyl) - methylene} -6-chloro-2-indolinone,

their tautomers and their salts.

According to the invention, the new compounds are obtained for example according to the following processes which are known in principle from the literature:

in der
X und R₃ wie eingangs erwähnt definiert sind,
R₂' die für R₂ eingangs erwähnten Bedeutungen besitzt,
R₂₇ ein Wasserstoffatom oder eine Schutzgruppe für das Stickstoffatom der Lactamgruppe, wobei einer der Reste R₂' und R₂₇ auch eine gegebenenenfalls über einen Spacer gebildete Bindung an eine Festphase darstellen kann und der andere der Reste R₂' und R₂₇ die vorstehend erwähnten Bedeutungen besitzt, und Z₁ ein Halogenatom, eine Hydroxy-, Alkoxy- oder Aryl-alkoxygruppe, z.B. ein Chlor- oder Bromatom, eine Methoxy-, Ethoxy- oder Benzyloxygruppe, bedeuten,
mit einem Amin der allgemeinen Formel

in der
R₄ und R₅ wie eingangs erwähnt definiert sind, und erforderlichenfalls anschließende Abspaltung einer verwendeten Schutzgruppe für das Stickstoffatom der Lactamgruppe oder von einer Festphase.a. Implementation of a compound of the general formula

in the
X and R ₃ are defined as mentioned at the beginning,
R ₂ 'has the meanings mentioned above for R ₂ ,
R _{27 is} a hydrogen atom or a protective group for the nitrogen atom of the lactam group, it being possible for one of the radicals R ₂ 'and R _{27 to} also represent a bond to a solid phase which may be formed via a spacer and the other of the radicals R ₂ ' and R _{27 to be} those mentioned above Has meanings, and Z _{1 represents} a halogen atom, a hydroxyl, alkoxy or arylalkoxy group, for example a chlorine or bromine atom, a methoxy, ethoxy or benzyloxy group,
with an amine of the general formula

in the
R ₄ and R ₅ are defined as mentioned at the beginning, and if necessary subsequent cleavage of a protective group used for the nitrogen atom of the lactam group or from a solid phase.

A protective group for the nitrogen atom of the lactam group is, for example, an acetyl, benzoyl, ethoxycarbonyl, tert.butyloxycarbonyl or benzyloxycarbonyl group and
as a solid phase, a resin such as a 4- (2 ', 4'-dimethoxyphenylaminomethyl) phenoxy resin, where the binding is advantageously carried out via the amino group, or a p-benzyloxybenzyl alcohol resin, the binding advantageously via an intermediate member such as a 2,5-dimethoxy 4-hydroxy-benzyl derivative is considered.

The implementation will be convenient in a solvent such as dimethylformamide, toluene, acetonitrile, tetrahydrofuran, dioxane, Methanol, ethanol, 2-propanol, dimethyl sulfoxide, methylene chloride or mixtures thereof, if appropriate in the presence of an inert base such as triethylamine, N-ethyl-diisopropylamine or sodium hydrogen carbonate carried out at temperatures between 20 and 175 ° C, with a protective group used can be split off simultaneously as a result of transamidation.

If Z ₁ in a compound of the general formula II denotes a halogen atom, the reaction is preferably carried out in the presence of an inert base at temperatures between 20 and 120 ° C.

Means Z, in a compound of general formula II a hydroxy, alkoxy or arylalkoxy group, then the Reaction preferably carried out at temperatures between 20 and 200 ° C.

The subsequent splitting off of a protective group that may be required is expediently carried out either hydrolytically in an aqueous or alcoholic solvent, for example in Me thanol / water, ethanol / water, isopropanol / water, tetrahydrofuran / water, dioxane / water, dimethylformamide / water, methanol or ethanol in the presence of an alkali 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 mixtures thereof or in an excess of the amine used at temperatures between 0 and 100 ° C, preferably carried out at temperatures between 10 and 50 ° C.

The split off from one used Solid phase is preferably carried out using trifluoroacetic acid and water at temperatures between 0 and 35 ° C, preferably at room temperature.

b. For the preparation of a compound of general formula I in which
R _{2 is} a linear or branched C _1-6 alkoxycarbonyl group, a C _3-6 cycloalkoxycarbonyl or an aryloxycarbonyl group,
an allyloxycarbonyl group optionally substituted by one or two methyl groups,
a linear or branched C _1-3 alkoxy-carbonyl group which is terminated in the alkyl part by a phenyl, heteroaryl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino-carbonyl or di (C _1-3 alkyl) aminocarbonyl group is substituted,
a linear or branched C _2-6 alkoxy carbonyl group which is terminated in the alkyl part by a chlorine atom or a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _{1- 3} -alkyl) -amino group is substituted, or
an aminocarbonyl, C _1-3 alkyl aminocarbonyl or a di (C _1-4 alkyl) aminocarbonyl group, the alkyl groups, if they have more than one carbon atom, terminated by a hydroxy, C _1-3 Alkoxy or di- (C _1-3 alkyl) amino group can be substituted means:

in der
X, R₁ und R₃ bis R₅ wie eingangs erwähnt definiert sind, oder deren reaktionsfähigen Derivaten mit einer Verbindung der allgemeinen Formel H–R₂₈ (V),in der
R₂₈ ein linearer oder verzweigter C_1-6-Alkanol, ein C_3-6-Cycloalanol oder ein aromatischer Alkohol,
ein gegebenenfalls durch eine oder zwei Methylgruppen substituierter Allyl-akohol,
ein linearer oder verzweigter C_1-4-Alkanol, der im Alkylteil terminal durch eine Phenyl-, Heteroaryl-, Carboxy-, C_1-3-Alkoxy-carbonyl-, Aminocarbonyl-, C_1-3-Alkylamino-carbonyl- oder Di-(C_1-3-alkyl)-aminocarbonylgruppe substituiert ist,
eine linearer oder verzweigter C_2-6-Alkanol, der im Alkylteil terminal durch ein Chloratom oder eine Hydroxy-, C_1-3-Alkoxy-, Amino-, C_1-3-Alkylamino- oder Di-(C_1-3-alkyl)-aminogruppe substituiert ist, oder
eine Amino-, C_1-4-Alkyl-amino- oder eine Di-(C_1-4-alkyl)-aminogruppe, wobei die Alkylgruppen, sofern sie mehr als ein Kohlenstoffatom besitzen, terminal durch eine Hydroxy-, C_1-3-Alkoxy- oder Di-(C_1-3-alkyl)-aminogruppe substituiert sein können, bedeutet.Implementation of a compound of the general formula

in the
X, R ₁ and R ₃ to R ₅ are defined as mentioned at the outset, or their reactive derivatives with a compound of the general formula H – R ₂₈ (V), in the
R _{28 is} a linear or branched C _1-6 alkanol, a C _3-6 cycloalanol or an aromatic alcohol,
an allyl alcohol optionally substituted by one or two methyl groups,
a linear or branched C _1-4 alkanol, which is terminated in the alkyl part by a phenyl, heteroaryl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino carbonyl or di - (C _1-3 alkyl) aminocarbonyl group is substituted,
a linear or branched C _2-6 alkanol which is terminated in the alkyl part by a chlorine atom or a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _1-3 - alkyl) amino group is substituted, or
an amino, C _1-4 alkylamino or a di (C _1-4 alkyl) amino group, where the alkyl groups, if they have more than one carbon atom, are terminated by a hydroxy, C _1-3 -Alkoxy- or di- (C _1-3 alkyl) amino group may be substituted.

The esterification or amidation is preferably carried out in a solvent such as methylene chloride, diethyl ether, tetrahydrofuran, toluene, dioxane, acetonitrile, dimethyl sulfoxide or dimethylformamide, optionally in the presence of an inorganic or a tertiary organic base, preferably at temperatures between 20 ° C. and the boiling point of the solvent used, carried out. Here, the reaction with a corresponding acid is preferably carried out in the presence of a dehydrating agent, for example in the presence of isobutyl chloroformate, tetraethyl orthocarbonate, trimethyl orthoacetic acid, 2,2-dimethoxypropane, tetramethoxysilane, thionyl chloride, trimethylchlorosilane, phosphorus trichloride, nodophenyl dodicyclide, phosphorus pentoxide, phosphorus pentoxide, phosphorus pentoxide, N'-dicyclohexylcarbodiimide / N-hydroxysuccinimide, N, N'-dicyclohexylcarbodiimide / 1-hydroxy-benzotriazole, 2- (1H-benzotriazol-1-yl) -1,1,3,3-tetramethyluronium te trafluoroborate, 2- (1H-benzotriazol-1-yl) -1,1,3,3-tetramethyluronium tetrafluoroborate / 1-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 expediently 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 its anhydride, ester, imidazolides or halides optionally in 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.

in der
X, R₁, R₂, R₄ und R₅ wie eingangs erwähnt definiert sind und
R_a und R_b jeweils unabhängig voneinander ein Wasserstoffatom, eine C_1-3-Alkylgruppe oder eine Carboxy-C_1-3-alkylgruppe sein können:c. For the preparation of a compound of the general formula

in the
X, R ₁ , R ₂ , R ₄ and R ₅ are defined as mentioned at the beginning and
R _a and R _{b can} each independently be a hydrogen atom, a C _1-3 alkyl group or a carboxy-C _1-3 alkyl group:

in der
X, R₁, R₂, R₄ und R₅ wie eingangs erwähnt definiert sind und
R_a ein Wasserstoffatom, eine C_1-3-Alkylgruppe oder eine gegebenenfalls geschützte Carboxy-C_1-3-alkylgruppe sein kann,
mit Wasserstoff (1-10 bar) oder einem Reagens zur Transferhydrierung, wie beispielsweise Cyclohexen, 1,3-Cyclohexadien oder Ammoniumformiat in Anwesenheit eines Hydrierkatalysators wie beispielsweise Raney-Nickel oder Palladium auf Aktivkohle bei Temperaturen von 0°C bis 150 °C, bevorzugt bei 10 °C bis zur Siedetemperatur des Lösungsmittels bzw. -gemisches,
entweder
c1. in Ameisensäure, gegebenenfalls unter Verwendung eines Kosolvens, wobei man Verbindungen der allgemeinen Formel VIa bzw. VIb erhält, in denen
R_b ein Wasserstoffatom und
R_a ein Wasserstoffatom, eine C_1-3-Alkylgruppe oder eine gegebenenfalls geschützte Carboxy-C_1-3-alkylgruppe ist.
oder
c2. in einem Lösungsmittel wie beispielsweise Essigsäure, Propionsäure, Methanol, Ethanol oder Mischungen derselben untereinander oder mit anderen Lösungmitteln wie beispielweise Essigester, THF oder Dioxan,
wobei man Verbindungen der allgemeinen Formel I erhält, in denen R₃ ein an einer der Aminogruppen mit R_a substituierter 3,4-Diaminophenylrest ist,
welche weiter umgesetzt werden
in R_b-COOH oder, falls R_b eine Carboxyalkylgruppe ist, auch einem geschützten Derivat wie einem entsprechenden Halbester, als Solvens und Reaktant oder gegebenenfalls – insbesondere, wenn R_b-COOH bei der gewählten Reaktionstemperatur ein Feststoff ist – unter Zusatz eines Lösungsmittels wie beispielsweise Methanol, Ethanol, 2-Propanol, Essigsäure, Propionsäure, THF, Dioxan, Dichlormethan oder Essigester bei Temperaturen von 10 °C – 150 °C, bevorzugt bei 20 °C bis zum Siedepunkt des Lösungsmittels bzw. -gemisches zu Verbindungen der allgemeinen Formel VIa bzw. VIb in denen
R_a und R_b unabhängig voneinander ein Wasserstoffatom, eine C_1-3-Alkylgruppe oder eine gegebenenfalls geschützte Carboxy-C_1-3-alkylgruppe sein können.Reduction of a compound of the general formula

in the
X, R ₁ , R ₂ , R ₄ and R ₅ are defined as mentioned at the beginning and
R _{a can be} a hydrogen atom, a C _1-3 alkyl group or an optionally protected carboxy-C _1-3 alkyl group,
with hydrogen (1-10 bar) or a reagent for transfer hydrogenation, such as, for example, cyclohexene, 1,3-cyclohexadiene or ammonium formate in the presence of a hydrogenation catalyst such as, for example, Raney nickel or palladium on activated carbon at temperatures from 0 ° C. to 150 ° C., are preferred at 10 ° C to the boiling point of the solvent or mixture,
either
c1. in formic acid, optionally using a cosolvent, to give compounds of the general formula VIa or VIb in which
R _{b is} a hydrogen atom and
R _{a is} a hydrogen atom, a C _1-3 alkyl group or an optionally protected carboxy-C _1-3 alkyl group.
or
c2. in a solvent such as, for example, acetic acid, propionic acid, methanol, ethanol or mixtures thereof with one another or with other solvents such as, for example, ethyl acetate, THF or dioxane,
to obtain compounds of the general formula I in which R _{3 is} a 3,4-diaminophenyl radical substituted on one of the amino groups with R _a ,
which will continue to be implemented
in R _b -COOH or, if R _{b is} a carboxyalkyl group, also a protected derivative such as a corresponding half-ester, as solvent and reactant or optionally - in particular if R _b -COOH is a solid at the chosen reaction temperature - with the addition of a solvent such as for example methanol, ethanol, 2-propanol, acetic acid, propionic acid, THF, dioxane, dichloromethane or ethyl acetate at temperatures of 10 ° C - 150 ° C, preferably at 20 ° C to the boiling point of the solvent or mixture to give compounds of the general formula VIa and VIb in which
R _a and R _{b can} independently of one another be a hydrogen atom, a C _1-3 alkyl group or an optionally protected carboxy-C _1-3 alkyl group.

in der
R₃, R₅ und X wie eingangs erwähnt definiert sind,
R₂' die für R₂ eingangs erwähnten Bedeutungen besitzt,
R₂₇ ein Wasserstoffatom oder eine Schutzgruppe für das Stickstoffatom der Lactamgruppe, wobei einer der Reste R₂' und R₂₇ auch eine gegebenenenfalls über einen Spacer gebildete Bindung an eine Festphase darstellen kann und der andere der Reste R₂' und R₂₇ die vorstehend erwähnten Bedeutungen besitzt,
A eine C_1-3-Alkylgruppe und
Z₂ eine Austrittsgruppe, beispielsweise eine Alkyl- oder Arylsulfonyloxygruppe wie die Methylsulfonyloxy-, Ethylsulfonyloxy-, p-Toluolsulfonyloxy-, oder Trifluormethansulfonyloxygruppe darstellt, mit einem Amin der allgemeinen Formel H–R_7' (IX),in der
R_7' die vorstehend für R₇ genannten Bedeutungen besitzt, und erforderlichenfalls anschließende Abspaltung einer verwendeten Schutzgruppe für das Stickstoffatom der Lactamgruppe oder von einer Festphase.d. For the preparation of a compound of the general formula I in which R _{4 represents} a phenyl group which is substituted by the group R ₆ in the 3 or 4 position and which can additionally be substituted as described above, and R _{6 is} a C ₁ substituted by R _{7 -3-} alkyl group means, wherein
R _{7 is} a heteroaryl group which is bonded via an imino nitrogen, a hydroxy or C _1-3 alkoxy group,
an amino, C _1-7 alkylamino, di (C _1-7 alkyl) amino, N- (C _1-7 alkyl) allylamino, phenylamino, N-phenyl-C _{1- 3-} alkyl-amino-, phenyl-C _1-3 -alkylamino-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino- or di- (phenyl-C _1-3 -alkyl) amino group,
an allylamino group in which one or two vinyl hydrogen atoms can each be replaced by a methyl group,
a ω-hydroxy-C _2-3 -alkyl-amino-, N- (C _1-3 -alkyl) -ω-hydroxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _{2- 3} -alkyl) -amino-, N- (C _1-3 -alkyl) - [ω- (C _1-3 -alkoxy) -C _2-3 -alkyl] amino-, di- (ω- (C _{1- 3} alkoxy) C _{2- 3} alkyl) -amino or N- (dioxolan-2-yl) -C _1-3 alkyl-amino group,
a C _1-3 -alkyl-carbonylamino-C ₂ _ ₃ alkyl-amino or C _1-3 -alkyl-carbonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
a pyridylamino group,
a C _1-3 -alkylsulfonylamino-, N- (C _1-3 -alkyl) -C _1-3 -alkylsulfonylamino-, C _1-3 -alkylsulfonylamino-C _2-3 -alkyl-amino- or C _1-3 - Alkylsulfonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
a hydroxycarbonyl-C _1-3 -alkylamino- or N- (C _1-3 -alkyl) -hydroxycarbonyl-C _1-3 -alkyl-amino group,
a guanidino group in which one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group,
a 2-pyrrolidon-1-yl group in which the methylene group adjacent to the carbonyl group can be replaced by an oxygen atom or by an -NH or -N (C _1-3 -alkyl) group,
a group of the formula -N (R ₂₂ ) -CO- (CH ₂ ) _p -R ₁₂ , in the
R _{11 is} a hydrogen atom or an allyl, C _1-3 alkyl, C _1-3 alkyl amino C _2-3 alkyl or di (C _1-3 alkyl) amino C _{2- 3} -alkyl group,
p is one of the numbers 0, 1, 2 or 3 and
R _{12 is} an amino, C _1-4 alkylamino, allylamino, di-allyl amino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-4 alkyl) ) phenylamino, benzylamino, N- (C _1-4 alkyl) benzylamino, C _1-4 alkoxy or 2,5-dihydropyrrol-1-yl group or
a 4- to 7-membered cycloalkyleneimino group,
where in each case the methylene group in position 4 of a 6 or 7-membered cycloalkyleneimino group is represented by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl) -, -N (allyl ) -, -N (phenyl) -, -N (C _1-3 alkylcarbonyl) - or -N (benzoyl) - group can be replaced,
or, if n represents one of the numbers 1, 2 or 3, also denote a hydrogen atom,
a group of the formula -N (R ₁₃ ) - (CH ₂ ) _q - (CO) _r -R ₁₄ in the
R _{13 is} a hydrogen atom or a C _1-3 alkyl, allyl, C _1-3 alkyl carbonyl, arylcarbonyl, pyridylcarbonyl, phenyl C _1-3 alkyl carbonyl, C _1-3 - Alkylsulfonyl, arylsulfonyl or phenylC _1-3 alkylsulfonyl group,
q one of the numbers 1, 2, 3 or 4,
r the number 1 or, if q is one of the numbers 2, 3 or 4, also the number 0 and
R _{14 is} hydroxy, amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino , N- (C _1-4 alkyl) benzylamino, C _1-4 alkoxy or C _1-3 alkoxy-C _1-3 alkoxy group,
a di- (C _1-4 -alkyl) -amino-C _1-3 -alkylamino group which is optionally substituted in the 1-position by a C _1-3 alkyl group or
a 4- to 7-membered cycloalkyleneimino group,
wherein the cycloalkylene part can be condensed with a phenyl ring or
each the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group through an oxygen or sulfur atom, through a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl) -, -N (phenyl) -, -N (C _1-3 - alkyl-carbonyl) - or -N (benzoyl) - group can be replaced, mean
a C _4-7 cycloalkylamino, C _4-7 cycloalkyl-C _1-3 alkylamino or C _4-7 cycloalkenylamino group in which position 1 of the ring is not involved in the double bond and wherein the groups mentioned above can each additionally be substituted on the amine nitrogen atom by a C _5-7 cycloalkyl, C _2-4 alkenyl or C _1-4 alkyl group,
a 2,5-dihydro-pyrrol-1-yl group or
a 4- to 7-membered cycloalkyleneimino group in which
the cycloalkylene part with a phenyl group or with an oxazolo, imidazolo, optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, C _1-3 alkyl, C _1-3 alkoxy or amino group , Thiazolo, pyridino, pyrazino or pyrimidino group can be condensed or / and
one or two hydrogen atoms each through a C _1-3 alkyl, C _3-7 cycloalkyl, hydroxy, C _1-3 alkoxy, hydroxy C _1-3 alkyl or C _1-3 alkoxy -C _1-3 alkyl or phenyl group can be replaced or / and
the methylene group in position 3 of a 5-membered cycloalkyleneimino group can be substituted by a hydroxy, hydroxyC _1-3 alkyl, C _1-3 alkoxy or C _1-3 alkoxyC _1-3 alkyl group,
each the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group by a hydroxy, hydroxyC _1-3 alkyl, C _1-3 alkoxy, C _1-3 alkoxyC _1-3 -alkyl-, carboxy-, C _1-4 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocarbonyl-, di- (C _1-3 -alkyl) -aminocarbonyl-, phenyl-C _1-3 - alkylamino- or N- (C _1-3 alkyl) phenyl-C _1-3 alkylamino group substituted or
the methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl) -, -N (allyl) - , -N (phenyl) -, -N (phenyl-C _1-3 -alkyl) -, -N (C _1-3 -alkyl-carbonyl) -, -N (C _1-4 -hydroxy-carbonyl) -, -N (C _1-4 -alkoxy-carbonyl) -, -N (benzoyl) - or -N (phenyl-C _1-3 -alkyl-carbonyl) group can be replaced,
wherein a methylene group linked to an imino nitrogen atom of the cycloalkyleneimino group can be replaced by a carbonyl or sulfonyl group or in a 5- to 7-membered monocyclic or fused to a phenyl group cycloalkyleneimino group, both methylene groups linked to the imino nitrogen atom can each be replaced by a carbonyl group can,
means:
Implementation of a compound of the general formula

in the
R ₃ , R ₅ and X are defined as mentioned at the beginning,
R ₂ 'has the meanings mentioned above for R ₂ ,
R _{27 is} a hydrogen atom or a protective group for the nitrogen atom of the lactam group, it being possible for one of the radicals R ₂ 'and R _{27 to} also represent a bond to a solid phase which may be formed via a spacer and the other of the radicals R ₂ ' and R _{27 to be} those mentioned above Has meanings
A is a C _1-3 alkyl group and
Z _{2 represents} a leaving group, for example an alkyl or arylsulfonyloxy group such as the methylsulfonyloxy, ethylsulfonyloxy, p-toluenesulfonyloxy or trifluoromethanesulfonyloxy group, with an amine of the general formula HR _{7 '} (IX), in the
R _{7 'has} the meanings given above for R ₇ , and if necessary subsequent cleavage of a protective group used for the nitrogen atom of the lactam group or from a solid phase.

The reaction is conveniently carried out in a solvent such as methylene chloride, tetrahydrofu ran, 1,4-dioxane, toluene, acetonitrile, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, N-methylpyrrolidone or their mixtures, optionally with the addition of water as cosolvent or / and with the addition of an inert auxiliary base, for example 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-enes, at temperatures between -50 ° C and + 100 ° C, preferably between -10 ° C and + 50 ° C, wherein a protective group used can be split off due to transamidation at the same time.

The necessary, if necessary Removal of a protective group used for the nitrogen atom of the lactam group or from a solid phase as described above under Process (a).

If, according to the invention, a compound of the general formula I is obtained which contains an alkoxycarbonyl group, this can be converted into a corresponding carboxy compound by means of hydrolysis, or
a compound of the general formula I which contains an amino or alkylamino group, this can be converted into a corresponding alkylamino or dialkylamino compound by means of reductive alkylation, or
a compound of the general formula I which contains an amino or alkylamino group, this can be converted into a corresponding acyl or sulfonyl compound by means of acylation or sulfonation, or
a compound of the general formula I which contains a carboxy group, this can be converted into a corresponding ester or aminocarbonyl compound by esterification or amidation, or
a compound of the general formula I which contains a cycloalkyleneimino group in which a methylene group has been replaced by a sulfur atom, this can be converted into a corresponding sulfinyl or sulfonyl compound by oxidation, or
a compound of the general formula I which contains a nitro group, this can be converted into a corresponding amino compound by reduction, or
a compound of the general formula I in which R _{4 represents} a phenyl group substituted by an amino, alkylamino, aminoalkyl or N-alkylamino group, this can then be converted into a corresponding urea compound by reaction with a corresponding cyanate, isocyanate or carbamoyl halide of the general formula I are transferred or
a compound of the general formula I in which R _{4 represents} a phenyl group substituted by an amino, alkylamino, aminoalkyl or N-alkylamino group, this can then be reacted with a corresponding compound transferring the amidino group or by reaction with a corresponding nitrile can be converted into a corresponding guanidino compound of the 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 dioxane / water, in the presence of an acid such as trifluoroacetic, hydrochloric acid or sulfuric acid or in the presence of an alkali 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 in a suitable solvent such as methanol, methanol / water, Methanol / water / ammonia, ethanol, ether, tetrahydrofuran, dioxane or dimethylformamide, optionally with the addition of an acid such as hydrochloric acid in the presence of catalytically excited hydrogen, e.g. of hydrogen in the presence of Raney nickel, platinum or palladium / coal, or in Presence of a metal hydride such as sodium borohydride, lithium borohydride, Sodium cyanoborohydride or lithium aluminum hydride at temperatures between 0 and 100 ° C, preferably carried out at temperatures between 20 and 80 ° C.

The subsequent acylation or sulfonylation is advantageously carried out with the corresponding free acid or a corresponding reactive compound such as its anhydride, ester, imidazolide or halide, preferably in a solvent such as methylene chloride, diethyl ether, tetrahydrofuran, toluene, dioxane, acetonitrile, dimethyl sulfoxide or dimethylformamide, optionally in the presence of a inorganic or a tertiary organic base at temperatures between -20 and 200 ° C, preferably at temperatures between 20 ° C and the boiling point of the solvent used. The reaction with the free acid can, if appropriate, in the presence of an acid-activating agent or a dehydrating agent, for example in the presence of isobutyl chloroformate, tetraethyl orthocarbonate, trimethyl orthoacetate, 2,2-dimethoxypropane, tetramethoxysilane, thionyl chloride, trimethylchlorosilane, phosphorus pentichloride, phosphorus trichloride N'-dicyclohexylcarbodiimide, N, N'-dicyclohexylcarbodiimide / N-hydroxysuccinimide, N, N'-dicyclohexylcarbodiimide / 1-hydroxy-benzotriazole, 2- (1H-benzotriazol-1-yl) -1,1,3,3-tetramethyloronium tetra , 2- (1H-Benzotriazol-1-yl) -1,1,3,3-tetramethyluronium tetrafluoroborate / 1-hydroxy-benzotriazole, N, N'-carbonyldiimidazole or triphenylphosphine / carbon tetrachloride, and optionally with the addition of a base such as pyridine , 4-Dimethylamino-pyridine, N-methyl-morpholine or triethylamine expediently at temperatures between 0 and 150 ° C, preferably at temperatures between between 0 and 100 ° C. The reaction with a corresponding reactive compound can optionally in the presence of a tertiary organic base such as triethylamine, N-ethyl-diisopropylamine, N-methyl-morpholine or pyridine or when 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 will be convenient by implementing a responsive corresponding carboxylic acid derivative with an appropriate alcohol or amine as described above carried out.

The subsequent oxidation of the sulfur atom is preferably in a solvent or solvent mixture, e.g. in water, water / pyridine, acetone, methylene chloride, acetic acid, acetic acid / acetic anhydride, diluted sulfuric acid or trifluoroacetic acid, depending on the oxidizing agent used, expediently at temperatures between -80 and 100 ° C carried out.

To produce a corresponding The sulfinyl compound of the general formula I is advantageously the oxidation with an equivalent of the oxidizing 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 like performic acid in glacial acetic acid or trifluoroacetic acid at 0 to 50 ° C or with m-chloroperbenzoic acid in methylene chloride, chloroform or dioxane at -20 to 80 ° C, with sodium metaperiodate in aqueous methanol or ethanol at –15 up to 25 ° C, with bromine in glacial acetic acid or aqueous acetic acid if necessary 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 sulfuryl chloride in Methylene chloride at -70 ° C, which here obtained thioether-chlorine complex will be convenient with aqueous ethanol hydrolyzed.

To prepare a sulfonyl compound of the general formula I, the oxidation is based on a corresponding sulfinyl compound expediently with one or more equivalents of the oxidizing agent used or starting from a corresponding one Mercapto compound conveniently with two or more equivalents of the oxidizing agent used, e.g. with hydrogen peroxide in Glacial acetic acid / acetic anhydride, trifluoroacetic acid or in formic acid 20 to 100 ° C or in acetone at 0 to 60 ° C, with a peracid like 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 / sulfuric acid or in acetone at 0 to 20 ° C.

The subsequent reduction of a nitro group is preferably hydrogenolytic, e.g. with hydrogen in the presence a catalyst such as palladium / carbon or Raney nickel in one solvent such as methanol, ethanol, ethyl acetate, Dimethylformamide, dimethylformamide / acetone or glacial acetic acid if necessary with the addition of an acid like hydrochloric acid or glacial acetic acid at temperatures between 0 and 50 ° C, but preferably at room temperature, and at a hydrogen pressure of 1 to 7 bar, but preferably of 3 to 5 bar.

The subsequent production of a corresponding one Urea compound of general formula I is convenient with an inorganic cyanate or a corresponding isocyanate or carbamoyl chloride, 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 room temperature, carried out.

The subsequent production of a corresponding one Guanidino compound of general formula I is convenient by reaction with a compound transferring the amidino group, such as 3,5-dimethylpyrazole-1-carboxamide 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 room temperature.

In the above Implementations can optionally present reactive groups such as carboxy, hydroxy, Amino, alkylamino or imino groups during the reaction by conventional protective groups protected which are split off after the implementation.

For example, comes as a protective residue for one Carboxy group the trimethylsilyl, methyl, ethyl, tert-butyl, Benzyl or tetrahydropyranyl group and as a protective radical for a hydroxy, Amino, alkylamino or imino group, acetyl, trifluoroacetyl, Benzoyl, ethoxycarbonyl, tert.butoxycarbonyl, benzyloxycarbonyl, Benzyl, methoxybenzyl or 2,4-dimethoxybenzyl group and for the amino group additionally the phthalyl group into consideration.

The subsequent subsequent splitting, if applicable of a protective residue used is, for example, hydrolytic in an aqueous solvent, e.g. in water, isopropanol / water, tetrahydrofuran / water or Dioxane / water, in the presence of an acid such as trifluoroacetic acid, hydrochloric acid or sulfuric acid or in the presence of an alkali 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 cleavage of a benzyl, methoxybenzyl or benzyloxycarbonyl radical, for example, takes place hydrogenolytically, e.g. with hydrogen in the presence of a catalyst such as palladium / carbon in a solvent such as methanol, ethanol, ethyl acetate, Dimethylformamide, dimethylformamide / acetone or glacial acetic acid if necessary with the addition of an acid like hydrochloric acid or glacial acetic acid at temperatures between 0 and 50 ° C, but preferably at room temperature, and at a hydrogen pressure of 1 to 7 bar, but preferably from 3 to 5 bar.

The cleavage of a methoxybenzyl group can also in the presence of an oxidizing agent such as cerium (IV) ammonium nitrate in a solvent such as methylene chloride, acetonitrile or acetonitrile / water at temperatures between 0 and 50 ° C, but preferably at room temperature.

The cleavage of a 2,4-dimethoxybenzyl radical however, it is preferably carried out in trifluoroacetic acid in the presence of anisole.

The cleavage of a tert-butyl or tert-butyloxycarbonyl radical is preferably carried out by treatment with an acid such as trifluoroacetic acid or hydrochloric acid optionally using a solvent such as methylene chloride, Dioxane, ethyl acetate or ether.

The cleavage of a phthalyl radical is preferably carried out 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 dioxane Temperatures between 20 and 50 ° C.

Chiral compounds obtained can also be obtained of the general formula I in its enantiomers and / or diastereomers be separated.

For example, the Compounds of general formula I obtained, which in racemates occur, according to methods known per se (see Allinger N. L. and Eliel E. L. in "Topics in stereochemistry ", Vol. 6, Wiley Interscience, 1971) in their optical antipodes and Compounds of general formula I with at least two asymmetric Carbon atoms per se due to their physico-chemical differences known methods, e.g. by chromatography and / or fractionated Crystallization, separate into their diastereomers, which, if they accrued in racemic form, then as mentioned above in the Enantiomers can be separated.

The enantiomers are separated preferably by column separation on chiral phases or by recrystallization from an optical active solvent or by reaction with a, with the racemic compound salts or derivatives such as Esters or amides forming optically active Substance, especially acids and their activated derivatives or alcohols, and separating the mixture of diastereomeric salts or derivatives obtained in this way, e.g. due to different solubilities, whereby from the pure diastereomeric salts or derivatives the free antipodes can be released by the action of suitable agents. Especially common, optically active acids are e.g. the D and L-forms of tartaric acid, dibenzoyltartaric, Di-o-tolyltartaric, Malic acid, Mandelic, camphor sulfonic acid, glutamic acid, N-acetylglutamic, aspartic acid, N-acetyl-aspartic acid or quinic acid. The optically active alcohol is, for example, (+) - or (-) - menthol and as an optically active acyl radical in amides, for example the (+) - or (-) - Menthyioxycarbonylrest into consideration.

Furthermore, the compounds obtained of the formula I in their salts, in particular for pharmaceutical use in their physiologically tolerable Salts with inorganic or organic acids. Come as acids therefor for example hydrochloric acid, Hydrobromic acid, sulfuric acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid, maleic acid, methanesulfonic acid or ethanesulfonic into consideration.

In addition, the so obtained new compounds of formula I, if this is a carboxy group included, if desired subsequently in their salts with inorganic or organic bases, in particular for the pharmaceutical application in their physiologically acceptable Salts, transfer. As bases come here, for example, sodium hydroxide, potassium hydroxide, cyclohexylamine, Ethanolamine, diethanolamine and triethanolamine.

Some of the compounds of the general formulas II to IX used as starting products are known from the literature or can be obtained by processes known from the literature or can be obtained by the processes described above and in the examples. For example, the compounds of the general formula VIII are obtainable from the compounds of the general formula I in which R _{4 represents} a phenyl group substituted by a hydroxy-C _1-3 alkyl group, for example by reaction with alkyl or arylsulfonyl chlorides.

As already mentioned at the beginning, the new compounds of the general formula I in which R _{1 represents} a hydrogen atom or a prodrug residue have valuable pharmacological properties, in particular an inhibitory effect on various kinases, especially on receptor tyrosine kinases such as VEGFR1, VEGFR2, VEGFR3 , PDGFRα, PDGFRβ, 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, B1, B2, C, D1, D2, D3, E, F. G1, G2, H, I and K) and on viral cyclin, on the proliferation of cultured human cells, especially those of endothelial cells, for example in angiogenesis, but also on the proliferation of other cells, especially tumor cells.

The biological properties of the new compounds were tested according to the following standard procedure as follows:
Human umbilical cord endothelial cells (HUVEC) were in IMDM (Gibco BRL) supplemented with 10% fetal bovine serum (FBS) (Sigma), 50 μM β-mercaptoeethanol (Fluuka), standard antibiotics, 15 μg / ml endothelial cell growth factor (ECGS, Collaborative Biomedical Products) and 100 μg / ml heparin (Sigma) on gelatin-coated culture bottles (0.2% gelatin, Sigma) at 37 ° C., 5% CO ₂ in a water-saturated atmosphere.

To investigate the inhibitory activity of the compounds according to the invention, the cells were "starved" for 16 hours, ie kept in culture medium without growth factors (ECGS + heparin). The cells were detached from the culture bottles using trypsin / EDTA and washed once in serum-containing medium. Then 2.5 × 10 ³ cells were sown per well.

The proliferation of the cells was stimulated with 5 ng / mul VEGuF ₁₆₅ (vascular endothelial growuth factor; H. Weich, GBF Braunschweig) and 10 μg / ml heparin. As a control value, 6 wells were not stimulated per plate.

The compounds of the invention were in 100% dimethyl sulfoxide dissolved and in different dilutions added to the cultures as triplicate determinations, the maximum dimethyl sulfoxide concentration Was 0.3%.

The cells were incubated at 37 ° C. for 76 hours, then ³ H-thymidine (0.1 μCi / well, Amersham) was added for a further 16 hours in order to determine the DNA synthesis. The radioactively labeled cells were then immobilized on filter mats and the radioactivity incorporated was determined in a β-counter. 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 drug concentration, which inhibits cell proliferation by 50% (IC ₅₀ ), was derived.

• (a) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (b) 3-(Z)-{1-(4-[N-Methyl-N-(4-methylpiperazin-1-yl-methylcarbonyl)-amino]-phenylamino)-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• s(c) 3-(Z)-{1-[4-(N-Ethyl-N-methyl-aminomethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (d) 3-(Z)-{1-[4-(N-Methyl-N-{2-(dimethylamino)-ethyl-carbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (e) 3-(Z)-{1-[4-(1,2,4-Triazol-1-yl-methyl)-phenylamino]-1-(1-methyl-benzimidazol-5-yl)-methylen}-6-fluor-2-indolinon
• (f) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(1-methyl-benzimidazol-5-yl)-methylen}-6-chlor-2-indolinon
• (g) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (h) 3-(Z)-{1-(4-[N-Methansulfonyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (i) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (j) 3-(Z)-{1-(4-[N-Methyl-N-(4-methylpiperazin-1-yl-methylcarbonyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (k) 3-(Z)-{1-(4-[N-Acetyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (l) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (m) 3-(Z)-{1-(4-[N-Acetyl-N-(3-dimethylaminopropyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (n) 3-(Z)-{1-(4-[N-Propionyl-N-(3-dimethylaminopropyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (o) 3-(Z)-{1-(4-[N-Propionyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (p) 3-(Z)-{1-(4-[N-Acetyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (q) 3-(Z)-{1-(4-[4-Methylpiperazin-1-yl-methyl]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (r) 3-(Z)-{1-(4-[N-Methansulfonyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (s) 3-(Z)-{1-(4-[Pyrrolidin-1--methyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (t) 3-(Z)-{1-(4-[N-Methyl-N-(dimethylaminomethylcarbonyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (u) 3-(Z)-{1-(4-[Ethylamino-methyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (v) 3-(Z)-{1-(4-[4-Methylpiperazin-l-yl-methyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (w) 3-(Z)-{1-(4-[Dimethylamino-methyl]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (x) 3-(Z)-{1-(4-[Diethylamino-methyl]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (y) 3-(Z)-{1-[4-(Dimethylaminocarbonyl)-phenylamino]-1-(1-methyl-benzimidazol-5-yl)-methylen}-6-fluor-2-indolinon
• (z) 3-(Z)-{1-(4-[N-Propionyl-N-(3-dimethylaminopropyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (aa) 3-(Z)-{1-(4-[N-Propionyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (ab) 3-(Z)-{1-(4-[N-Methansulfonyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (ac) 3-(Z)-{1-(4-[N-Acetyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (ad) 3-(Z)-{1-(4-[N-Methyl-N-(2-dimethylaminoethyl)aminocarbonyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (ae) 3-(Z)-{1-(4-[N-Methyl-N-(3-dimethylaminopropyl)aminocarbonyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (af) 3-(Z)-{1-(4-[N-Methyl-N-(2-dimethylaminoethyl)aminocarbonyl]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (ag) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(benzimidazol-5-yl)-methylen}-2-indolinon
• (ah) 3-(Z)-{1-(4-[1-Methyl-piperazin-4-yl-methyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-dimethylaminocarbonyl-2-indolinon
• (ai) 3-(Z)-{1-[4-(Pyrrolidin-1-yl-methyl)-phenylamino]-1-(benzimidazol-5-yl)-methylen}-6-chlor-2-indolinon
• (aj) 3-(Z)-{1-(4-[N-Methyl-N-(dimethylaminomethylcarbonyl)-amino]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-2-indolinon
• (ak) 3-(Z)-{1-(4-[N-Methyl-N-(dimethylaminomethylcarbonyl)-amino]-phenylamino)-1-(1-methyl-benzimidazol-5-yl)-methylen}-6-chlor-2-indolinon
• (al) 3-(Z)-{1-(4-[N-Acetyl-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-(difluormethylendioxy)phenyl)-methylen}-6-chlor-2-indolinon
• (am) 3-(Z)-{1-(4-[N-Methyl-N-(1-methyl-4-piperidinyl)-aminocarbonyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (an) 3-(Z)-{1-(4-[N-Methyl-N-(dimethylaminomethylcarbonyl)-amino]-phenylamino)-1-(3-furyl)-methylen}-2-indolinon
• (ao) 3-(Z)-{1-(4-[N-(3-Pyridylcarbonyl)-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (ap) 3-(Z)-{1-(4-[2-(Diethylamino)ethyl-sulfonyl]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (aq) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(1-methyl-benzimidazol-5-yl)-methylen}-2-indolinon
• (ar) 3-(Z)-{1-(4-[1-Methylimidazol-2-yl]-phenylamino)-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (as) 3-(Z)-{1-[4-(Pyrrolid-2-on-1-yl)-phenylamino]-1-(1-methyl-benzimidazol-5-yl)-methylen}-6-fluor-2-indolinon
• (at) 3-(Z)-{1-[4-(3,5-Dimethyl-pyrazol-1-yl)-phenylamino]-1-(1-methyl-benzimidazol-5-yl)-methylen}-6-fluor-2-indolinon
• (au) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminosulfonyl)-phenylamino]-1-(1-methyl-benzimidazol-5-yl)-methylen}-6-fluor-2-indolinon
• (av) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(1-methyl-benzotriazol-5-yl)-methylen}-2-indolinon
• (aw) 3-(Z)-{1-(4-[(1-Methyl-piperazin-4-yl)-carbonylmethyl]-phenylamino)-1-(3,4-ethylendioxyphenyl)-methylen}-6-fluor-2-indolinon
• (ax) 3-(Z)-{1-(4-[N-(Propansulfonyl)-N-(2-dimethylaminoethyl)-amino]-phenylamino)-1-(4-pyridyl)-methylen}-6-chlor-2-indolinon
• (ay) 3-(Z)-{1-[4-(Pyrrolidin-1-yl-methyl)-phenylamino]-1-(2-methyl-benzimidazol-5-yl)-methylen}-6-chlor-2-indolinon
• (az) 3-(Z)-{1-(4-[N-Methyl-N-(4-methylpiperazin-1-yl-methylcarbonyl)-amino]-phenylamino)-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon

The test results of the following compounds (a) to (ay) of the general formula I are given by way of example:

• (a) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-chloro-2-indolinone
• (b) 3- (Z) - {1- (4- [N-Methyl-N- (4-methylpiperazin-1-yl-methylcarbonyl) amino] phenylamino) -1- (quinoxalin-6-yl) - methylene} -6-chloro-2-indolinone
• s (c) 3- (Z) - {1- [4- (N-ethyl-N-methylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-chloro-2- indolinone
• (d) 3- (Z) - {1- [4- (N-Methyl-N- {2- (dimethylamino) ethylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) - methylene} -6-fluoro-2-indolinone
• (e) 3- (Z) - {1- [4- (1,2,4-Triazol-1-yl-methyl) -phenylamino] -1- (1-methyl-benzimidazol-5-yl) -methylene} -6-fluoro-2-indolinone
• (f) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (1-methyl-benzimidazol-5-yl) -methylene} -6-chloro-2-indolinone
• (g) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-chloro-2-indolinone
• (h) 3- (Z) - {1- (4- [N-methanesulfonyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-chlorine -2-indolinone
• (i) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (j) 3- (Z) - {1- (4- [N-Methyl-N- (4-methylpiperazin-1-yl-methylcarbonyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) - methylene} -6-methoxycarbonyl-2-indolinone
• (k) 3- (Z) - {1- (4- [N-Acetyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluoro -2-indolinone
• (l) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluoro-2-indolinone
• (m) 3- (Z) - {1- (4- [N-Acetyl-N- (3-dimethylaminopropyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-chloro -2-indolinone
• (n) 3- (Z) - {1- (4- [N-Propionyl-N- (3-dimethylaminopropyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-chlorine -2-indolinone
• (o) 3- (Z) - {1- (4- [N-Propionyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphe nyl) methylene} -6-chloro-2-indolinone
• (p) 3- (Z) - {1- (4- [N-Acetyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-chloro -2-indolinone
• (q) 3- (Z) - {1- (4- [4-Methylpiperazin-1-ylmethyl] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -6-chloro-2-indolinone
• (r) 3- (Z) - {1- (4- [N-methanesulfonyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl -2-indolinone
• (s) 3- (Z) - {1- (4- [pyrrolidin-1-methyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (t) 3- (Z) - {1- (4- [N-Methyl-N- (dimethylaminomethylcarbonyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2 -indolinon
• (u) 3- (Z) - {1- (4- [ethylamino-methyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (v) 3- (Z) - {1- (4- [4-Methylpiperazin-l-ylmethyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (w) 3- (Z) - {1- (4- [Dimethylamino-methyl] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (x) 3- (Z) - {1- (4- [Diethylamino-methyl] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (y) 3- (Z) - {1- [4- (Dimethylaminocarbonyl) phenylamino] -1- (1-methyl-benzimidazol-5-yl) -methylene} -6-fluoro-2-indolinone
• (z) 3- (Z) - {1- (4- [N-Propionyl-N- (3-dimethylaminopropyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluorine -2-indolinone
• (aa) 3- (Z) - {1- (4- [N-Propionyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluoro -2-indolinone
• (ab) 3- (Z) - {1- (4- [N-methanesulfonyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluorine -2-indolinone
• (ac) 3- (Z) - {1- (4- [N-acetyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl -2-indolinone
• (ad) 3- (Z) - {1- (4- [N-methyl-N- (2-dimethylaminoethyl) aminocarbonyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl- 2-indolinone
• (ae) 3- (Z) - {1- (4- [N-Methyl-N- (3-dimethylaminopropyl) aminocarbonyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl- 2-indolinone
• (af) 3- (Z) - {1- (4- [N-Methyl-N- (2-dimethylaminoethyl) aminocarbonyl] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -6-methoxycarbonyl- 2-indolinone
• (ag) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (benzimidazol-5-yl) methylene} -2-indolinone
• (ah) 3- (Z) - {1- (4- [1-Methylpiperazin-4-ylmethyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-dimethylaminocarbonyl-2 -indolinon
• (ai) 3- (Z) - {1- [4- (Pyrrolidin-1-ylmethyl) phenylamino] -1- (benzimidazol-5-yl) methylene} -6-chloro-2-indolinone
• (aj) 3- (Z) - {1- (4- [N-Methyl-N- (dimethylaminomethylcarbonyl) amino] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -2-indolinone
• (ak) 3- (Z) - {1- (4- [N-Methyl-N- (dimethylaminomethylcarbonyl) amino] phenylamino) -1- (1-methyl-benzimidazol-5-yl) -methylene} -6 chloro-2-indolinone
• (al) 3- (Z) - {1- (4- [N-acetyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4- (difluoromethylenedioxy) phenyl) methylene} - 6-chloro-2-indolinone
• (am) 3- (Z) - {1- (4- [N-Methyl-N- (1-methyl-4-piperidinyl) aminocarbonyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluoro-2-indolinone
• (an) 3- (Z) - {1- (4- [N-Methyl-N- (dimethylaminomethylcarbonyl) amino] phenylamino) -1- (3-furyl) methylene} -2-indolinone
• (ao) 3- (Z) - {1- (4- [N- (3-pyridylcarbonyl) -N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -6-chloro-2-indolinone
• (ap) 3- (Z) - {1- (4- [2- (diethylamino) ethylsulfonyl] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -6-chloro-2-indolinone
• (aq) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (1-methyl-benzimidazol-5-yl) -methylene} -2-indolinone
• (ar) 3- (Z) - {1- (4- [1-methylimidazol-2-yl] phenylamino) -1- (quinoxalin-6-yl) methylene} -6-chloro-2-indolinone
• (as) 3- (Z) - {1- [4- (pyrrolid-2-one-1-yl) phenylamino] -1- (1-methyl-benzimidazol-5-yl) -methylene} -6-fluoro -2-indolinone
• (at) 3- (Z) - {1- [4- (3,5-Dimethyl-pyrazol-1-yl) phenylamino] -1- (1-methyl-benzimidazol-5-yl) -methylene} -6 fluoro-2-indolinone
• (au) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylamino-ethyl} aminosulfonyl) phenylamino] -1- (1-methyl-benzimidazol-5-yl) - methylene} -6-fluoro-2-indolinone
• (av) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (1-methyl-benzotriazol-5-yl) -methylene} -2-indolinone
• (aw) 3- (Z) - {1- (4 - [(1-methylpiperazin-4-yl) carbonylmethyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluoro -2-indolinone
• (ax) 3- (Z) - {1- (4- [N- (propanesulfonyl) -N- (2-dimethylaminoethyl) amino] phenylamino) -1- (4-pyridyl) methylene} -6-chloro -2-indolinone
• (ay) 3- (Z) - {1- [4- (Pyrrolidin-1-yl-methyl) -phenylamino] -1- (2-methyl-benzimidazol-5-yl) -methylene} -6-chloro-2 -indolinon
• (az) 3- (Z) - {1- (4- [N-Methyl-N- (4-methylpiperazin-1-yl-methylcarbonyl) amino] phenylamino) -1- (3,4-methylenedioxyphenyl) - methylene} -6-chloro-2-indolinone

The following table contains the results found:

Because of their inhibitory effect on the Proliferation of cells, particularly endothelial cells and Tumor cells, the compounds of the general formula are suitable I treat diseases in which the proliferation of Cells, especially that of endothelial cells, play a role.

For example, the proliferation of endothelial cells and the associated neovascularization represent a crucial step in tumor 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 hemangiomas, metastasis, rheumatoid arthritis, psoriasis and ocular neovascularization (Folkman J., Nature Med. 1, 27-31, (1995)). The therapeutic groove Endothelial cell proliferation inhibitors have been described in animal models, for example by O'Reilly et al. and Parangi et al. (O'Reilly MS et al., Cell 88, 277-285, (1997); Parangi S. et al., Proc Natl Acad Sci USA 93, 2002-2007, (1996)).

The connections of the general Formula I, their tautomers, their stereoisomers or their physiological acceptable Salts are therefore suitable, for example, for the treatment of tumors (e.g. squamous cell carcinoma, astrocytoma, Kaposi's sarcoma, glioblastoma, Lung cancer, bladder cancer, neck and neck cancer, melanoma, ovarian cancer, Prostate cancer, breast cancer, small cell lung cancer, glioma, Colorectal cancer, urogenital cancer and gastrointestinal cancer as well as hematological Cancers such as multiple myeloma), psoriasis, arthritis (e.g. Rheumatoid arthritis), hemangioma, Angiofibroma, eye diseases (e.g. diabetic retinopathy), neovascular glaucoma, kidney diseases (e.g. glomerulonephritis), diabetic nephropathy, malignant nephrosclerosis, thrombic microangiopathic Syndromes, transplant rejection and glomerulopathy, fibrotic Diseases (e.g. cirrhosis of the liver), mesangial cell proliferative diseases, Atherosclerosis, nerve tissue injuries and inhibition the reocclusion of vessels after balloon catheter treatment, with vascular prosthetics or after the insertion of mechanical devices for keeping vessels open (e.g. Stents), or other diseases in which cell proliferation or angiogenesis play a role.

Because of their biological properties can the compounds of the invention alone or in combination with other pharmacologically active Compounds are used, for example in tumor therapy in monotherapy or in combination with other anti-tumor therapeutic agents, for example in combination with topoisomerase inhibitors (e.g. Etoposides), mitotic inhibitors (e.g. vinblastine, taxol), interacting with nucleic acids Compounds (e.g. cis-platinum, Cyclophosphamide, adriamycin), hormone antagonists (e.g. tamoxifen), Inhibitors of metabolic processes (e.g. 5-FU etc.), cytokines (e.g. Interferons), receptor tyrosine kinase and kinase inhibitors, antibodies or in combination with radiation therapy etc. These combinations can can be administered either simultaneously or sequentially.

In pharmaceutical application become the compounds of the invention usually in warm-blooded Vertebrates, especially in humans, in doses of 0.01-100 mg / kg Body weight, preferably at 0.1-20 mg / kg used. For administration, these are used with one or more common inert carriers and / or diluents, e.g. with cornstarch, Milk sugar, cane sugar, microcrystalline cellulose, magnesium stearate, Polyvinyl pyrrolidone, citric acid, Tartaric acid, Water, water / ethanol, Water / glycerin, water / sorbitol, water / polyethylene glycol, propylene glycol, Stearyl alcohol, carboxymethyl cellulose or fatty substances such as hard fat or their suitable mixtures in conventional pharmaceutical preparations such as tablets, coated tablets, capsules, powders, injection solutions, Ampoules, suspensions, solutions, Sprays or suppositories incorporated.

The following examples are intended to explain the invention in more detail:
Used abbreviations:
DMF = N, N-dimethylformamide
DMSO = dimethyl sulfoxide
HOBT = 1-hydroxy-1H-benzotriazole
TBTU = O-benzotriazol-1-yl-N, N, N ', N'-tetramethyluronium tetrafluoroborate
THF = tetrahydrofuran

Preparation of the starting compounds:

Example 1:

5-Carboxy-2-methyl-isoindole-1,3-dione

19.2 g of trimellitic anhydride are stirred in 100 ml of N-methylformamide for 4 hours at 140 ° C. and then at room temperature overnight. After adding 300 ml of water, the mixture is stirred for a further 12 hours; then the precipitate is filtered off, washed with water and dried at 80 ° C.
Yield: 15.5 g (75% of theory)
R _f value: 0.59 (RP-8, methanol / 5% sodium chloride solution = 7: 3) C ₁₀ H ₇ NO ₄ Mass spectrum: m / z = 204 [MH] ^-

Example II:

3,4-Ethylendioxybenzoesäure

A suspension of 80.1 g calcium hypochlorite in 360 ml water and a suspension of 6.72 g sodium hydroxide and 56.4 g sodium carbonate in 170 ml water are combined and heated to 50 ° C. with stirring. The precipitate is removed by filtration and 25.0 g of 1,4-benzodioxan-6-yl-methyl ketone are added to the solution obtained. The mixture is stirred at 60 ° C. for 15 h and, after cooling to room temperature, extracted with ethyl acetate. The aqueous phase is adjusted to a pH of 3 by adding concentrated hydrochloric acid with ice cooling. The precipitated product is filtered off, washed with water and dried at 90 ° C.
Yield: 18.8 g (74% of theory)
R _f value: 0.65 (silica gel, dichloromethane / methanol / acetic acid = 90: 10: 1) C ₉ H ₈ O ₄

Example III

1-methylbenzimidazole-5-carboxylic acid

25.0 g of 4-methylamino-3-nitrobenzoic acid, dissolved in 200 ml of DMF, are hydrogenated with the addition of 2.5 g of palladium on activated carbon (10%) for 5 hours at 30 psi of hydrogen pressure. The catalyst is filtered off, the solvent is distilled off. The residue is stirred with diethyl ether, suction filtered and dried. The crude product (19.7 g) thus obtained is heated under reflux in 250 ml of formic acid for 2 hours. After the solvent has been distilled off, the residue is stirred with diethyl ether, suction filtered and dried.
Yield: 21 g (94% of theory)
R _f value: 0.25 (silica gel, dichloromethane / methanol / acetic acid = 90: 10: 1) C ₉ H ₈ N ₂ O ₂

Example IV:

2-Dibenzylaminooxazol-4-carboxylic acid

21.6 g of N-benzylurea and 28.7 g of ethyl bromopyruvate are refluxed in 120 ml of ethanol for 18 hours. The one by distilling off of the solvent preserved oily Residue comes with soda solution (10 g in 170 ml of water) and 100 ml of diethyl ether and 2 hours touched. After adding 200 ml of ethyl acetate, the phases are separated organic phase extracted twice with water and evaporated to dryness.

The intermediate (11.8 g) is dissolved in 80 ml DMSO and mixed with 5.95 g of potassium tert-butoxide. After stirring for 90 minutes 6.43 ml of benzyl bromide are slowly added dropwise at room temperature and the mixture was stirred for a further 3 hours. The mixture is poured onto 400 ml of ice water and extracted twice with ethyl acetate. The organic phases are combined, counter-extracted with water and evaporated to dryness.

For ester hydrolysis, the residue is dissolved in 200 ml of ethanol, mixed with 100 ml of 1 molar sodium hydroxide solution and stirred for 2 hours. After the ethanol has been distilled off, the mixture is extracted with diethyl ether, the aqueous phase is neutralized with 100 ml of 1 molar hydrochloric acid and extracted with ethyl acetate. The ethyl acetate phase is counter-extracted with water, dried with sodium sulfate and evaporated to dryness. The oily crude product is stirred with petroleum ether / diethyl ether, suction filtered and dried at 40 ° C.
Yield: 11.6 g (28% of theory)
R _f value: 0.4 (silica gel, dichloromethane / methanol / acetic acid 90: 10: 1) C ₁₈ H ₁₆ N ₂ O ₃ Mass spectrum: m / z = 309 [M + H] ⁺

Example V

2- (4-fluoro-2-nitrophenyl) -malonsäuredimethylesters

185 g of potassium tert-butoxide are added to a solution of 188 ml of dimethyl malonate in 970 ml of N-methylpyrrolidone while cooling with ice and the mixture is stirred for 2 hours. 150 ml of 2,5-difluoronitrobenzene are added dropwise to the resulting slurry in the course of 30 minutes, and the mixture is then stirred at 85 ° C. for 6 hours. The mixture is poured onto 4 liters of ice water and 250 ml of concentrated hydrochloric acid and extracted with 2 liters of ethyl acetate. The organic phase is dried with sodium sulfate and concentrated. The oily residue is stirred twice with water and then taken up in 600 ml of ethyl acetate. The solution is dried with sodium sulfate and evaporated to dryness. The crystallized crude product is recrystallized from 600 ml of ethyl acetate / hexane = 2: 8 and dried.
Yield: 222 g (59% of theory)
R _f value: 0.4 (silica gel, cyclohexane / ethyl acetate = 5: 1) C ₁₁ H ₁₀ FNO ₆ Mass spectrum: m / z = 270 [MH] ^-

Example VI:

4-fluoro-2-nitrophenyl acetic acid

50.0 g of dimethyl 2- (4-fluoro-2-nitrophenyl) malonate are stirred in 400 ml of 6 molar hydrochloric acid for 20 hours at 100 ° C., then mixed with 400 ml of water and cooled to 0 ° C. The resulting precipitate is filtered off, washed with water and 100 ml of petroleum ether and dried.
Yield: 34.5 g (94% of theory)
R _f value: 0.3 (silica gel, cyclohexane / ethyl acetate = 5: 2 C ₈ H ₆ FNO ₄ Mass spectrum: m / z = 244 [M + 2Na-H] ⁺

Example VII:

6-fluoro-2-indolinone

119 g of 4-fluoro-2-nitrophenylacetic acid are hydrogenated in 600 ml of acetic acid with the addition of 20 g of palladium on activated carbon (10%) under 50 psi of hydrogen pressure. The catalyst is filtered off, the solvent is distilled off. The crude product is stirred with 500 ml of petroleum ether, suction filtered, washed with water and dried.
Yield: 82.5 g (91% of theory)
R _f value: 0.31 (silica gel, petroleum ether / ethyl acetate = 1: 1) C ₈ H ₆ FNO Mass spectrum: m / z = 210 [M + CH ₃ COO] ^-

Example VIII:

1-Acetyl-6-fluoro-2-indolinone

82.5 g of 6-fluoro-2-indolinone are stirred in 180 ml of acetic anhydride at 130 ° C. for 3 hours. After cooling to room temperature, the precipitate is filtered off, washed with 100 ml of petroleum ether and dried.
Yield: 64.8 g (61% of theory)
R _f value: 0.75 (silica gel, petroleum ether / ethyl acetate = 1: 1) C ₁₀ H ₈ FNO ₂ Mass spectrum: m / z = 192 [MH] ^-

• (VIII.1) 1-Acetyl-2-indolinon aus 2-Indolinon und Essigsäureanhydrid
• (VIII.2) 1-Acetyl-6-chlor-2-indolinon aus 6-Chlor-2-indolinon und Essigsäureanhydrid
• (VIII.3) 1-Acetyl-6-methoxycarbonyl-2-indolinon aus 6-Methoxycarbonyl-2-indolinon und Essigsäureanhydrid

The following compounds are prepared analogously to Example VIII:

• (VIII.1) 1-acetyl-2-indolinone from 2-indolinone and acetic anhydride
• (VIII.2) 1-acetyl-6-chloro-2-indolinone from 6-chloro-2-indolinone and acetic anhydride
• (VIII.3) 1-acetyl-6-methoxycarbonyl-2-indolinone from 6-methoxycarbonyl-2-indolinone and acetic anhydride

Example IX

1-acetyl-3- [1-hydroxy-1- (2-furyl) methylene] -2-indolinone

An ice-cooled solution of 7.0 g of 1-acetyl-2-indolinone and 10.8 g of DMAP in 60 ml of DMF is mixed with 4.4 ml of furan-2-carboxylic acid chloride. The mixture is stirred for 1 hour at room temperature, then concentrated to 40 ml. Poured hydrochloric acid and 500 ml of ice water. The precipitate is filtered off, washed successively with ethanol and diethyl ether and dried.
Yield: 8.67 g (81% of theory)
R _f value: 0.6 (silica gel, ethyl acetate) C ₁₅ H ₁₁ NO ₄ Melting point: 128-130 ° C

• (IX.1) 1-Acetyl-6-chlor-3-[1-hydroxy-1-(2-pyrrolyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-2-indolinon und Pyrrol-2-carbonsäure

The following compound is produced analogously to Example IX:

• (IX.1) 1-acetyl-6-chloro-3- [1-hydroxy-1- (2-pyrrolyl) methylene] -2-indolinone from 1-acetyl-6-chloro-2-indolinone and pyrrol-2- carboxylic acid

Example X

1-acetyl-3- [1-hydroxy-1- (2-pyrazinyl) methylene] -2-indolinone

4.38 g of 1-acetyl-2-indolinone, 3.41 g of pyrazine-2-carboxylic acid, 8.83 g of TBTU, 4.21 g of HOBT hydrate and 21.8 ml of ethyldiisopropylamine are stirred in 70 ml of DMF for 15 hours at room temperature. The batch is concentrated to 400 ml ice water and 10 ml. Poured hydrochloric acid and stirred for 1 hour. The precipitate is filtered off, washed with water, stirred with methanol, suction filtered again, washed with methanol and dried at 100 ° C.
Yield: 4.43 g (63% of theory)
R _f value: 0.2 (silica gel, petroleum ether / dichloromethane / methanol = 5: 4: 1) C ₁₅ H ₁₁ N ₃ O ₃ Mass spectrum: m / z = 280 [MH] ^-

• (X.1) 1-Acetyl-3-[1-hydroxy-1-(3,4-methylendioxyphenyl)methylen]-2-indolinon aus 1-Acetyl-2-indolinon und 3,4-Methylendioxybenzoesäure
• (X.2) 1-Acetyl-3-[1-hydroxy-1-(3-thienyl)methylen]-2-indolinon aus 1-Acetyl-2-indolinon und Thiophen-3-carbonsäure
• (X.3) 1-Acetyl-3-[1-hydroxy-1-(5-methylisoxazol-3-yl)methylen]-2-indolinon aus 1-Acetyl-2-indolinon und 5-Methylisoxazol-3-carbonsäure
• (X.4) 1-Acetyl-3-[1-hydroxy-1-(3-methylpyrazol-5-yl)methylen]-2-indolinon aus 1-Acetyl-2-indolinon und 3-Methylpyrazol-5-carbonsäure
• (X.5) 1-Acetyl-3-[1-hydroxy-1-(4-acetylamino-3-nitrophenyl)methylen]-2-indolinon aus 1-Acetyl-2-indolinon und 4-Acetylamino-3-nitrobenzoesäure
• (X.6) 1-Acetyl-3-{1-hydroxy-1-[2-(dibenzylamino)oxazol-4-yl]methylen}-2-indolinon aus 1-Acetyl-2-indolinon und 2-(Dibenzylamino)oxazol-4-carbonsäure, wobei der nach Zugabe von Wasser und Salzsäure erhaltene Niederschlag chromatographisch an Kieselgel (Eluent: Petrolether/Dichlormethan/Ethylacetat = 5:4:1) gereinigt, anschließend mit Diethylether verrührt, abgesaugt und getrocknet wird.
• (X.7) 1-Acetyl-3-[1-hydroxy-1-(2-methyl-isoindol-1,3-dion-5-yl)methylen]-2-indolinon aus 1-Acetyl-2-indolinon und 2-Methyl-isoindol-1,3-dion-5-carbonsäure
• (X.8) 1-Acetyl-6-chlor-3-[1-hydroxy-1-(4-acetylamino-3-nitrophenyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-2-indolinon und 4-Acetylamino-3-nitrobenzoesäure
• (X.9) 1-Acetyl-6-chlor-3-[1-hydroxy-1-(4-pyridazinyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-2-indolinon und Pyridazin-4-carbonsäure
• (X.10) 1-Acetyl-6-chlor-3-[1-hydroxy-1-(3,4-methylendioxyphenyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-2-indolinon und 3,4-Methylendioxybenzoesäure
• (X.11) 1-Acetyl-6-chlor-3-[1-hydroxy-1-(3,4-ethylendioxyphenyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-2-indolinon und 3,4-Ethylendioxybenzoesäure
• (X.12) 1-Acetyl-6-chlor-3-{1-hydroxy-1-[3,4-(difluormethylen)dioxyphenyl]methylen}-2-indolinon aus 1-Acetyl-6-chlor-2-indolinon und 3,4-(Difluormethylen)dioxybenzoesäure
• (X.13) 1-Acetyl-6-fluor-3-[1-hydroxy-1-(3,4-ethylendioxyphenyl)methylen]-2-indolinon aus 1-Acetyl-6-fluor-2-indolinon und 3,4-Ethylendioxybenzoesäure
• (X.14) 1-Acetyl-3-[1-hydroxy-1-(3-furyl)methylen]-2-indolinon aus 1-Acetyl-2-indolinon und Furan-3-carbonsäure, wobei vor Zugabe des Eiswassers das Lösungsmittel abdestilliert wird.
• (X.15) 1-Acetyl-3-[1-hydroxy-1-(4-methylamino-3-nitrophenyl)methylen]-2-indolinon aus 1-Acetyl-2-indolinon und 4-Methylamino-3-nitrobenzoesäure
• (X.16) 1-Acetyl-6-fluor-3-[1-hydroxy-1-(4-methylamino-3-nitrophenyl)methylen]-2-indolinon aus 1-Acetyl-6-fluor-2-indolinon und 4-Methylamino-3-nitrobenzoesäure
• (X.17) 1-Acetyl-6-chlor-3-[1-hydroxy-1-(chinazolin-6-yl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-2-indolinon und Chinazolin-6-carbonsäure (welche durch alkalische Verseifung des Methylesters hergestellt wird).
• (X.18) 1-Acetyl-3-[1-hydroxy-1-(1-methyl-benzotriazol-5-yl)methylen]-2-indolinon aus 1-Acetyl-2-indolinon und 1-Methylbenzotriazol-5-carbonsäure (welche analog der Darstellung von 1-Methylbenzotriazol, beschrieben in: A. Reissert, Chem. Ber. 47 (1914) 676, hergestellt wird).

The following compounds are produced analogously to Example X:

• (X.1) 1-acetyl-3- [1-hydroxy-1- (3,4-methylenedioxyphenyl) methylene] -2-indolinone from 1-acetyl-2-indolinone and 3,4-methylenedioxybenzoic acid
• (X.2) 1-acetyl-3- [1-hydroxy-1- (3-thienyl) methylene] -2-indolinone from 1-acetyl-2-indolinone and thiophene-3-carboxylic acid
• (X.3) 1-acetyl-3- [1-hydroxy-1- (5-methylisoxazol-3-yl) methylene] -2-indolinone from 1-acetyl-2-indolinone and 5-methylisoxazole-3-carboxylic acid
• (X.4) 1-acetyl-3- [1-hydroxy-1- (3-methylpyrazol-5-yl) methylene] -2-indolinone from 1-acetyl-2-indolinone and 3-methylpyrazole-5-carboxylic acid
• (X.5) 1-acetyl-3- [1-hydroxy-1- (4-acetylamino-3-nitrophenyl) methylene] -2-indolinone from 1-acetyl-2-indolinone and 4-acetylamino-3-nitrobenzoic acid
• (X.6) 1-acetyl-3- {1-hydroxy-1- [2- (dibenzylamino) oxazol-4-yl] methylene} -2-indolinone from 1-acetyl-2-indolinone and 2- (dibenzylamino) oxazole-4-carboxylic acid, the precipitate obtained after adding water and hydrochloric acid being purified chromatographically on silica gel (eluent: petroleum ether / dichloromethane / ethyl acetate = 5: 4: 1), then stirred with diethyl ether, suction filtered and dried.
• (X.7) 1-acetyl-3- [1-hydroxy-1- (2-methyl-isoindol-1,3-dione-5-yl) methylene] -2-indolinone from 1-acetyl-2-indolinone and 2-methyl-isoindole-1,3-dione-5-carboxylic acid
• (X.8) 1-acetyl-6-chloro-3- [1-hydroxy-1- (4-acetylamino-3-nitrophenyl) methylene] -2-indolinone from 1-acetyl-6-chloro-2-indolinone and 4-acetylamino-3-nitrobenzoic acid
• (X.9) 1-acetyl-6-chloro-3- [1-hydroxy-1- (4-pyridazinyl) methylene] -2-indolinone from 1-acetyl-6-chloro-2-indolinone and pyridazin-4- carboxylic acid
• (X.10) 1-acetyl-6-chloro-3- [1-hydroxy-1- (3,4-methylenedioxyphenyl) methylene] -2-indolinone from 1-acetyl-6-chloro-2-indolinone and 3, 4-methylenedioxybenzoic acid
• (X.11) 1-acetyl-6-chloro-3- [1-hydroxy-1- (3,4-ethylenedioxyphenyl) methylene] -2-indolinone from 1-acetyl-6-chloro-2-indolinone and 3, 4-Ethylendioxybenzoesäure
• (X.12) 1-Acetyl-6-chloro-3- {1-hydroxy-1- [3,4- (difluoromethylene) dioxyphenyl] methylene} -2-indolinone from 1-acetyl-6-chloro-2-indolinone and 3,4- (difluoromethylene) dioxybenzoic acid
• (X.13) 1-acetyl-6-fluoro-3- [1-hydroxy-1- (3,4-ethylenedioxyphenyl) methylene] -2-indolinone from 1-acetyl-6-fluoro-2-indolinone and 3, 4-Ethylendioxybenzoesäure
• (X.14) 1-acetyl-3- [1-hydroxy-1- (3-furyl) methylene] -2-indolinone from 1-acetyl-2-indolinone and furan-3-carboxylic acid, with the Solvent is distilled off.
• (X.15) 1-acetyl-3- [1-hydroxy-1- (4-methylamino-3-nitrophenyl) methylene] -2-indolinone from 1-acetyl-2-indolinone and 4-methylamino-3-nitrobenzoic acid
• (X.16) 1-acetyl-6-fluoro-3- [1-hydroxy-1- (4-methylamino-3-nitrophenyl) methylene] -2-indolinone from 1-acetyl-6-fluoro-2-indolinone and 4-methylamino-3-nitrobenzoic acid
• (X.17) 1-acetyl-6-chloro-3- [1-hydroxy-1- (quinazolin-6-yl) methylene] -2-indolinone from 1-acetyl-6-chloro-2-indolinone and quinazoline- 6-carboxylic acid (which is produced by alkaline saponification of the methyl ester).
• (X.18) 1-acetyl-3- [1-hydroxy-1- (1-methyl-benzotriazol-5-yl) methylene] -2-indolinone from 1-acetyl-2-indolinone and 1-methylbenzotriazol-5- carboxylic acid (which is prepared analogously to the preparation of 1-methylbenzotriazole, described in: A. Reissert, Chem. Ber. 47 (1914) 676).

Example XI

1-Acetyl-6-chloro-3- [1-hydroxy-1- (4-pyridyl) methylene] -2-indolinone

6.3 g of 1-acetyl-6-chloro-2-indolinone, 4.06 g of pyridine-4-carboxylic acid, 10.6 g of TBTU and 21 ml of triethylamine are stirred in 60 ml of DMF for 15 hours at room temperature. The batch is mixed with water, then adjusted to pH 5 by adding 10% acetic acid. The precipitate is filtered off with suction, washed with water and taken up in ethyl acetate. The solution obtained is dried with sodium sulfate and evaporated almost to dryness. The precipitate obtained is filtered off and dried at 100 ° C.
Yield: 6.5 g (69% of theory)
R _f value: 0.6 (RP8, methanol / 5% NaCl = 4: 1) C _{1 6} H ₁₁ ClN ₂ O ₃ Mass spectrum: m / z = 313 [MH] ^-
Melting point: 215-217 ° C

• (XI.1) 1-Acetyl-6-chlor-3-[1-hydroxy-1-(3-pyridyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-2-indolinon und Pyridin-3-carbonsäure
• (XI.2) 1-Acetyl-6-methoxycarbonyl-3-[1-hydroxy-1-(3,4-ethylendioxyphenyl)-methylen]-2-indolinon aus 1-Acetyl-6-methoxycarbonyl-2-indolinon und 3,4-Ethylendioxybenzoesäure
• (XI.3) 1-Acetyl-3-[1-hydroxy-1-(4-imidazolyl)methylen]-2-indolinon aus 1-Acetyl-2-indolinon und Imidazol-4-carbonsäure, wobei vor der Wasserzugabe das Lösungsmittel abdestilliert wird.
• (XI.4) 1-Acetyl-6-methoxycarbonyl-3-[1-hydroxy-1-(3,4-methylendioxyphenyl)-methylen]-2-indolinon aus 1-Acetyl-6-methoxycarbonyl-2-indolinon und 3,4-Methylendioxybenzoesäure

The following compounds are produced analogously to Example XI:

• (XI.1) 1-acetyl-6-chloro-3- [1-hydroxy-1- (3-pyridyl) methylene] -2-indolinone from 1-acetyl-6-chloro-2-indolinone and pyridine-3- carboxylic acid
• (XI.2) 1-acetyl-6-methoxycarbonyl-3- [1-hydroxy-1- (3,4-ethylenedioxyphenyl) methylene] -2-indolinone from 1-acetyl-6-methoxycarbonyl-2-indolinone and 3 , 4-Ethylendioxybenzoesäure
• (XI.3) 1-acetyl-3- [1-hydroxy-1- (4-imidazolyl) methylene] -2-indolinone from 1-acetyl-2-indolinone and imidazole-4-carboxylic acid, the solvent being added before the water is distilled off.
• (XI.4) 1-acetyl-6-methoxycarbonyl-3- [1-hydroxy-1- (3,4-methylenedioxyphenyl) methylene] -2-indolinone from 1-acetyl-6-methoxycarbonyl-2-indolinone and 3 , 4-methylenedioxybenzoic acid

Example XII

1-Acetyl-6-chloro-3- [1-hydroxy-1- (1-methyl-5-benzimidazolyl) methylene] -2-indolinone

3.5 g of 1-acetyl-6-chloro-2-indolinone, 3.4 g of 1-methylbenzimidazole-5-carboxylic acid, 6.1 g of TBTU, 2.9 g of HOBT hydrate and 8.7 ml of ethyldiisopropylamine are stirred in 100 ml of DMF for 15 hours at room temperature. The mixture is mixed with water and extracted with ethyl acetate, the crude product partially precipitating. The residue obtained by distilling off the solvent is taken up in dichloromethane and a little methanol and extracted with water. The organic phase is concentrated, the residue is stirred in succession with ethyl acetate and diethyl ether, suction filtered and dried.
Yield: 2.2 g (35% of theory)
R _f value: 0.17 (silica gel, ethyl acetate / methanol / ammonia solution = 80: 20: 1) C ₁₉ H ₁₄ ClN ₃ O ₃ Mass spectrum: m / z = 368/390 [M + H] ⁺

• (XII.1) 1-Acetyl-6-chlor-3-[1-hydroxy-1-(1-benzyl-5-imidazolyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-2-indolinon und 1-Benzylimidazol-5-carbonsäure, wobei das flüssig anfallende Produkt durch Einengen der Ethylacetatphase erhalten wird.

The following connection is established analogously to Example XII:

• (XII.1) 1-acetyl-6-chloro-3- [1-hydroxy-1- (1-benzyl-5-imidazolyl) methylene] -2-indolinone from 1-acetyl-6-chloro-2-indolinone and 1-Benzylimidazole-5-carboxylic acid, the liquid product being obtained by concentrating the ethyl acetate phase.

Example XIII

1-acetyl-3- [1-chloro-1- (4-acetylamino-3-nitrophenyl) methylene] -2-indolinone

A suspension of 11.4 g of 1-acetyl-3- (1-hydroxy-1- (4-acetylamino-3-nitrophenyl) methylene) -2-indolinone and 9.37 g of phosphorus pentachloride in 200 ml of dioxane is stirred at 100 ° C. for 4 hours , After adding a further 2.0 g of phosphorus pentachloride, the mixture is stirred at 100 ° C. for a further 3 hours. The solvent is then distilled off, the residue is stirred with 100 ml of ethyl acetate, suction filtered, washed with ethyl acetate and dried at 60.degree.
Yield: 6.40 g (53% of theory)
R _f value: 0.7 (silica gel, dichloromethane / ethyl acetate = 9: 1) C ₁₉ H ₁₄ CIN ₃ O ₅ Mass spectrum: m / z = 398/400 [MH] ^-

• (XIII.1) 1-Acetyl-6-chlor-3-[1-chlor-1-(4-acetylamino-3-nitrophenyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-3-[1-hydroxy-1-(4-acetylamino-3-nitrophenyl)methylen]-2-indolinon
• (XIII.2) 1-Acetyl-6-chlor-3-[1-chlor-1-(3-pyridyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-3-[1-hydroxy-1-(3-pyridyl)methylen]-2-indolinon
• (XIII.3) 1-Acetyl-6-chlor-3-[1-chlor-1-(4-pyridyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-3-[1-hydroxy-1-(4-pyridyl)methylen]-2-indolinon
• (XIII.4) 6-Chlor-3-[1-chlor-1-(1-methyl-5-benzimidazolyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-3-[1-hydroxy-1-(1-methyl-5-benzimidazolyl)methylen]-2-indolinon
• (XIII.5) 1-Acetyl-6-chlor-3-[1-chlor-1-(1-benzyl-5-imidazolyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-3-[1-hydroxy-1-(1-benzyl-5-imidazolyl)methylen]-2-indolinon

The following compounds are prepared analogously to Example XIII:

• (XIII.1) 1-Acetyl-6-chloro-3- [1-chloro-1- (4-acetylamino-3-nitrophenyl) methylene] -2-indolinone from 1-acetyl-6-chloro-3- [1 -hydroxy-1- (4-acetylamino-3-nitrophenyl) methylene] -2-indolinone
• (XIII.2) 1-Acetyl-6-chloro-3- [1-chloro-1- (3-pyridyl) methylene] -2-indolinone from 1-acetyl-6-chloro-3- [1-hydroxy-1 - (3-pyridyl) methylene] -2-indolinone
• (XIII.3) 1-Acetyl-6-chloro-3- [1-chloro-1- (4-pyridyl) methylene] -2-indolinone from 1-acetyl-6-chloro-3- [1-hydroxy-1 - (4-pyridyl) methylene] -2-indolinone
• (XIII.4) 6-chloro-3- [1-chloro-1- (1-methyl-5-benzimidazolyl) methylene] -2-indolinone from 1-acetyl-6-chloro-3- [1-hydroxy-1 - (1-methyl-5-benzimidazolyl) methylene] -2-indolinone
• (XIII.5) 1-Acetyl-6-chloro-3- [1-chloro-1- (1-benzyl-5-imidazolyl) methylene] -2-indolinone from 1-acetyl-6-chloro-3- [1 -hydroxy-1- (1-benzyl-5-imidazolyl) methylene] -2-indolinone

Example XIV

1-Acetyl-6-chloro-3- [1-chloro-1- (2-pyrrolyl) methylene] -2-indolinone

A suspension of 4.5 g of 1-acetyl-6-chloro-3- [1-hydroxy-1- (2-pyrrolyl) methylene] -2-indolinone and 3.4 g of phosphorus pentachloride in 50 ml of dioxane and 50 ml of toluene is 3 hours at 90 ° C stirred. The solvent is then distilled off and the residue is purified by chromatography on silica gel (eluent: toluene). Yield: 2.2 g (46% of theory) R _f value: 0.8 (silica gel, toluene) C ₁₅ H ₁₀ Cl ₂ N ₂ O ₂

• (XIV.1) 1-Acetyl-6-chlor-3-[1-chlor-1-(4-pyridazinyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-3-(1-hydroxy-1-(4-pyridazinyl)methylen)-2-indolinon, wobei als Fliessmittelsystem Dichlormethan/Methanol = 9:1 verwendet wird.

The following connection is established analogously to Example XIV:

• (XIV.1) 1-acetyl-6-chloro-3- [1-chloro-1- (4-pyridazinyl) methylene] -2-indolinone from 1-acetyl-6-chloro-3- (1-hydroxy-1 - (4-pyridazinyl) methylene) -2-indolinone, dichloromethane / methanol = 9: 1 being used as the superplasticizer system.

Example XV

1-acetyl-3- [1-chloro-1- (5-methyl-3-isoxazolyl) methylene] -2-indolinone

3.00 g of 1-acetyl-3- [1-hydroxy-1- (5-methyl-3-isoxazolyl) methylene] -2-indolinone, 5.09 ml of carbon tetrachloride and 5.54 g of triphenylphosphine are heated under reflux in 100 ml of THF for 8 hours. The residue obtained after distilling off the solvent is purified by chromatography on silica gel (eluent: petroleum ether / ethyl acetate = 9: 1).
Yield: 2.53 g (79% of theory)
R _f value: 0.7 (silica gel, petroleum ether / dichloromethane / methanol = 5: 4: 1) C ₁₅ H ₁₁ ClN ₂ O ₃ Mass spectrum: m / z = 302/304 [M] ⁺

• (XV.1) 1-Acetyl-3-[1-chlor-1-(3-methyl-5-pyrazolyl)methylen]-2-indolinon aus 1-Acetyl-3-[1-hydroxy-1-(3-methyl-5-pyrazolyl)methylen]-2-indolinon

The following connection is established analogously to Example XV:

• (XV.1) 1-acetyl-3- [1-chloro-1- (3-methyl-5-pyrazolyl) methylene] -2-indolinone from 1-acetyl-3- [1-hydroxy-1- (3- methyl-5-pyrazolyl) methylene] -2-indolinone

Example XVI

1-Acetyl-6-chloro-3- [1-methoxy-1- (3,4-methylenedioxyphenyl) methylene] -2-indolinone

A solution of 20.9 g of 1-acetyl-6-chloro-3- [1-hydroxy-1- (3,4-methylenedioxyphenyl) methylene] -2-indolinone and 40 ml of ethyldiisopropylamine in 200 ml of dichloromethane is added in portions with 17.3 g of trimethyloxonium tetrafluoroborate , stirred overnight and then extracted twice with water. The organic phase is dried with magnesium sulfate and evaporated to dryness. The residue is stirred with methanol, suction filtered, washed with methanol and dried at 80 ° C.
Yield: 9.40 g (43% of theory)
R _f value: 0.7 (silica gel, petroleum ether / dichloromethane / methanol = 5: 4: 1) C ₁₉ H ₁₄ ClNO ₅ Mass spectrum: m / z = 371/373 [M] ⁺

• (XVI.1) 1-Acetyl-6-chlor-3-[1-methoxy-1-(3,4-ethylendioxyphenyl)methylen]-2-indolinon aus 1-Acetyl-6-chlor-3-[1-hydroxy-1-(3,4-ethylendioxyphenyl)methylen]-2-indolinon
• (XVI.2) 1-Acetyl-6-chlor-3-{1-methoxy-1-[3,4-(difluormethylendioxy)phenyl]methylen}-2-indolinon aus 1-Acetyl-6-chlor-3-{1-hydroxy-1-[3,4-(difluormethylendioxy)phenyl]methylen}-2-indolinon
• (XVI.3) 1-Acetyl-3-[1-methoxy-1-(2-methyhl-isoindol-1,3-dion-5-yl)methylen]-2-indolinon aus 1-Acetyl-3-[1-hydroxy-1-(2-methyl-isoindol-1,3-dion-5-yl)methylen]-2-indolinon
• (XVI.4) 1-Acetyl-3-[1-methoxy-1-(3-furyl)methylen]-2-indolinon aus 1-Acetyl-3-[1-hydroxy-1-(3-furyl)methylen]-2-indolinon
• (XVI.5) 1-Acetyl-3-[1-methoxy-1-(2-dibenzylamino-4-oxazolyl)methylen]-2-indolinon aus 1-Acetyl-3-[1-hydroxy-1-(2-dibenzylamino-4-oxazolyl)methylen]-2-indolinon
• (XVI.6) 1-Acetyl-6-methoxycarbonyl-3-[1-methoxy-1-(3,4-ethylendioxyphenyl)-methylen]-2-indolinon aus 1-Acetyl-6-methoxycarbonyl-3-[1-hydroxy-1-(3,4-ethylendioxyphenyl)methylen]-2-indolinon
• (XVI.7) 1-Acetyl-6-fluor-3-[1-methoxy-1-(3,4-ethylendioxyphenyl)methylen]-2-indolinon aus 1-Acetyl-6-fluor-3-[1-hydroxy-1-(3,4-ethylendioxyphenyl)methylen]-2-indolinon
• (XVI.8) 1-Acetyl-3-[1-methoxy-1-(4-methylamino-3-nitrophenyl)methylen]-2-indolinon aus 1-Acetyl-3-[1-hydroxy-1-(4-methylamino-3-nitrophenyl)methylen]-2-indolinon
• (XVI.9) 1-Acetyl-6-fluor-3-[1-methoxy-1-(4-methylamino-3-nitrophenyl)methylen]-2-indolinon aus 1-Acetyl-6-fluor-3-[1-hydroxy-1-(4-methylamino-3-nitrophenyl)methylen]-2-indolinon
• (XVI.10) 1-Acetyl-6-chlor-3-[1-methoxy-l-(chinazolin-6-yl)-methylen]-2-indolinon aus 1-Acetyl-6-chlor-3-[1-hydroxy-l-(chinazolin-6-yl)methylen]-2-indolinon
• (XVI.11) 1-Acetyl-6-methoxycarbonyl-3-[1-methoxy-1-(3,4-methylendioxyphenyl)-methylen]-2-indolinon aus 1-Acetyl-6-methoxycarbonyl-3-[1-hydroxy-1-(3,4-methylendioxyphenyl)-methylen]-2-indolinon
• (XVI.12) 1-Acetyl-3-[1-methoxy-1-(1-methylbenzotriazol-5-yl)methylen]-2-indolinon aus 1-Acetyl-3-[1-hydroxy-1-(1-methylbenzotriazol-5-yl)methylen]-2-indolinon

The following compounds are prepared analogously to Example XVI:

• (XVI.1) 1-acetyl-6-chloro-3- [1-methoxy-1- (3,4-ethylenedioxyphenyl) methylene] -2-indolinone from 1-acetyl-6-chloro-3- [1-hydroxy -1- (3,4-ethylenedioxyphenyl) methylene] -2-indolinone
• (XVI.2) 1-acetyl-6-chloro-3- {1-methoxy-1- [3,4- (difluoromethylenedioxy) phenyl] methylene} -2-indolinone from 1-acetyl-6-chloro-3- { 1-hydroxy-1- [3,4- (difluoromethylenedioxy) phenyl] methylene} -2-indolinone
• (XVI.3) 1-acetyl-3- [1-methoxy-1- (2-methyl-isoindole-1,3-dione-5-yl) methylene] -2-indolinone from 1-acetyl-3- [1 -hydroxy-1- (2-methyl-isoindole-1,3-dione-5-yl) methylene] -2-indolinone
• (XVI.4) 1-acetyl-3- [1-methoxy-1- (3-furyl) methylene] -2-indolinone from 1-acetyl-3- [1-hydroxy-1- (3-furyl) methylene] -2-indolinone
• (XVI.5) 1-acetyl-3- [1-methoxy-1- (2-dibenzylamino-4-oxazolyl) methylene] -2-indolinone from 1-acetyl-3- [1-hydroxy-1- (2- dibenzylamino-4-oxazolyl) methylene] -2-indolinone
• (XVI.6) 1-acetyl-6-methoxycarbonyl-3- [1-methoxy-1- (3,4-ethylenedioxyphenyl) methylene] -2-indolinone from 1-acetyl-6-methoxycarbonyl-3- [1- hydroxy-1- (3,4-ethylenedioxyphenyl) methylene] -2-indolinone
• (XVI.7) 1-Acetyl-6-fluoro-3- [1-methoxy-1- (3,4-ethylenedioxyphenyl) methylene] -2-indolinone from 1-acetyl-6-fluoro-3- [1-hydroxy -1- (3,4-ethylenedioxyphenyl) methylene] -2-indolinone
• (XVI.8) 1-acetyl-3- [1-methoxy-1- (4-methylamino-3-nitrophenyl) methylene] -2-indolinone from 1-acetyl-3- [1-hydroxy-1- (4- methylamino-3-nitrophenyl) methylene] -2-indolinone
• (XVI.9) 1-Acetyl-6-fluoro-3- [1-methoxy-1- (4-methylamino-3-nitrophenyl) methylene] -2-indolinone from 1-acetyl-6-fluoro-3- [1 -hydroxy-1- (4-methylamino-3-nitrophenyl) methylene] -2-indolinone
• (XVI.10) 1-acetyl-6-chloro-3- [1-methoxy-1- (quinazolin-6-yl) -methylene] -2-indolinone from 1-acetyl-6-chloro-3- [1- hydroxy-l- (quinazolin-6-yl) methylene] -2-indolinone
• (XVI.11) 1-acetyl-6-methoxycarbonyl-3- [1-methoxy-1- (3,4-methylenedioxyphenyl) methylene] -2-indolinone from 1-acetyl-6-methoxycarbonyl-3- [1- hydroxy-1- (3,4-methylenedioxyphenyl) methylene] -2-indolinone
• (XVI.12) 1-acetyl-3- [1-methoxy-1- (1-methylbenzotriazol-5-yl) methylene] -2-indolinone from 1-acetyl-3- [1-hydroxy-1- (1- methylbenzotriazole-5-yl) methylene] -2-indolinone

Example XVII

6-chloro-3- {1- [4- (4-methyl-1-piperazinyl-carbonyl) phenylamino] -1- (4-amino-3-nitrophenyl) methylene} -2-indolinone

2.61 g of 1-acetyl-6-chloro-3- [1-chloro-1- (4-acetylamino-3-nitrophenyl) methylene] -2-indolinone, 1.75 g of 4- (4-methyl-1-piperazinyl-carbonyl) aniline and 4.7 ml of ethyldiiso propylamine are heated under reflux in 100 ml of dioxane for 24 hours. The mixture is filtered hot and the filtrate is evaporated to dryness. The residue is dissolved in dichloromethane, extracted three times with water, dried with sodium sulfate and concentrated to dryness. The semi-solid intermediate is dissolved in 10 ml of DMF and 10 ml of methanol and, after addition of 4 ml of 6 molar sodium hydroxide solution, stirred for 2 hours. After adding 300 ml of water, the precipitate is filtered off with suction, dried, stirred with 15 ml of ethyl acetate / methanol / ammonia solution = 85: 15: 1.5, filtered off again and dried at 100 ° C.
Yield: 1.47 g (46% of theory)
R _f value: 0.3 (silica gel, ethyl acetate / methanol / ammonia solution = 80: 20: 2) melting point: 190-195 ° C C ₂₇ H ₂₅ ClN ₆ O ₄ Mass spectrum: m / z = 533/535 [M + H] ⁺

• (XVII.1) 6-Chlor-3-{1-[4-(pyrrolidin-1-ylmethyl)phenylamino]-1-(4-amino-3-nitrophenyl)methylen}-2-indolinon aus 1-Acetyl-6-chlor-3-[1-chlor-1-(4-acetylamino-3-nitrophenyl)methylen]-2-indolinon und 4-(Pyrrolidin-1-ylmethyl)-anilin
• (XVII.2) 6-Chlor-3-{1-(4-[N-(Dimethylaminomethylcarbonyl)-N-methylamino]phenylamino)-1-(4-amino-3-nitrophenyl)methylen}-2-indolinon aus 1-Acetyl-6-chlor-3-[1-chlor-1-(4-acetylamino-3-nitrophenyl)methylen]-2-indolinon und N-(Dimethylaminomethylcarbonyl)-N-methyl-p-phenylendiamin
• (XVII.3) 6-Chlor-3-{1-(4-[N-acetyl-N-(2-dimethylamino-ethyl)amino]phenylamino)-1-(4-amino-3-nitrophenyl)methylen}-2-indolinon aus 1-Acetyl-6-chlor-3-[1-chlor-1-(4-acetylamino-3-nitrophenyl)methylen]-2-indolinon und N-Acetyl-N-(2-dimethylamino-ethyl)-p-phenylendiamin
• (XVII.4) 6-Chlor-3-{1-(4-[N-acetyl-N-(3-dimethylamino-propyl)amino]phenylamino)-1-(4-amino-3-nitrophenyl)methylen}-2-indolinon aus 1-Acetyl-6-chlor-3-[1-chlor-1-(4-acetylamino-3-nitrophenyl)methylen]-2-indolinon und N-Acetyl-N-(3-dimethylamino-propyl)-p-phenylendiamin
• (XVII.5) 6-Chlor-3-{1-(4-[N-methansulfonyl-N-(2-dimethylamino-ethyl)amino]phenylamino)-1-(4-amino-3-nitrophenyl)methylen}-2-indolinon aus 1-Acetyl-6-chlor-3-[1-chlor-1-(4-acetylamino-3-nitrophenyl)methylen]-2-indolinon und N-Methansulfonyl-N-(2-dimethylamino-ethyl)-p-phenylendiamin
• (XVII.6) 3-{1-[4-(Dimethylaminomethyl)phenylamino]-1-(4-amino-3-nitrophenyl)-methylen}-2-indolinon aus 1-Acetyl-3-[1-chlor-1-(4-acetylamino-3-nitrophenyl)methylen]-2-indolinon und 4-(Dimethylaminomethyl)-anilin

The following compounds are prepared analogously to Example XVII:

• (XVII.1) 6-chloro-3- {1- [4- (pyrrolidin-1-ylmethyl) phenylamino] -1- (4-amino-3-nitrophenyl) methylene} -2-indolinone from 1-acetyl-6 -chloro-3- [1-chloro-1- (4-acetylamino-3-nitrophenyl) methylene] -2-indolinone and 4- (pyrrolidin-1-ylmethyl) aniline
• (XVII.2) 6-chloro-3- {1- (4- [N- (dimethylaminomethylcarbonyl) -N-methylamino] phenylamino) -1- (4-amino-3-nitrophenyl) methylene} -2-indolinone from 1 -Acetyl-6-chloro-3- [1-chloro-1- (4-acetylamino-3-nitrophenyl) methylene] -2-indolinone and N- (dimethylaminomethylcarbonyl) -N-methyl-p-phenylenediamine
• (XVII.3) 6-chloro-3- {1- (4- [N-acetyl-N- (2-dimethylamino-ethyl) amino] phenylamino) -1- (4-amino-3-nitrophenyl) methylene} - 2-indolinone from 1-acetyl-6-chloro-3- [1-chloro-1- (4-acetylamino-3-nitrophenyl) methylene] -2-indolinone and N-acetyl-N- (2-dimethylamino-ethyl) -p-phenylenediamine
• (XVII.4) 6-chloro-3- {1- (4- [N-acetyl-N- (3-dimethylamino-propyl) amino] phenylamino) -1- (4-amino-3-nitrophenyl) methylene} - 2-indolinone from 1-acetyl-6-chloro-3- [1-chloro-1- (4-acetylamino-3-nitrophenyl) methylene] -2-indolinone and N-acetyl-N- (3-dimethylamino-propyl) -p-phenylenediamine
• (XVII.5) 6-chloro-3- {1- (4- [N-methanesulfonyl-N- (2-dimethylamino-ethyl) amino] phenylamino) -1- (4-amino-3-nitrophenyl) methylene} - 2-indolinone from 1-acetyl-6-chloro-3- [1-chloro-1- (4-acetylamino-3-nitrophenyl) methylene] -2-indolinone and N-methanesulfonyl-N- (2-dimethylamino-ethyl) -p-phenylenediamine
• (XVII.6) 3- {1- [4- (Dimethylaminomethyl) phenylamino] -1- (4-amino-3-nitrophenyl) -methylene} -2-indolinone from 1-acetyl-3- [1-chloro-1 - (4-acetylamino-3-nitrophenyl) methylene] -2-indolinone and 4- (dimethylaminomethyl) aniline

Example XVIII

6-chloro-3- {1- [4- (4-methyl-1-piperazinyl-carbonyl) phenylamino] -1- (3,4-diaminophenyl) methylene} -2-indolinone

0.746 g of 6-chloro-3- {1- [4- (4-methyl-1-piperazinylcarbonyl) phenylamino] -1- (4-amino-3-nitrophenyl) methylene} -2-indolinone are dissolved in 30 ml of acetic acid hydrogenated for 4 hours with the addition of 0.60 g of Raney nickel under 50 psi of hydrogen pressure. After the addition of a further 0.30 g of Raney nickel, the mixture is hydrogenated under the same conditions for a further 4 hours, then the catalyst is filtered off with suction. The residue obtained from the filtrate by distilling off the solvent is dissolved in water and the solution is made alkaline with sodium carbonate solution. The precipitated crude product is filtered off with suction, washed with water, dried, dissolved in 70 ml dichloromethane / methanol / ammonia solution = 70: 30: 3 and filtered through a layer of silica gel. The filtrate is evaporated, the residue is stirred with 5 ml of ethyl acetate, suction filtered and dried at 80 ° C.
Yield: 0.60 g (85% of theory)
R _f value: 0.4 (silica gel, dichloromethane / methanol / ammonia solution = 85: 15: 1.5) C ₂₇ H ₂₇ ClN ₆ O ₂ Mass spectrum: m / z = 503/505 [M + H] ⁺

• (XVIII.1) 6-Chlor-3-{1-[4-(pyrrolidin-1-ylmethyl)phenylamino]-1-(3,4-diaminophenyl)-methylen}-2-indolinon aus 6-Chlor-3-{1-[4-(pyrrolidin-1-ylmethyl)phenylamino]-1-(4-amino-3-nitrophenyl)-methylen}-2-indolinon
• (XVIII.2) 6-Chlor-3-{1-(4-[N-(Dimethylaminomethylcarbonyl)-N-methyl-amino]phenylamino)-1-(3,4-diaminophenyl)methylen}-2-indolinon aus 6-Chlor-3-{1-(4-[N-(Dimethylaminomethylcarbonyl)-N-methyl-amino]phenyl- amino)-1-(4-amino-3-nitrophenyl)methylen}-2-indolinon
• (XVIII.3) 6-Chlor-3-{1-(4-[N-acetyl-N-(2-dimethylamino-ethyl)amino]phenylamino)-1-(3,4-diaminophenyl)methylen}-2-indolinon aus 6-Chlor-3-{1-(4-[N-acetyl-N-(2-dimethylamino-ethyl)amino]phenylamino)-1-(4-amino-3-nitrophenyl)methylen}-2-indolinon
• (XVIII.4) 6-Chlor-3-{1-(4-[N-acetyl-N-(3-dimethylamino-propyl)amino]phenylamino)-1-(3,4-diaminophenyl)methylen}-2-indolinon aus 6-Chlor-3-{1-(4-[N-acetyl-N-(3-dimethylamino-propyl)amino]phenylamino)-1-(4-amino-3-nitrophenyl)methylen}-2-indolinon

The following compounds are prepared analogously to Example XVIII:

• (XVIII.1) 6-chloro-3- {1- [4- (pyrrolidin-1-ylmethyl) phenylamino] -1- (3,4-diaminophenyl) -methylene} -2-indolinone from 6-chloro-3- {1- [4- (pyrrolidin-1-ylmethyl) phenylamino] -1- (4-amino-3-nitrophenyl) methylene} -2-indolinone
• (XVIII.2) 6-chloro-3- {1- (4- [N- (dimethylaminomethylcarbonyl) -N-methylamino] phenylamino) -1- (3,4-diaminophenyl) methylene} -2-indolinone from 6 -Chlor-3- {1- (4- [N- (dimethylaminomethylcarbonyl) -N-methylamino] phenylamino) -1- (4-amino-3-nitrophenyl) methylene} -2-indolinone
• (XVIII.3) 6-chloro-3- {1- (4- [N-acetyl-N- (2-dimethylamino-ethyl) amino] phenylamino) -1- (3,4-diaminophenyl) methylene} -2- indolinone from 6-chloro-3- {1- (4- [N-acetyl-N- (2-dimethylamino-ethyl) amino] phenylamino) -1- (4-amino-3-nitrophenyl) methylene} -2-indolinone
• (XVIII.4) 6-chloro-3- {1- (4- [N-acetyl-N- (3-dimethylamino-propyl) amino] phenylamino) -1- (3,4-diaminophenyl) methylene} -2- indolinone from 6-chloro-3- {1- (4- [N-acetyl-N- (3-dimethylamino-propyl) amino] phenylamino) -1- (4-amino-3-nitrophenyl) methylene} -2-indolinone

Example XIX

1-Acetyl-6-fluoro-3- [1-methoxy-1- (1-methylbenzimidazol-5-yl) methylene] -2-indolinone

0.40 g of 1-acetyl-6-fluoro-3- [1-methoxy-1- (4-methylamino-3-nitrophenyl) methylene] -2-indolinone are dissolved in 5.0 ml of formic acid with the addition of 0.20 g of Raney nickel for 3 hours 50 psi hydrogen atmosphere hydrogenated. The catalyst is suctioned off and the filtrate is concentrated. The residue is stirred with diethyl ether, suction filtered after crystallization and dried.
Yield: 0.30 g (79% of theory)
R _f value: 0.8 (silica gel, dichloromethane / methanol / concentrated ammonia = 90: 10: 1) C ₂₀ H ₁₆ FN ₃ O ₃ Mass spectrum: m / z = 366 [M ⁺ H] ⁺

• (XIX.1) 1-Acetyl-3-[1-methoxy-1-(1-methylbenzimidazol-5-yl)methylen]-2-indolinon aus 1-Acetyl-3-[1-methoxy-1-(4-methylamino-3-nitrophenyl)methylen]-2-indolinon

The following connection is established analogously to example XIX:

• (XIX.1) 1-acetyl-3- [1-methoxy-1- (1-methylbenzimidazol-5-yl) methylene] -2-indolinone from 1-acetyl-3- [1-methoxy-1- (4- methylamino-3-nitrophenyl) methylene] -2-indolinone

Example XX:

4- (1-methyl-4-piperazinyl-carbonyl) -1-nitrobenzene

A solution of 20.0 g of 4-nitrobenzoyl chloride in 100 ml of dichloromethane is added dropwise to a solution of 12.0 ml of N-methylpiperazine and 30 ml of triethylamine in 600 ml of dichloromethane at room temperature. The reaction solution is stirred for one hour, then washed three times with water, dried with sodium sulfate and concentrated to dryness. The residue is stirred with tert-butyl methyl ether and dried at 40 ° C.
Yield: 16.7 g (62% of theory)
R _f value: 0.35 (silica gel, dichloromethane / methanol = 9: 1) C ₁₂ H ₁₅ N ₃ O ₃ Mass spectrum: m / z = 250 [M + H] ⁺

• (XX.1) 4-[N-Methyl-N-(1-methyl-4-piperidinyl)-aminocarbonyl]-1-nitrobenzol aus 4-Nitrobenzoylchlorid und 1-Methyl-4-methylamino-piperidin
• (XX.2) 4-[N-Methyl-N-(2-dimethylamino-ethyl)-aminocarbonyl]-1-nitrobenzol aus 4-Nitrobenzoylchlorid und N,N,N'-Trimethyl-l,2-diaminoethan, wobei auf das Ausrühren mit tert-Butylmethylether verzichtet wird.
• (XX.3) 4-[N-Methyl-N-(3-dimethylamino-propyl)-aminocarbonyl]-1-nitrobenzol aus 4-Nitrobenzoylchlorid und N,N,N'-Trimethyl-1,3-diaminopropan, wobei auf das Ausrühren mit tert-Butylmethylether verzichtet wird.
• (XX.4) 4-(1-Methyl-4-piperazinyl-carbonyl-methyl)-1-nitrobenzol aus 4-Nitrophenylacetyichlorid und 1-Methylpiperazin
• (XX.5) 4-(Dimethylamino-carbonyl)-1-nitrobenzol aus 4-Nitrobenzoylchlorid und Dimethylamin hydrochlorid
• (XX.6) 4-[N-Methyl-N-(2-dimethylamino-ethyl)-aminosulfonyl]-1-nitrobenzol aus 4-Nitrobenzolsulfonylchlorid und N,N,N'-Trimethyl-1,2-diaminoethan, wobei auf das Ausrühren mit tert-Butylmethylether verzichtet wird.
• (XX.7) 4-[N-Methyl-N-(3-dimethylamino-propyl)-aminosulfonyl]-1-nitrobenzol aus 4-Nitrobenzolsulfonylchlorid und N,N,N'-Trimethyl-1,3-diaminopropan, wobei auf das Ausrühren mit tert-Butylmethylether verzichtet wird.
• (XX.8) 4-[N-Ethyl-N-(2-dimethylamino-ethyl)-aminocarbonyl]-1-nitrobenzol aus 4-Nitrobenzoylchlorid und N-Ethyl,N',N'-Dimethyl-1,2-diaminoethan, wobei auf das Ausrühren mit tert-Butylmethylether verzichtet wird.
• (XX.9) 3-[N-Methyl-N-(2-dimethylamino-ethyl)-aminocarbonyl]-1-nitrobenzol aus 3-Nitrobenzoylchlorid und N,N,N'-Trimethyl-1,2-diaminoethan
• (XX.10) 4-(1-t-Butoxycarbonyl-4-piperazinyl-carbonyl)-nitrobenzol aus 3-Nitrobenzoylchlorid und 1-t-Butoxycarbonyl-piperazins
• (XX.11) 4-(1-t-Butoxycarbonyl-perhydro-1,4-diazepin-4-yl-carbonyl)-nitrobenzol aus 3-Nitrobenzoylchlorid und 1-t-Butoxycarbonyl-perhydro-1,4-diazepin
• (XX.12) 4-[N-Methyl-N-(2-{N'-methyl-N'-t-butoxycarbonyl-amino}-ethyl)-aminocarbonyl]-1-nitrobenzol aus 4-Nitrobenzoylchlorid und N,N'-Dimethyl-N-t-butoxycarbonyl-1,2-diaminoethan

The following compounds are prepared analogously to Example XX:

• (XX.1) 4- [N-Methyl-N- (1-methyl-4-piperidinyl) aminocarbonyl] -1-nitrobenzene from 4-nitrobenzoyl chloride and 1-methyl-4-methylamino-piperidine
• (XX.2) 4- [N-Methyl-N- (2-dimethylamino-ethyl) aminocarbonyl] -1-nitrobenzene from 4-nitrobenzoyl chloride and N, N, N'-trimethyl-1,2-diaminoethane, where on stirring with tert-butyl methyl ether is dispensed with.
• (XX.3) 4- [N-Methyl-N- (3-dimethylamino-propyl) -aminocarbonyl] -1-nitrobenzene from 4-nitrobenzoyl chloride and N, N, N'-trimethyl-1,3-diaminopropane, where on stirring with tert-butyl methyl ether is dispensed with.
• (XX.4) 4- (1-methyl-4-piperazinyl-carbonyl-methyl) -1-nitrobenzene from 4-nitrophenylacetyichloride and 1-methylpiperazine
• (XX.5) 4- (Dimethylamino-carbonyl) -1-nitrobenzene from 4-nitrobenzoyl chloride and dimethylamine hydrochloride
• (XX.6) 4- [N-Methyl-N- (2-dimethylamino-ethyl) -aminosulfonyl] -1-nitrobenzene from 4-nitrobenzenesulfonyl chloride and N, N, N'-trimethyl-1,2-diaminoethane, where on stirring with tert-butyl methyl ether is dispensed with.
• (XX.7) 4- [N-Methyl-N- (3-dimethylamino-propyl) -aminosulfonyl] -1-nitrobenzene from 4-nitrobenzenesulfonyl chloride and N, N, N'-trimethyl-1,3-diaminopropane, whereby on stirring with tert-butyl methyl ether is dispensed with.
• (XX.8) 4- [N-ethyl-N- (2-dimethylamino-ethyl) aminocarbonyl] -1-nitrobenzene from 4-nitrobenzoyl chloride and N-ethyl, N ', N'-dimethyl-1,2-diaminoethane , the stirring with tert-butyl methyl ether being dispensed with.
• (XX.9) 3- [N-Methyl-N- (2-dimethylaminoethyl) aminocarbonyl] -1-nitrobenzene from 3-nitrobenzoyl chloride and N, N, N'-trimethyl-1,2-diaminoethane
• (XX.10) 4- (1-t-Butoxycarbonyl-4-piperazinyl-carbonyl) -nitrobenzene from 3-nitrobenzoyl chloride and 1-t-butoxycarbonyl-piperazine
• (XX.11) 4- (1-t-Butoxycarbonyl-perhydro-1,4-diazepin-4-yl-carbonyl) -nitrobenzene from 3-nitrobenzoyl chloride and 1-t-butoxycarbonyl-perhydro-1,4-diazepine
• (XX.12) 4- [N-Methyl-N- (2- {N'-methyl-N'-t-butoxycarbonylamino} ethyl) aminocarbonyl] -1-nitrobenzene from 4-nitrobenzoyl chloride and N, N '-dimethyl-N-t-butoxycarbonyl-1,2-diaminoethane

Example XXI:

4- (1-methyl-4-piperazinyl-carbonyl) aniline

10.9 g of 4- (1-methyl-4-piperazinyl-carbonyl) -1-nitrobenzene are hydrogenated in 90 ml of ethanol with the addition of 1.1 g of Raney nickel for 35 minutes at room temperature under a 50 psi hydrogen atmosphere. The catalyst is filtered off with suction, the filtrate is concentrated, the residue is stirred with diethyl ether and dried.
Yield: 8.43 g (88% of theory)
R _f value: 0.30 (silica gel, dichloromethane / methanol = 9: 1) C ₁₂ H ₁₇ N ₃ O Mass spectrum: m / z = 220 [M + H] ⁺

The following are analogous to Example XXI Connections established:

• (XXI.1) 4- [N-Methyl-N- (1-methyl-4-piperidinyl) aminocarbonyl] aniline from 4- [N-methyl-N- (1-methyl-4-piperidinyl) aminocarbonyl] -1-nitrobenzene
• (XXI.2) 4- [N-Methyl-N- (2-dimethylaminoethyl) aminocarbonyl] -1-aniline 4- [N-methyl-N- (2-dimethylamino-ethyl) aminocarbonyl] -1-nitrobenzene, being on stirring with diethyl ether is dispensed with.
• (XXI.3) 4- [N-Methyl-N- (3-dimethylaminopropyl) aminocarbonyl] -1-aniline from 4- [N-methyl-N- (3-dimethylamino-propyl) aminocarbonyl] -1-nitrobenzene, being on stirring with diethyl ether is dispensed with.
• (XXI.4) 4- (1-methyl-4-piperazinyl-carbonyl-methyl) aniline 4- (1-methyl-4-piperazinyl-carbonyl-methyl) -1-nitrobenzene
• (XXI.5) N-methoxyacetyl-N-methyl-4-amino-aniline from N-methoxyacetyl-N-methyl-4-amino-nitrobenzene
• (XXI.6) N-acetyl-N-methyl-4-amino-aniline from N-acetyl-N-methyl-4-amino-nitrobenzene
• (XXI.7) 4- (Dimethylamino-carbonyl) aniline from 4- (dimethylamino-carbonyl) -1-nitrobenzene
• (XXI.8) 1- (4-aminophenyl) -3,5-dimethylpyrazole from 1- (4-nitrophenyl) -3,5-dimethylpyrazole, which is represented as described in: K. v. Auwers, A. Kreuder, Chem. Ber. 58 (1925) 1981
• (XXI.9) 4- [N-Methyl-N- (2-dimethylamino-ethyl) aminosulfonyl] -1-aniline from 4- [N-methyl-N- (2-dimethylamino-ethyl) -aminosulfonyl] -1-nitrobenzene, being on stirring with diethyl ether is dispensed with.
• (XXI.10) N-4-aminobenzoyl-N-methylaminoacetonitrile (prepared from N-4-nitrobenzoyl-N-methylaminoacetonitrile ( as described in: D. Clerin et al., Tetrahedron 32 (1976) 1055-1059), Pd / C (5%) as catalyst and ethyl acetate as solvent becomes.
• (XXI.11) 4- [N-Methyl-N- (3-dimethylamino-propyl) -aminosulfonyl] -1-aniline from 4- [N-methyl-N- (3-dimethylamino-propyl) -aminosulfonyl] -1-nitrobenzene, being on stirring with diethyl ether is dispensed with.
• (XXI.12) 4- [N-Ethyl-N- (2-dimethylaminoethyl) aminocarbonyl] aniline from 4- [N-ethyl-N- (2-dimethylamino-ethyl) aminocarbonyl] -1-nitrobenzene, being on stirring with diethyl ether is dispensed with.
• (XXI.13) 3- [N-Methyl-N- (2-dimethylaminoethyl) aminocarbonyl] aniline from 3- [N-methyl-N- (2-dimethylamino-ethyl) aminocarbonyl] -1-nitrobenzene
• (XXI.14) 4- (1-t-Butoxycarbonyl-4-piperazinylcarbonyl) aniline from 4- (1-t-butoxycarbonyl-4-piperazinyl-carbonylj-nitrobenzene
• (XXI.15) 4- (1-t-Butoxycarbonyl-perhydro-1,4-diazepin-4-yl-carbonyl) aniline from 4- (1-t-butoxycarbonyl-perhydro-1,4-diazepin-4-yl-carbonyl) nitrobenzene
• (XXI.16) 4- [N-Methyl-N- (2- {N'-methyl-N'-t-butoxycarbonylamino} ethyl) aminocarbonyl] aniline from 4- [N-methyl-N- (2- {N'-methyl-N'-t-butoxycarbonylamino} ethyl) aminocarbonyl] -1-nitrobenzene

• (XXII) N-Acetyl-N-methyl-p-phenylendiamin wird dargestellt wie beschrieben in: G.T. Morgan, W.R. Grist, J. Chem. Soc. 113 (1918) 688-694
• (XXIII) 4-(2-Dimethylamino-ethoxy)-anilin wird dargestellt wie beschrieben in: D.H. Hunter et al., Can. J. Chem. 62 (1984) 2015-2019
• (XXIV) 4-(2-Diethylamino-ethylsulfonyl)-anilin wird dargestellt wie beschrieben in: J. Walker, J. Chem. Soc. (1945) 630-633

The syntheses of the following compounds are known from the literature:

• (XXII) N-acetyl-N-methyl-p-phenylenediamine is represented as described in: GT Morgan, WR Grist, J. Chem. Soc. 113 (1918) 688-694
• (XXIII) 4- (2-dimethylaminoethoxy) aniline is shown as described in: DH Hunter et al., Can. J. Chem. 62 (1984) 2015-2019
• (XXIV) 4- (2-Diethylamino-ethylsulfonyl) aniline is prepared as described in: J. Walker, J. Chem. Soc. (1945) 630-633

• (XXIV.1) 4-Methylsulfonyl-anilin aus 4-Acetamidophenylsulfinsäure und Dimethylsulfat

The following connection is established analogously to Example XXIV:

• (XXIV.1) 4-methylsulfonyl-aniline from 4-acetamidophenylsulfinic acid and dimethyl sulfate

• (XXV) 4-(Pyrrolidin-1-ylmethyl)anilin
• (XXV.1) N-(Dimethylaminomethylcarbonyl)-N-methyl-p-phenylendiamin
• (XXV.2) N-Methyl-N-[(1-methylpiperazin-4-yl)methylcarbonyl]-p-phenylendiamin
• (XXV.3) N-Acetyl-N-(2-dimethylamino-ethyl)-p-phenylendiamin
• (XXV.4) N-Acetyl-N-(3-dimethylamino-propyl)-p-phenylendiamin
• (XXV.5) N-Propionyl-N-(3-dimethylamino-propyl)-p-phenylendiamin wird analog Verbindung XXV.4 hergestellt.
• (XXV.6) N-Methansulfonyl-N-(2-dimethylamino-ethyl)-p-phenylendiamin
• (XXV.7) N-Propansulfonyl-N-(2-dimethylamino-ethyl)-p-phenylendiamin
• (XXV.8) 4-(Dimethylaminomethyl)-anilin
• (XXV.9) N-(2-Dimethylamino-ethyl)-N-(pyridin-3-carbonyl)-p-phenylendiamin
• (XXV.10) 4-(N-Ethyl-N-methyl-aminomethyl)-anilin
• (XXV.11) 4-[(4-Methylpiperazin-1-yl)-methyl]-anilin
• (XXV.12) 4-(N-Ethyl-N-terf-butoxycarbonyl-aminomethyl)-anilins
• (XXV.13) 4-(N-Methyl-N-tert-butoxycarbonyl-aminomethyl)-anilins
• (XXV.14) 4-{[1-(tert-Butoxycarbonyl)-piperazin-4-yl]-methyl}-anilin
• (XXV.15) 4-(1-Methylimidazol-2-yl)-anilin
• (XXV.16) 4-(Diethylaminomethyl)-anilin
• (XXV.17) 4-(1,2,4-Triazol-1-yl-methyl)-anilin
• (XXV.18) 4-(1,2,3-Triazol-1-yl-methyl)-anilin
• (XXV.19) 4-(1,2,3-Triazol-2-yl-methyl)-anilin
• (XXV.20) N-Methansulfonyl-N-methyl-p-phenylendiamin
• (XXV.21) N-Methansulfonyl-N-(2-trifluoracetylamino-ethyl)-p-phenylendiamin
• (XXV.22) 4-(4-Hydroxypiperidin-1-yl-methyl)-anilin
• (XXV.23) N-[(2-Dimethylamino-ethyl)-carbonyl]-N-methyl-p-phenylendiamin
• (XXV.24) 4-[N-(2-Hydroxyethyl)-N-methyl-amino-methyl]-anilin
• (XXV.25) (R)-4-(3-Hydroxypyrrolidin-1-yl-methyl)-anilin wird dargestellt wie die beschriebene racemische Verbindung, wobei (R)-3-Hydroxypyrrolidin eingesetzt wird.
• (XXV.26) (S)-4-(3-Hydroxypyrrolidin-1-yl-methyl)-anilin wird dargestellt wie die beschriebene racemische Verbindung, wobei (S)-3-Hydroxypyrrolidin eingesetzt wird.
• (XXV.27) N-Ethansulfonyl-N-(2-dimethylamino-ethyl)-p-phenylendiamin
• (XXV.28) N-Prupionyl-N-(3-dimethylamino-propyl)-p-phenylendiamin wird dargestellt analog Verbindung XXV.4, wobei Propionsäureanhydrid anstelle von Essigsäureanhydrid verwendet wird.
• (XXV.29) N-Propionyl-N-(2-dimethylamino-ethyl)-p-phenylendiamin
• (XXV.30) 4-(1-Ethylimidazol-2-yl)-anilin
• (XXV.31) 4-[N-(2-Methoxyethyl)-N-methyl-amino-methyl]-anilin
• (XXV.32) (S)-4-([2-Hydroxymethyl-pyrrollidin-1-yl]-methyl)-anilin wird dargestellt analog der beschriebenen Verbindung 4-(3-Hydroxypyrrolidin-1-yl-methyl)-anilin ausgehend von (S)-Prolinol und 4-Nitrobenzylbromid
• (XXV.33) 4-(Morpholin-4-yl-methyl)-anilin
• (XXV.34) 4-(N-Isobutyl-N-tert-butoxycarbonyl-aminomethyl)-anilin wird dargestellt analog Verbindung XXV.12, wobei Isobutylamin anstelle von Ethylamin verwendet wird.
• (XXV.35) N-Methansulfonyl-N-(2-dimethylamino-ethyl)-3-chlor-p-phenylendiamin

The syntheses of the following compounds are described in WO 01/27081:

• (XXV) 4- (pyrrolidin-1-ylmethyl) aniline
• (XXV.1) N- (dimethylaminomethylcarbonyl) -N-methyl-p-phenylenediamine
• (XXV.2) N-methyl-N - [(1-methylpiperazin-4-yl) methylcarbonyl] -p-phenylenediamine
• (XXV.3) N-acetyl-N- (2-dimethylamino-ethyl) -p-phenylenediamine
• (XXV.4) N-acetyl-N- (3-dimethylamino-propyl) -p-phenylenediamine
• (XXV.5) N-propionyl-N- (3-dimethylamino-propyl) -p-phenylenediamine is prepared analogously to compound XXV.4.
• (XXV.6) N-methanesulfonyl-N- (2-dimethylamino-ethyl) -p-phenylenediamine
• (XXV.7) N-propanesulfonyl-N- (2-dimethylamino-ethyl) -p-phenylenediamine
• (XXV.8) 4- (dimethylaminomethyl) aniline
• (XXV.9) N- (2-Dimethylamino-ethyl) -N- (pyridine-3-carbonyl) -p-phenylenediamine
• (XXV.10) 4- (N-ethyl-N-methylaminomethyl) aniline
• (XXV.11) 4 - [(4-methylpiperazin-1-yl) methyl] aniline
• (XXV.12) 4- (N-ethyl-N-tert-butoxycarbonylaminomethyl) aniline
• (XXV.13) 4- (N-methyl-N-tert-butoxycarbonylaminomethyl) aniline
• (XXV.14) 4 - {[1- (tert-Butoxycarbonyl) piperazin-4-yl] methyl} aniline
• (XXV.15) 4- (1-methylimidazol-2-yl) aniline
• (XXV.16) 4- (diethylaminomethyl) aniline
• (XXV.17) 4- (1,2,4-triazol-1-ylmethyl) aniline
• (XXV.18) 4- (1,2,3-triazol-1-ylmethyl) aniline
• (XXV.19) 4- (1,2,3-triazol-2-ylmethyl) aniline
• (XXV.20) N-methanesulfonyl-N-methyl-p-phenylenediamine
• (XXV.21) N-methanesulfonyl-N- (2-trifluoroacetylamino-ethyl) -p-phenylenediamine
• (XXV.22) 4- (4-hydroxypiperidin-1-ylmethyl) aniline
• (XXV.23) N - [(2-dimethylaminoethyl) carbonyl] -N-methyl-p-phenylenediamine
• (XXV.24) 4- [N- (2-Hydroxyethyl) -N-methylamino-methyl] aniline
• (XXV.25) (R) -4- (3-hydroxypyrrolidin-1-yl-methyl) -aniline is prepared like the racemic compound described, using (R) -3-hydroxypyrrolidine.
• (XXV.26) (S) -4- (3-hydroxypyrrolidin-1-yl-methyl) -aniline is prepared like the racemic compound described, using (S) -3-hydroxypyrrolidine.
• (XXV.27) N-ethanesulfonyl-N- (2-dimethylamino-ethyl) -p-phenylenediamine
• (XXV.28) N-Prupionyl-N- (3-dimethylamino-propyl) -p-phenylenediamine is prepared analogously to compound XXV.4, propionic anhydride being used instead of acetic anhydride.
• (XXV.29) N-Propionyl-N- (2-dimethylamino-ethyl) -p-phenylenediamine
• (XXV.30) 4- (1-ethylimidazol-2-yl) aniline
• (XXV.31) 4- [N- (2-methoxyethyl) -N-methylamino-methyl] aniline
• (XXV.32) (S) -4 - ([2-hydroxymethyl-pyrrollidin-1-yl] methyl) aniline is prepared analogously to the compound 4- (3-hydroxypyrrolidin-1-yl-methyl) aniline starting from of (S) -prolinol and 4-nitrobenzyl bromide
• (XXV.33) 4- (Morpholin-4-ylmethyl) aniline
• (XXV.34) 4- (N-isobutyl-N-tert-butoxycarbonylaminomethyl) aniline is prepared analogously to compound XXV.12, isobutylamine being used instead of ethylamine.
• (XXV.35) N-methanesulfonyl-N- (2-dimethylamino-ethyl) -3-chloro-p-phenylenediamine

Example XXVI:

N-methoxyacetyl-N-methyl-4-amino-nitrobenzene

A suspension of 15.4 g of N-methyl-4-nitroaniline in 100 ml of tetrahydrofuran and 38.5 ml of triethylamine is mixed dropwise with a solution of 10.0 g of methoxyacetyl chloride in 30 ml of THF. The reaction mixture is stirred for 15 hours, then another 10 g of methoxyacetyl chloride in 30 ml of THF are added. After a further 5 hours, the solvent is distilled off, the residue is taken up in dichloromethane and extracted twice with dilute hydrochloric acid. The organic phase is dried over magnesium sulfate and concentrated. The residue is purified chromatographically on silica gel (mobile phase: dichloromethane / ethyl acetate 9: 1, then 8: 2).
Yield: 19.2 g (93% of theory)
R _f value: 0.66 (silica gel, ethyl acetate / methanol = 9: 1) C ₁₀ H ₁₂ N ₂ O ₄ Mass spectrum: m / z = 225 [M + H] ⁺ ; 247 [M + Na] ⁺

• (XXVI.1) N-Acetyl-N-methyl-4-amino-nitrobenzol

The following connection is established analogously to Example XXVI:

• (XXVI.1) N-acetyl-N-methyl-4-amino-nitrobenzene

• (XXVII) N-(4-Aminophenyl)-2-pyrrolidon wird dargestellt wie beschrieben in: W. Reppe et al., Justus Liebigs Ann. Chem. 596 (1955) 204
• (XXVIII) (4-Aminobenzyl)-pyridin-2-yl-amin wird dargestellt wie beschrieben in: V. Martinez-Barrasa, et al., Tetrahedron 56 (2000) 2481-2490

The syntheses of the following compounds are known from the literature:

• (XXVII) N- (4-aminophenyl) -2-pyrrolidone is represented as described in: W. Reppe et al., Justus Liebigs Ann. Chem. 596 (1955) 204
• (XXVIII) (4-aminobenzyl) pyridin-2-yl-amine is prepared as described in: V. Martinez-Barrasa, et al., Tetrahedron 56 (2000) 2481-2490

Example XXIX:

N- [2- (dimethylamino) ethyl] -sufanilsäureamid

5.26 g of sulfanilic acid fluoride and 16.5 ml of N, N-dimethyl-ethylenediamine are stirred for 4 hours at 100 ° C., then dissolved in ethyl acetate and extracted three times with saline. The residue obtained by concentrating the organic phase is crystallized from diethyl ether and dried at 60 ° C.
Yield: 4.1 g (56% of theory)
Melting point: 86-88 ° C C ₁₀ H ₁₇ N ₃ O ₂ S Mass spectrum: m / z = 244 [M + H] ⁺ ; 242 [MH] ^-

• (XXIX.1) N-[3-(Dimethylamino)-propyl]-sufanilsäureamid aus Sulfanilsäurefluorid und N,N-Dimethyl-1,3-diaminopropan

The following connection is established analogously to example XXIX:

• (XXIX.1) N- [3- (dimethylamino) propyl] sulfanic acid amide from sulfanilic acid fluoride and N, N-dimethyl-1,3-diaminopropane

• (XXX) N-(Dimethylaminomethylcarbonyl)-N-methyl-3-methoxy-p-phenylendiamin

The synthesis of the following compound is described in international application WO 01/27081:

• (XXX) N- (dimethylaminomethylcarbonyl) -N-methyl-3-methoxy-p-phenylenediamine

Making the end connections:

Example 1.0

3- (Z) - [1- {4- [N-propionyl-N- (3-dimethylamino-propyl) -amino] -phenylamino} -1- (2-dibenzylamino-4-oxazolyl) methylene] -2- indolinone

0.935 g of 1-acetyl-3- [1-methoxy-1- (2-dibenzylamino-4-oxazolyl) methylene] -2-indolinone (educt XVI.5) and 0.549 g of N-propionyl-N- (3-dimethylamino -propyl) -p-phenylenediamine (educt XXV.5) are dissolved in 10 ml of dimethylformamide and stirred at 120 ° C. for 3 hours. After cooling, 5 ml of methanol and 2 ml of 2 molar sodium hydroxide solution are added and the mixture is stirred for a further hour at room temperature. After adding 60 ml of water, extracted twice with ethyl acetate. The residue obtained from the combined organic phases by removing the solvent is washed over a silica gel column with dichloromethane / methanol / conc. Ammonia = 90: 10: 1 as the eluent, purified by chromatography. The crude product obtained in this way is stirred with ice-cold diethyl ether, suction filtered and dried at 80.degree.
Yield: 0.40 g (31% of theory)
R _f value: 0.5 (silica gel, methylene chloride / methanol / concentrated ammonia = 85: 15: 1.5)
Mp: 204-205 ° C C ₄₀ H ₄₂ N ₆ O ₃ Mass spectrum: m / z = 655 [M + H] ⁺ ; m / z = 653 [MH] ^-

Analogously to Example 1.0, the following compounds of the general formula I.1 are prepared from the starting materials indicated in each case:

Also be analogous to Example 1 established the following connections:

(1,129) 6-Fluoro-3- (Z) - [1- (3- {N- (2-dimethylaminoethyl) -N-methylaminocarbonyl} phenylamino) -1- (1-methylbenzimidazol-5-yl) methylene ] -2-indolinone from the starting materials XIX and XXI.13
R _f value: 0.6 (silica gel, methylene chloride / methanol / concentrated ammonia = 80: 20: 1)
Mp: 131-138 ° C C ₂₉ H ₂₉ FN ₆ O ₂ Mass spectrum: m / z = 513 [M + H] ⁺

(1,130) 6-Chloro-3- (Z) - [1- (4- {N- (2-dimethylaminoethyl) -N-methanesulfonylamino} -3-chlorophenylamino) -1- (1,2 -ethylenedioxyphen-4-yl) -methylene] -2-indolinone from the educts XVI.1 and XXV.35
R _f value: 0.2 (silica gel, methylene chloride / methanol = 9: 1)
Mp: 153 ° C C ₂₈ N ₂₈ Cl ₂ N ₄ O ₅ S Mass spectrum: m / z = 601/603/605 [M + H] ⁺

(1,131) 6-Chloro-3- (Z) - {1- [4- (N-dimethylaminomethylcarbonyl-N-methylamino) -3-methoxyphenylamino] -1- (1,2-ethylenedioxyphen-4-yl ) -methylene} -2-indolinone from the educts XVI.1 and XXX
R _f value: 0.3 (silica gel, methylene chloride / methanol / concentrated ammonia = 90: 10: 1)
Mp: 229 ° C C ₂₉ N ₂₉ ClN ₄ O ₅ Mass spectrum: m / z = 549/551 [M + H] ⁺

(1,132) 6-Fluoro-3- (Z) - {1- [4- (N-dimethylaminomethylcarbonyl-N-methylamino) -3-methoxyphenylamino] -1- (1,2-ethylenedioxyphen-4-yl ) -methylene} -2-indolinone from the educts XVI.7 and XXX
R _f value: 0.3 (silica gel, methylene chloride / methanol = 9: 1)
Mp: 142 ° C C ₂₉ H ₂₉ FN ₄ O ₅ Mass spectrum: m / z = 533 [M + H] ⁺

(1.133) 6-Fluoro-3- (Z) - [1- (4- {N- (2-dimethylaminoethyl) -N-methanesulfonylamino} -3-chlorophenylamino) -1- (1,2 -ethylenedioxyphen-4-yl) -methylene] -2-indolinone from the educts XVI.7 and XXV.35
R _f value: 0.2 (silica gel, methylene chloride / methanol = 9: 1)
Mp: 173 ° C C ₂₈ H ₂₈ ClFN ₄ O ₅ S Mass spectrum: m / z = 687/589 [M + H] ⁺

Example 2.0

3- (Z) - {1- [4- (N-Dimethylaminomethylcarbonyl-N-methyl-amino) -phenylamino] -1- (2-pyrazinyl) methylene} -2-indolinone

0.281 g of 1-acetyl-3- (1-hydroxy-1- (2-pyrazinyl) -methylene-2-indolinone (starting material X) and 0.416 g of phosphorus pentachloride are refluxed in 10 ml of dioxane for 3 hours. Volatile constituents are distilled off, the residue was taken up in 15 ml of dioxane and, after addition of 0.415 g of N- (dimethylaminomethylcarbonyl) -Nmethyl-p-phenylenediamine (educt XXV.1), again heated under reflux for 5 hours, after which 50 ml of water had been added and the mixture was extracted five times with dichloromethane The residue obtained from the combined organic phases dried over magnesium sulfate by distilling off the solvent is purified chromatographically on a silica gel column using dichloromethane / methanol / concentrated ammonia = 190: 10: 1 dried at 80 ° C.
Yield: 0.07 g (16% of theory)
R _f value: 0.2 (silica gel, methylene chloride / methanol / concentrated ammonia = 90: 10: 1)
Mp: 198-199 ° C

C ₂₄ H ₂₄ N ₆ O ₂ Mass spectrum: m / z = 429 [M + H] ⁺ ; m / z = 427 [MH] ^- ; m / z = 451 [M + Na] ⁺

Analogously to Example 2.0, the following compounds of the general formula I.2 are prepared from the starting materials indicated in each case:

Example 3.0

6-chloro-3- (Z) - [1- (4- {N- (dimethylaminomethylcarbonyl) -N-methyl-amino} -phenylamino) -1- (4-pyridyl) methylene] -2-indolinone

0.270 g of 1-acetyl-6-chloro-3- [1-chloro-1- (4-pyridyl) methylene] -2-indolinone (educt XIII.3), 0.232 g of N- (dimethylaminomethylcarbonyl) -N-methyl- p-phenylenediamine and 0.40 ml triethylamine are heated under reflux in 10 ml tetrahydrofuran for 15 hours. After cooling, 0.50 ml of piperidine are added and the mixture is stirred at room temperature for 2 hours. The residue obtained by distilling off the volatile constituents is purified chromatographically on a silica gel column using dichloromethane / methanol = 9: 1 as the eluent. The crude product thus obtained is stirred with methanol, suction filtered and dried at 80 ° C. Yield: 0.075 g (20% of theory)
R _f value: 0.3 (silica gel, dichloromethane / methanol = 9: 1)
Mp: 274-276 ° C
C ₂₅ H ₂₄ ClN ₅ O ₂ Mass spectrum: m / z = 462/464 [M + H] ⁺ ; m / z = 460/462 [MH] ^-

Analogously to Example 3.0, the following compounds of the general formula I.3 are prepared from the starting materials indicated in each case:

Example 4.0

6-chloro-3- (Z) - {1- [4- (pyrrolidin-1-ylmethyl) phenylamino] -1- (benzimidazol-5-yl) methylene} -2-indolinone

0.184 6-chloro-3- (1- (4- (pyrrolidin-1-ylmethyl) phenylamino) -1- (3,4-diaminophenyl) -methylene) -2-indolinone (educt XVIII.1), are in 5 ml Formic acid heated under reflux for 1 hour. The residue obtained by distilling off the solvent is suspended in water, made alkaline by adding sodium carbonate solution and extracted with ethyl acetate. The ethyl acetate phase is counter-extracted three times with water and dried over sodium sulfate. The residue obtained by distilling off the solvent is stirred with diethyl ether, suction filtered, washed with diethyl ether and dried at 80.degree.
Yield: 0.150 g (80% of theory)
R _f value: 0.5 (silica gel, methylene chloride / methanol / concentrated ammonia = 85: 15: 1.5)
Mp: 277-279 ° C C ₂₇ H ₂₄ CIN ₅ O Mass spectrum: m / z = 468/470 [MH] ^-

Analogously to Example 4.0, the following compounds of the general formula I.4 are prepared under the reaction conditions given in each case:

Example 5.0

3- (Z) - {1- [4- (dimethylaminomethyl) phenylamino] -1- (benzimidazol-5-yl) methylene} -2-indolinone

0.429 g of 3- (1- (4- (dimethylaminomethyl) phenylamino) -1- (4-amino-3-nitrophenyl) -methylene) -2-indolinone (educt XVII.6) are in 30 ml of formic acid with the addition of 0.50 g Raney nickel hydrogenated at room temperature for 3.5 hours under 50 psi hydrogen pressure. The catalyst is suctioned off, the solution is concentrated and the residue is dissolved in dichloromethane / methanol / ammonia = 50: 50: 1. The solution is filtered through silica gel, the residue obtained by distilling off the solvent is taken up in sodium carbonate solution and stirred overnight. The resulting precipitate is filtered off, washed with water, dried, with Di ethyl ether stirred, filtered off again and dried at 100 ° C.
Yield: 0.320 g (78% of theory)
R _f value: 0.4 (silica gel, methylene chloride / methanol / concentrated ammonia = 80: 20: 2)
Mp .: 273-277 ° C (decomposition) C ₂₅ H ₂₃ N ₅ O Mass spectrum: m / z = 408 [MH] ^-

Analogously to example 5.0, the following is done Connected:

(5.1) 6-Chloro-3- (Z) - [1- (4- {N-methanesulfonyl-N- (2-dimethylaminoethyl) amino} phenylamino) -1- (benzimidazol-5-yl) methylene ] -2-indolinone from 6-chloro-3- [1- (4- {N-methanesulfonyl-N- (2-dimethylaminoethyl) amino} phenylamino) -1- (4-amino-3- nitrophenyl) methylene] -2-indolinone.
R _f value: 0.5 (silica gel, methylene chloride / methanol / concentrated ammonia = 85: 15: 1.5)
Mp: 160 ° C (sintered) C ₂₇ H ₂₇ ClN ₆ O ₃ S Mass spectrum: m / z = 551/553 [M + H] ⁺ ; m / z = 549/551 [MH] ^-

Example 6.0

3- (Z) - [1- (1-methylpiperidin-4-ylamino) -1- (3-furyl) methylene] -2-indolinone

4.30 g of 1-acetyl-3- [1-hydroxy-1- (3-furyl) methylene] -2-indolinone (educt X.14) and 3.6 g of 4-amino-1-methylpiperidine are at 140 ° C. for 1.5 hours heated, after cooling, 2 N hydrochloric acid and ethyl acetate are added and the mixture is stirred until completely dissolved. The aqueous phase is separated off with conc. Ammonia solution made alkaline. The resulting precipitate is filtered off, washed with ice water, dried, stirred with acetone, suctioned off again and dried again.
Yield: 0.287 g (5.6% of theory)
R _f value: 0.5 (silica gel, dichloromethane / methanol / concentrated ammonia = 50: 10: 0.1)
Mp: 255-260 ° C C ₁₉ H ₂₁ N ₃ O ₂ Mass spectrum: m / z = 323 [M] ⁺

The following are analogous to example 6.0 Connections established:

(6.1) 3- (Z) - [1- (1-Methylpiperidin-4-ylamino) -1- (3-thienyl) methylene] -2-indolinone from 1-acetyl-3- (1-hydroxy-1- (3-thienyl) methylene-2-indolinone (educt X.2).

The product precipitates out as hydrochloride, which is washed and dried.
R _f value: 0.55 (silica gel, dichloromethane / methanol / concentrated ammonia = 50: 10: 0.1)
Mp .: 360 ° C C ₁₉ H ₂₁ N ₃ OS Mass spectrum: m / z = 339 [M] ⁺

(6.2) 3- (Z) - [1- (1-methylpiperidin-4-ylamino) -1- (4-imidazolyl) methylene] -2-indolinone from 1-acetyl-3- [1-hydroxy-1- (4-imidazolyl) -methylene] -2-indolinone (educt XI.3).
R _f value: 0.18 (silica gel, ethyl acetate / methanol / concentrated ammonia 5: 5: 1)
Mp: 274-279 ° C C ₁₈ H ₁₈ ClN ₃ O Mass spectrum: m / z = 324 [M + H] ⁺ ; m / z = 322 [MH] ^-

(6.3) 3- (Z) - [1- (1-Methylpiperidin-4-ylamino) -1- (2-furyl) methylene] -2-indolinone from 1-acetyl-3- [1-hydroxy-1- (2-furyl) methylene] -2-indolinone
R _f value: 0.45 (silica gel, dichloromethane / methanol / concentrated ammonia = 50: 10: 1)
Mp: 255-260 ° C C ₁₉ H ₂₁ N ₃ O ₂ Mass spectrum: m / z = 323 [M] ⁺

Example 7.0

6-chloro-3- (Z) - {1- [4- (dimethylaminomethyl) = phenylamino] -1- (1-methylbenzimidazol-5-yl) methylene} -2-indolinone

0.344 g of 6-chloro-3- [1-chloro-1- (1-methylbenzimidazol-5-yl) methylene] -2-indolinone (educt XIII.4), 0.195 g of 4- (dimethylaminomethyl) aniline and 0.513 ml Ethyldiisopropylamine are stirred in 5 ml DMF at 100 ° C for 6 hours. After further addition of 0.090 g of 4- (dimethylaminomethyl) aniline and 0.34 ml of ethyldiisopropylamine, the mixture is stirred at 100 ° C. for a further 6 hours. After cooling and adding water, the precipitate formed is suction filtered and washed with water. The crude product thus obtained is purified by chromatography on an Alox column with ethyl acetate / methanol = 95: 5 as the eluent. The product is stirred with ice-cold diethyl ether, suction filtered and dried at 80 ° C.
Yield: 0.060 g (13% of theory)
R _f value: 0.52 (Alox, ethyl acetate / methanol = 95: 5)
Mp .: 288 ° C (decomposition) C ₂₆ H ₂₄ ClN ₅ O Mass spectrum: m / z = 458/460 [M + H] ⁺

The following compounds of the general formula I.7 are prepared analogously to Example 7.0:

Example 8.0

6-chloro-3- (Z) - {1- [4- (ethylaminomethyl) -phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -2-indolinone

0.8 g of 1-acetyl-6-chloro-3- (Z) - {1- [4- (N-tert-butoxycarbonyl-N-ethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene } -2-indolinone (Example 1.17) are stirred in 7 ml of trifluoroacetic acid and 14 ml of dichloromethane for 1.5 hours at room temperature. The residue obtained after distilling off the volatile constituents is triturated with diethyl ether, the precipitate obtained is filtered off with suction and dried at 100.degree.
Yield: 0.78 g (95% of theory)
R _f value: 0.42 (silica gel, dichloromethane / methanol / concentrated ammonia = 90: 10: 1)
Mp: 248-250 ° C C ₂₅ H ₂₂ ClN ₃ O ₃ .C ₂ HF ₃ O ₂ Mass spectrum: m / z = 470/472 [M + Na] ⁺

The following compounds of the general formula I.8 are prepared analogously to Example 8.0:

Example 9.0

6-carboxy-3- (Z) - {1- [4- (1-methylpiperazin-4-yl-methyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -2-indolinone

0.36 g of 6-methoxycarbonyl-3- (Z) - {1- [4- (1-methylpiperazin-4-ylmethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -2-indolinone ( Example 1.57) in 5 ml of ethanol are mixed at 80 ° C with 1.6 ml of 1 molar sodium hydroxide solution and stirred at 80 ° C for 2 hours. After adding 1.6 ml of 1 molar hydrochloric acid and 2 ml of water, the mixture is stirred overnight without heating. The resulting precipitate is filtered off, washed successively with water, a little ethanol and finally with diethyl ether and then dried at 80 ° C.
Yield: 0.32 g (91% of theory)
R _f value: 0.15 (silica gel, dichloromethane / methanol = 4: 1) C ₃₀ H ₃₀ N ₄ O ₅ Mass spectrum: m / z = 527 [M + H] ⁺ ; m / z = 525 [MH] ^-

Example 10.0

6-methylaminocarbonyl-3- (Z) - {1- [4- (1-methylpiperazin-4-yl-methyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -2-indolinone

0.100 g of 6-carboxy-3- (Z) - {1- [4- (1-methylpiperazin-4-ylmethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -2-indolinone, 0.103 g of dimethylamine hydrochloride, 73 mg of TBTU, 35 mg of HOBT and 0.416 ml of triethylamine are stirred in 3 ml of DMF for 6 hours at room temperature. The reaction mixture is poured onto water and extracted three times with dichloromethane / methanol 19: 1. The combined organic phases are washed with water and dried over sodium sulfate. Undissolved constituents are filtered off and the filtrate is evaporated to dryness in vacuo. The residue is triturated with diethyl ether, suction filtered and dried at 80 ° C.
Yield: 0.075 g (73% of theory)
R _f value: 0.38 (silica gel, dichloromethane / methanol = 9: 1)
Mp: 172 ° C C ₃₁ H ₃₃ N ₅ O ₄ Mass spectrum: m / z = 540 [M + H] ⁺ ; m / z = 538 [MH] ^-

Analogously to example 10.0, the following becomes Connected:

(10.1) 6-Dimethylaminocarbonyl-3- (Z) - {1- [4- (1-methylpiperazin-4-ylmethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -2-indolinone under Use of dimethylamine hydrochloride.
R _f value: 0.51 (silica gel, dichloromethane / methanol = 9: 1)
Mp: 257 ° C C ₃₂ H ₃₅ N ₅ O ₄ Mass spectrum: m / z = 554 [M + H] ⁺ ; m / z = 552 [MH] ^-

Example 11

6-fluoro-3- (Z) - {1- [4- (ethylaminomethyl) -phenylamino] -1- (1-methylbenzimidazol-5-yl) methylene} -2-indolinone

A solution of 0.30 g of 1-acetyl-6-fluoro-3- [1-methoxy-1- (1-methylbenzimidazol-5-yl) methylene] -2-indolinone (Example XIX) and 0.206 g of 4- (N-ethyl-N-tert-butoxycarbonylaminomethyl) aniline (Example XXV.12) in 5 ml DMF is stirred at 115 ° C for 15 hours. The by distilling off of the solvent residue obtained is taken up in 5 ml of methanol and after the addition of 1 ml of 1 M sodium hydroxide solution Stirred for 1 hour. The solution is neutralized by adding ammonium chloride solution and then to Evaporated to dryness. The residue is chromatographically over a silica gel column cleaned with dichloromethane / methanol / ammonia = 90: 10: 1. That so intermediate obtained is dissolved in 5 ml of dichloromethane, with 1 ml trifluoroacetic acid added and stirred for 30 minutes. To

The volatile constituents are distilled off and the residue is crystallized from diethyl ether and then dried at 80.degree.
Yield: 0.143 g (31% of theory)
R _f value: 0.2 (silica gel, dichloromethane / methanol / concentrated ammonia solution = 80: 20: 1)
Mp: 226-228 ° C C ₂₆ H ₂₄ FN ₅ O.C ₂ HF ₃ O ₂

Beispiel 13 Trockenampulle mit 75 mg Wirkstoff pro 10 ml Zusammensetzung: Wirkstoff 75.0 mg Mannitol 50.0 mg Wasser für Injektionszwecke ad 10.0 ml The following compounds of the general formula I.11 are prepared analogously to Example 11.0:

Example 13 Dry ampoule with 75 mg of active ingredient per 10 ml of composition: active substance 75.0 mg mannitol 50.0 mg Water for injections ad 10.0 ml

production:

Active ingredient and mannitol are dissolved in water. After filling, freeze-drying. The ready-to-use solution is dissolved with water for injections. Example 14 Dry ampoule with 35 mg of active ingredient per 2 ml of composition: active substance 35.0 mg mannitol 100.0 mg Water for injections ad 2.0 ml

production:

Active ingredient and mannitol are in Water dissolved. After bottling is freeze-dried.

The ready-to-use solution is dissolved with water for injections. Example 15 Tablet with 50 mg of Active Ingredient Composition: (1) Active ingredient 50.0 mg (2) milk sugar 98.0 mg (3) corn starch 50.0 mg (4) polyvinyl pyrrolidone 15.0 mg (5) Magnesium stearate 2.0 mg 215.0 mg

production:

(1), (2) and (3) are mixed and granulated with an aqueous solution of (4). (5) is added to the dried granulate. Tablets are pressed from this mixture, biplan with facets on both sides and partial notch on one side. Tablet diameter: 9 mm. Example 16 Tablet with 350 mg of Active Ingredient Composition: (1) Active ingredient 350.0 mg (2) milk sugar 136.0 mg (3) corn starch 80.0 mg (4) polyvinyl pyrrolidone 30.0 mg (5) Magnesium stearate 4.0 mg 600.0 mg

production:

(1), (2) and (3) are mixed and granulated with an aqueous solution of (4). (5) is added to the dried granulate. Tablets are pressed from this mixture, biplan with facets on both sides and partial notch on one side. Tablet diameter: 12 mm. Example 17 Capsules with 50 mg of Active Ingredient Composition: (1) Active ingredient 50.0 mg (2) Dried corn starch 58.0 mg (3) powdered milk sugar 50.0 mg (4) Magnesium stearate 2.0 mg 160.0 mg

production:

(1) is triturated with (3). This The mixture of (2) and (4) is triturated with intensive mixing added.

This powder mixture is filled into size 3 hard gelatin capsules on a capsule filling machine. Example 18 Capsules with 350 mg of Active Ingredient Composition: (1) Active ingredient 350.0 mg (2) Dried corn starch 46.0 mg (3) powdered milk sugar 30.0 mg (4) Magnesium stearate 4.0 mg 430.0 mg

production:

(1) is triturated with (3). This The mixture of (2) and (4) is triturated with intensive mixing added.

This powder mixture is on a Capsule filling machine in hard gelatin capsules Bottled size 0.

Example 19

Suppositories with 100 mg of active ingredient

1 suppository contains: active substance 100.0 mg Polyethylene glycol (MG 1500) 600.0 mg Polyethylene glycol (MG 6000) 460.0 mg polyethylene sorbitan monostearate 840 mg 2,000.0 mg

production:

The polyethylene glycol is put together melted with polyethylene sorbitan monostearate. At 40 ° C milled active substance dispersed homogeneously in the melt. It will to 38 ° C chilled and in slightly pre-chilled Poured out suppository molds.

• (1) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (2) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (3) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (4) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)methylen}-6-cyano-2-indolinon
• (5) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (6) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (7) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (8) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (9) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (10) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (11) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylarino]-1-(3,4-methylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (12) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (13) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (14) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (15) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (16) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (17) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (18) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (19) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (20) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1- (3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (21) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (22) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (23) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (24) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (25) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (26) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-cyano-2-indolinon
• (27) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (28) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (29) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (30) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (31) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (32) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (33) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (34) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (35) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(3,4-methylendinxyphenyl)-methylen}-6-nitro-2-indolinon
• (36) 3-(Z)-{1-[4-(N-Methansultonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (37) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylarnino]-1-(3,4-methylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (38) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (39) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (40) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (41) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (42) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (43) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (44) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (45) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (46) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (47) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (48) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (49) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• s(50) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylarnino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (51) 3-(Z)-{1-[4-(N-Methyi-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (52) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-nitro-2-indolinon
• (53) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (54) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (55) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (56) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (57) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (58) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (59) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (60) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (61) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (62) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (63) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (64) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (65) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (66) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (67) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (68) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (69) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (70) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (71) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (72) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (73) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (74) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (75) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (76) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (77) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolincin
• (78) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (79) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (80) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(3,4-methylendioxy- phenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (81) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl}-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (82) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (83) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (84) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (85) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (86) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (87) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2- indolinon
• (88) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (89) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (90) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (91) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (92) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (93) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (94) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (95) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (96) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (97) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (98) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (99) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (100) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (101) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (102) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (103) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (104) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-ethoxycarbonyl-2-indolinon
• (105) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (106) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (107) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (108) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (109) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (110) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (111) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (112) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (113) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (114) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (115) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (116) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (117) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (118) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (119) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (120) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (121) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (122) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (123) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (124) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (125) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (126) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (127) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (128) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (129) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (130) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-fluor-2-indolinon
• (131) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (132) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (133) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (134) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (135) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (136) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (137) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (138) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (139) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (140) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (141) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (142) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (143) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (144) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (145) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1- (benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (146) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (147) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (148) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (149) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (150) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (151) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (152) 3-(Z)-{1-[4-(Dimethyiaminomethyn-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (153) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (154) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (155) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (156) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (157) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (158) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (159) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (160) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)- phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (161) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (162) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (163) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (164) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-fluor-2-indolinon
• (165) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• (166) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• (167) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• (168) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• s(169) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• (170) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• (171) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• (172) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• (173) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• (174) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• (175) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1- (benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• (176) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• (177) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(benzo[1,4]dioxin-6-yl)-methylen}-6-chlor-2-indolinon
• (178) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3-methyl-benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (179) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(3-methyl-benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (180) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(3-methylbenzoxazol-2-on-6-yl)-methyleh}-6-chlor-2-indolinon
• (181) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(3-methyl-benzoxazol-2-on-fi-yn-methylen}-6-chlor-2-indolinon
• (182) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3-methyl-benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (183) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(3-methyl-benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (184) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3-methyl-benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (184) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(3-methyl-benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (185) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(3-methyl-benzoxazol-2-on-6-)-methylen}-6-chlor-2-indolinon
• (186) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3-methyl-benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (187) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(3-methyl-benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (188) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(3-methyl-benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (189) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(3-methyl-benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (190) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (191) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (192) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (193) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (194) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (195) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylameno]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-endolinon
• (196) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino phenylamino]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (197) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (198) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• s(199) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (200) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (201) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (202) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(benzoxazol-2-on-6-yl)-methylen}-6-chlor-2-indolinon
• (203) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(benzoxazol-2-on-5-yl)-methylen}-6-chlor-2-indolinon
• (204) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(benzoxazol-2-on-5-yl)-methylen}-6-chlor-2-indolinon
• (205) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(benzoxazol-2-on-5-yl)-methylen}-6-chlor-2-indolinon
• (206) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(benzoxazol-2-on-5-yl)-methylen}-6-chlor-2-indolinon
• (207) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(benzoxazol-2-on-5-yl)-methylen}-6-chlor-2-indolinon
• (208) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(benzoxazol-2-on-5-yl)-methylen}-6-chlor-2-indolinon
• (209) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(benzoxazol-2-on-5-y1)-methylen}-6-chlor-2-indolinon
• (210) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(benzoxazol-2-on-5-yl)-methylen}-6-chlor-2-indolinon
• (211) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(benzoxazol-2-on-5-yl)-methylen}-6-chlor-2-indolinon
• (212) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(benzoxazol-2-on-5-yl)-methylen}-6-chlor-2-indolinon
• (213) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(benzoxazoI-2-on-5-yl)-methylen}-6-chlor-2-indolinon
• (214) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(benzoxazol-2-on-5-yl)-methylen}-6-chlor-2-indolinon
• (215) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(benzoxazol-2-on-5-yl)-methylen}-6-chlor-2-indolinon
• (216) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(chinolin-7-yl)-methylen}-6-chlor-2-indolinon
• (217) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(chinolin-7-yl)-methylen}-6-chlor-2-indolinon
• (218) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(chinolin-7-yl)-methylen}-6-chlor-2-indolinon
• (219) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(chinolin-7-yl)-methylen}-6-chlor-2-indolinon
• (220) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(chinolin-7-y1)-methylen}-6-chlor-2-indolinon
• (221) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(chinolin-7-yl)-methylen}-6-chlor-2-indolinon
• (222) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(chinolin-7-ylrmethylen}-6-chlor-2-indolinon
• (223) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(chinolin-7-yl)-methylen}-6-chlor-2-indolinon
• (224) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(chinolin-7-yl)-methylen}-6-chlor-2-indolinon
• (225) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenyl amino]-1-(chinolin-7-yl)-methylen}-6-chlor-2-indolinon
• (226) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(chinolin-7-yl)-methylen}-6-chlor-2-indolinon
• (227) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(chinolin-7-yl)-methylen}-6-chlor-2-indolinon
• s(228) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(chinolin-7-yl)-methylen}-6-chlor-2-indolinon
• (229) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• (230) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• (231) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• (232) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• (233) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• (234) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• (235) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• (236) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• (237) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• (238) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• (239) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• (240) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• (241) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(chinolin-6-yl)-methylen}-6-chlor-2-indolinon
• s(242) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (243) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (244) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (245) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (246) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (247) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (248) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1- (benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (249) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (250) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (251) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (252) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (253) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (254) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(benzothiazol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (255) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenyiamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (256) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• s(257) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (258) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (259) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (260) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (261) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (262) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (263) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (264) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (265) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (266) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (267) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(benzothiazol-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (268) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (269) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-ir2dolinon
• (270) 3-(Z)-{1-[4-(1-Meihylpiperazin-4-yl-methyl)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (271) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (272) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (273) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (274) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (275) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (276) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (277) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (278) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (279) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (280) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-y1)-phenylamino]-1-(indol-5-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (281) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (282) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (283) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (284) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indalinon
• (285) 3-(Z)-{1-[4-(N-Methyi-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (286) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (287) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (288) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (289) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (290) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (291) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (292) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (293) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(phthalazin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (294) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methylen}-6-chlor-2-indolinon
• (295) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methylen}-6-chlor-2-indolinon
• (296) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methylen}-6-chlor-2-indolinon
• (297) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methylen}-6-chlor-2-indolinon
• (298) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methylen}-6-chlor-2-indolinon
• (299) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methylen}-6-chlor-2-indolinon
• (300) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-y1)-methylen}-6-chlor-2-indolinon
• (301) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methylen}-6-chlor-2-indolinon
• (302) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(4-methyl-3,4-dihyd ro-2H-benzo[1,4]oxazin-7-yl)-methylen}-6-chlor-2-indolinon
• (303) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(4-methyl-3,4-dihydro-2N-benzo[1,4]oxazin-7-yl)-methylen}-6-chlor-2-indolinon
• (304) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methylen}-6-chlor-2-indolinon
• (305) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(4-methyl-3,4-dihydro-2N-benzo[1,4]oxazin-7-yl)-methylen}-6- chlor-2-indolinon
• (306) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino}-1-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-7-yl)-methylen}-6-chlor-2-indolinon
• (307) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (308) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (309) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (310) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (311) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (312) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (313) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (314) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (315) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (316) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (317) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (318) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (319) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(4-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (320) 3-(Z)-{1-[4-(Dimethylaminomethyl)-phenylamino]-1-(3-pyridyl)-methylen}-6- methoxycarbonyl-2-indolinon
• (321) 3-(Z)-{1-[4-(Diethylaminomethyl)-phenylamino]-1-(3-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (322) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-methyl)-phenylamino]-1-(3-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (323) 3-(Z)-{1-[4-(Ethylaminomethyl)-phenylamino]-1-(3-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (324) 3-(Z)-{1-[4-(N-Methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• s(325) 3-(Z)-{1-[4-(N-Methyl-N-{1-methylpiperazin-4-yl-methylcarbonyl}-amino)-phenylamino]-1-(3-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (326) 3-(Z)-{1-[4-(N-Acetyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (327) 3-(Z)-{1-[4-(N-Acetyl-N-{3-dimethylamino-propyl}-amino)-phenylamino]-1-(3-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (328) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl}-aminocarbonyl)-phenylamino]-1-(3-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (329) 3-(Z)-{1-[4-(N-Methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (330) 3-(Z)-{1-[4-(1-Methylpiperazin-4-yl-carbonylmethyl)-phenylamino]-1-(3-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (331) 3-(Z)-{1-[4-(N-Methyl-N-{2-dimethylamino-ethyl-carbonyl}-amino)-phenylamino]-1-(3-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (332) 3-(Z)-{1-[4-(1-Methyl-imidazol-2-yl)-phenylamino]-1-(3-pyridyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (333) 3-(Z)-{1-[3-Fluor-4-(N-methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (334) 3-(Z)-{1-[3-Fluor-4-(N-methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (335) 3-(Z)-{1-[3-Fluor-4-(N-methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (336) 3-(Z)-{1-[3-Fluor-4-(N-methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (337) 3-(Z)-{1-[3-Fluor-4-(N-methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(2-thienyl)-methylen}-6-chlor-2-indolinon
• (338) 3-(Z)-{1-[3-Fluor-4-(N-methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (339) 3-(Z)-{1-[3-Fluor-4-(N-methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3-thienyl)-methylen}-6-chlor-2-indolinon
• (340) 3-(Z)-{1-[3-Fluor-4-(N-methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (341) 3-(Z)-{1-[3-Fluor-4-(N-methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (342) 3-(Z)-{1-[3-Fluor-4-(N-methyl-N-{dimethylaminomethyl-carbonyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (343) 3-(Z)-{1-[3-Fluor-4-(N-methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (344) 3-(Z)-{1-[3-Fluor-4-(N-methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-methylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (345) 3-(Z)-{1-[3-Fluor-4-(N-methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (346) 3-(Z)-{1-[3-Fluor-4-(N-methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (347) 3-(Z)-{1-[3-Fluor-4-(N-methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(2-thienyl)-methylen}-6-chlor-2-indolinon
• (348) 3-(Z)-{1-[3-Fluor-4-(N-methansulfonyl-N-{2-dimethylamino-ethyl}-amino)- phenylamino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (349) 3-(Z)-{1-[3-Fluor-4-(N-methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3-thienyl)-methylen}-6-chlor-2-indolinon
• (350) 3-(Z)-{1-[3-Fluor-4-(N-methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (351) 3-(Z)-{1-[3-Fluor-4-(N-methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (352) 3-(Z)-{1-[3-Fluor-4-(N-methansulfonyl-N-{2-dimethylamino-ethyl}-amino)-phenylamino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon
• (353) 3-(Z)-{1-[1-Methyl-2-(N-{2-dimethylamino-ethyl}-N-methyl-aminocarbonyl)-pyrrol-4-yl-amino]-1-(3,4-methylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (354) 3-(Z)-{1-[1-Methyl-2-(N-{2-dimethylamino-ethyl}-N-methyl-aminocarbonyl)-pyrrol-4-y1-amino]-1-(3,4-methylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (355) 3-(Z)-{1-[1-Methyl-2-(N-{2-dimethylamino-ethyl}-N-methyl-aminocarbonyl)-pyrrol-4-yl-amino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-chlor-2-indolinon
• (356) 3-(Z)-{1-[1-Methyl-2-(N-{2-dimethylamino-ethyl}-N-methyl-aminocarbonyl)-pyrrol-4-yl-amino]-1-(3,4-ethylendioxyphenyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (357) 3-(Z)-{1-[1-Methyl-2-(N-{2-dimethylamino-ethyl}-N-methyl-aminocarbonyl)-pyrrol-4-yl-amino]-1-(2-thienyl)-methylen}-6-chlor-2-indolinon
• (358) 3-(Z)-{1-[1-Methyl-2-(N-{2-dimethylamino-ethyl}-N-methyl-aminocarbonyl)-pyrrol-4-yl-amino]-1-(2-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (359) 3-(Z)-{1-[1-Methyl-2-(N-{2-dimethylamino-ethyl}-N-methyl-aminocarbonyl)-pyrrol-4-yl-amino]-1-(3-thienyl)-methylen}-6-chlor-2-indolinon
• (360) 3-(Z)-{1-[1-Methyl-2-(N-{2-dimethylamino-ethyl}-N-methyl-aminocarbonyl)-pyrrol-4-yl-amino]-1-(3-thienyl)-methylen}-6-methoxycarbonyl-2-indolinon
• (361) 3-(Z)-{1-[1-Methyl-2-(N-{2-dimethylamino-ethyl}-N-methyl-aminocarbonyl)-pyrrol-4-yl-amino]-1-(chinoxalin-6-yl)-methylen}-6-chlor-2-indolinon
• (362) 3-(Z)-{1-[1-Methyl-2-(N-{2-dimethylamino-ethyl}-N-methyl-aminocarbonyl)-pyrrol-4-yl-amino]-1-(chinoxalin-6-yl)-methylen}-6-methoxycarbonyl-2-indolinon

The following compounds can be prepared analogously to the examples above:

• (1) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (2) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (3) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (4) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (5) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-cyano -2-indolinone
• (6) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) - methylene} -6-cyano-2-indolinone
• (7) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6 cyano-2-indolinone
• (8) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6 cyano-2-indolinone
• (9) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6 cyano-2-indolinone
• (10) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-methylenedioxyphen yl) methylene} -6-cyano-2-indolinone
• (11) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylarino] -1- (3,4-methylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (12) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (13) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (14) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (15) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (16) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (17) 3- (Z) - {1- [4- (Ethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (18) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-cyano -2-indolinone
• (19) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) - methylene} -6-cyano-2-indolinone
• (20) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6 cyano-2-indolinone
• (21) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6 cyano-2-indolinone
• (22) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6 cyano-2-indolinone
• (23) 3- (Z) - {1- [4- (N-Methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6 cyano-2-indolinone
• (24) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (25) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (26) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-cyano-2-indolinone
• (27) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (28) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (29) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (30) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (31) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethyl-carbonyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-nitro -2-indolinone
• (32) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) - methylene} -6-nitro-2-indolinone
• (33) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6 -nitro-2-indolinone
• (34) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6 -nitro-2-indolinone
• (35) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (3,4-methylenedinoxyphenyl) methylene} -6 -nitro-2-indolinone
• (36) 3- (Z) - {1- [4- (N-methanesultonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6 -nitro-2-indolinone
• (37) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylarnino] -1- (3,4-methylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (38) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (39) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (40) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (41) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (42) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (43) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (44) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-nitro -2-indolinone
• (45) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) - methylene} -6-nitro-2-indolinone
• (46) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6 -nitro-2-indolinone
• (47) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6 -nitro-2-indolinone
• (48) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6 -nitro-2-indolinone
• (49) 3- (Z) - {1- [4- (N-Methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6 -nitro-2-indolinone
• s (50) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylarnino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-nitro-2- indolinone
• (51) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (52) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-nitro-2-indolinone
• (53) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (2-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (54) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (2-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (55) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (2-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (56) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (2-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (57) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (2-thienyl) methylene} -6-methoxycarbonyl-2 -indolinon
• (58) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (2-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (59) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (2-thienyl) methylene} -6-methoxycarbonyl -2-indolinone
• (60) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylaminopropyl} amino) phenylamino] -1- (2-thienyl) methylene} -6-methoxycarbonyl -2-indolinone
• (61) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (2-thienyl) methylene} -6- methoxycarbonyl-2-indolinone
• (62) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (2-thienyl) methylene} -6-methoxycarbonyl -2-indolinone
• (63) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (2-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (64) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (2-thienyl) methylene} -6 methoxycarbonyl-2-indolinone
• (65) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (2-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (66) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (67) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (68) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (69) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (70) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl-2 -indolinon
• (71) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (72) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl -2-indolinone
• (73) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl -2-indolinone
• (74) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl -2-indolinone
• (75) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl -2-indolinone
• (76) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (77) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (3-thienyl) methylene} -6 methoxycarbonyl-2-indolincin
• (78) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (79) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (80) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (81) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl} phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (82) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (83) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-ethoxycarbonyl -2-indolinone
• (84) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) - methylene} -6-ethoxycarbonyl-2-indolinone
• (85) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6 ethoxycarbonyl-2-indolinone
• (86) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) meth ylene} -6-ethoxycarbonyl-2-indolinone
• (87) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6 -ethoxycarbonyl-2-indolinone
• (88) 3- (Z) - {1- [4- (N-Methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6 ethoxycarbonyl-2-indolinone
• (89) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (90) 3- (Z) - {1- [4- (N-methyl-N- {2-dimethylamino-ethyl-carbonyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (91) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (92) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (93) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (94) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (95) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (96) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-ethoxycarbonyl -2-indolinone
• (97) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) - methylene} -6-ethoxycarbonyl-2-indolinone
• (98) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6 ethoxycarbonyl-2-indolinone
• (99) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6 ethoxycarbonyl-2-indolinone
• (100) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6 ethoxycarbonyl-2-indolinone
• (101) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6 ethoxycarbonyl-2-indolinone
• (102) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (103) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (104) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-ethoxycarbonyl-2-indolinone
• (105) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (106) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (107) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (108) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (109) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-methoxycarbonyl -2-indolinone
• (110) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (quinoxalin-6-yl) - methylene} -6-methoxycarbonyl-2-indolinone
• (111) 3- (Z) - {1- [4- (N-acetyl-N- {2-dimethylamino-ethyl} amino) phenylamino] -1- (quinoxalin-6-yl) -methylene} -6 methoxycarbonyl-2-indolinone
• (112) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (quinoxalin-6-yl) -methylene} -6 methoxycarbonyl-2-indolinone
• (113) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (114) 3- (Z) - {1- [4- (N-Methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (quinoxalin-6-yl) -methylene} -6 methoxycarbonyl-2-indolinone
• (115) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (116) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylamino-ethyl-carbonyl} -amino) -phenylamino] -1- (quinoxalin-6-yl) -methylene} -6-methoxycarbonyl-2-indolinone
• (117) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (118) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-fluoro-2-indolinone
• (119) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (quinoxalin-6-yl) -methylene} -6-fluoro-2-indolinone
• (120) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-fluoro-2-indolinone
• (121) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (quinoxalin-6-yl) -methylene} -6-fluoro-2-indolinone
• (122) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-fluorine -2-indolinone
• (123) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (quinoxalin-6-yl) - methylene} -6-fluoro-2-indolinone
• (124) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (quinoxalin-6-yl) methylene} -6 fluoro-2-indolinone
• (125) 3- (Z) - {1- [4- (N-acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (quinoxalin-6-yl) -methylene} -6 fluoro-2-indolinone
• (126) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6 fluoro-2-indolinone
• (127) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylamino-ethyl} amino) phenylamino] -1- (quinoxalin-6-yl) -methylene} -6 fluoro-2-indolinone
• (128) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-fluoro-2-indolinone
• (129) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylamino-ethyl-carbonyl} -amino) -phenylamino] -1- (quinoxalin-6-yl) -methylene} -6-fluoro-2-indolinone
• (130) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-fluoro-2-indolinone
• (131) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-chloro-2-indolinone
• (132) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-chloro-2-indolinone
• (133) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-chloro-2-indolinone
• (134) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-chlorine -2-indolinone
• (135) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (quinoxalin-6-yl) -methylene} -6 chloro-2-indolinone
• (136) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6 chloro-2-indolinone
• (137) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-chloro-2-indolinone
• (138) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylamino-ethyl-carbonyl} -amino) -phenylamino] -1- (quinoxalin-6-yl) -methylene} -6-chloro-2-indolinone
• (139) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (140) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (141) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (142) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (143) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6-yl) - methylene} -6-methoxycarbonyl-2-indolinone
• (144) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (benzo [1,4] dioxin -6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (145) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6-yl ) -methylene} -6-methoxycarbonyl-2-indolinone
• (146) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylaminopropyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6-yl ) -methylene} -6-methoxycarbonyl-2-indolinone
• (147) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl ) -methylene} -6-methoxycarbonyl-2-indolinone
• (148) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6-yl ) -methylene} -6-methoxycarbonyl-2-indolinone
• (149) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (150) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6 -yl) -methylene} -6-methoxycarbonyl-2-indolinone
• (151) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (152) 3- (Z) - {1- [4- (Dimethyaminomethynphenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6-fluoro-2-indolinone
• (153) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6-fluoro-2-indolinone
• (154) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6 fluoro-2-indolinone
• (155) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6-fluoro-2-indolinone
• (156) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6-yl) - methylene} -6-fluoro-2-indolinone
• (157) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (benzo [1,4] dioxin -6-yl) methylene} -6-fluoro-2-indolinone
• (158) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6-yl ) -methylene} -6-fluoro-2-indolinone
• (159) 3- (Z) - {1- [4- (N-acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6-yl ) -methylene} -6-fluoro-2-indolinone
• (160) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl ) -methylene} -6-fluoro-2-indolinone
• (161) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6-yl ) -methylene} -6-fluoro-2-indolinone
• (162) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6 fluoro-2-indolinone
• (163) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6 -yl) -methylene} -6-fluoro-2-indolinone
• (164) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6 fluoro-2-indolinone
• (165) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6-chloro-2-indolinone
• (166) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6-chloro-2-indolinone
• (167) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6 chloro-2-indolinone
• (168) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6-chloro-2-indolinone
• s (169) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6-yl) -methylene} -6-chloro-2-indolinone
• (170) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (benzo [1,4] dioxin -6-yl) methylene} -6-chloro-2-indolinone
• (171) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6-yl ) -methylene} -6-chloro-2-indolinone
• (172) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6-yl ) -methylene} -6-chloro-2-indolinone
• (173) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl ) -methylene} -6-chloro-2-indolinone
• (174) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6-yl ) -methylene} -6-chloro-2-indolinone
• (175) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6 chloro-2-indolinone
• (176) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (benzo [1,4] dioxin-6 -yl) -methylene} -6-chloro-2-indolinone
• (177) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (benzo [1,4] dioxin-6-yl) methylene} -6 chloro-2-indolinone
• (178) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3-methyl-benzoxazol-2-one-6-yl) -methylene} -6-chloro-2-indolinone
• (179) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (3-methyl-benzoxazol-2-one-6-yl) -methylene} -6-chloro-2-indolinone
• (180) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (3-methylbenzoxazol-2-one-6-yl) methylh} -6 chloro-2-indolinone
• (181) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (3-methyl-benzoxazol-2-one-fi-yn-methylene} -6-chloro-2-indolinone
• (182) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3-methyl-benzoxazol-2-one-6-yl ) -methylene} -6-chloro-2-indolinone
• (183) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (3-methyl-benzoxazole-2 -on-6-yl) -methylene} -6-chloro-2-indolinone
• (184) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylamino-ethyl} amino) phenylamino] -1- (3-methyl-benzoxazol-2-one-6 -yl) -methylene} -6-chloro-2-indolinone
• (184) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (3-methyl-benzoxazol-2-one-6 -yl) -methylene} -6-chloro-2-indolinone
• (185) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (3-methyl-benzoxazol-2-one-6 -) - methylene} -6-chloro-2-indolinone
• (186) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3-methyl-benzoxazol-2-one-6 -yl) -methylene} -6-chloro-2-indolinone
• (187) 3- (Z) - {1- [4- (1-Methylpiperazin-4-yl-carbonylmethyl) phenylamino] -1- (3-methyl-benzoxazol-2-one-6-yl) meth ylene} -6-chloro-2-indolinone
• (188) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (3-methyl-benzoxazol-2-one -6-yl) methylene} -6-chloro-2-indolinone
• (189) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (3-methyl-benzoxazol-2-one-6-yl) methylene} -6-chloro-2-indolinone
• (190) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (benzoxazol-2-one-6-yl) methylene} -6-chloro-2-indolinone
• (191) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (benzoxazol-2-one-6-yl) -methylene} -6-chloro-2-indolinone
• (192) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (benzoxazol-2-one-6-yl) methylene} -6-chloro -2-indolinone
• (193) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (benzoxazol-2-one-6-yl) -methylene} -6-chloro-2-indolinone
• (194) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (benzoxazol-2-one-6-yl) methylene} -6-chloro-2-indolinone
• (195) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylameno] -1- (benzoxazol-2-one-6 -yl) -methylene} -6-chloro-2-endolinon
• (196) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino phenylamino] -1- (benzoxazol-2-one-6-yl) methylene} -6-chloro-2-indolinone
• (197) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} -amino) -phenylamino] -1- (benzoxazol-2-one-6-yl) - methylene} -6-chloro-2-indolinone
• (198) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (benzoxazol-2-one-6-yl) - methylene} -6-chloro-2-indolinone
• s (199) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (benzoxazol-2-one-6-yl) -methylene} -6-chloro-2-indolinone
• (200) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (benzoxazol-2-one-6-yl) methylene} -6-chloro -2-indolinone
• (201) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (benzoxazol-2-one-6-yl ) -methylene} -6-chloro-2-indolinone
• (202) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (benzoxazol-2-one-6-yl) methylene} -6-chloro -2-indolinone
• (203) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (benzoxazol-2-one-5-yl) -methylene} -6-chloro-2-indolinone
• (204) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (benzoxazol-2-one-5-yl) -methylene} -6-chloro-2-indolinone
• (205) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (benzoxazol-2-one-5-yl) methylene} -6-chloro -2-indolinone
• (206) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (benzoxazol-2-one-5-yl) -methylene} -6-chloro-2-indolinone
• (207) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (benzoxazol-2-one-5-yl) methylene} -6-chloro-2-indolinone
• (208) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (benzoxazol-2-one-5 -yl) -methylene} -6-chloro-2-indolinone
• (209) 3- (Z) - {1- [4- (N-acetyl-N- {2-dimethylamino-ethyl} amino) phenylamino] -1- (benzoxazol-2-one-5-y1) - methylene} -6-chloro-2-indolinone
• (210) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} -amino) -phenylamino] -1- (benzoxazol-2-one-5-yl) - methylene} -6-chloro-2-indolinone
• (211) 3- (Z) - {1- [4- (N-methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (benzoxazol-2-one-5-yl) - methylene} -6-chloro-2-indolinone
• (212) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (benzoxazol-2-one-5-yl) - methylene} -6-chloro-2-indolinone
• (213) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (benzoxazoI-2-one-5-yl) methylene} -6-chloro -2-indolinone
• (214) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (benzoxazol-2-one-5-yl ) -methylene} -6-chloro-2-indolinone
• (215) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (benzoxazol-2-one-5-yl) methylene} -6-chloro -2-indolinone
• (216) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (quinolin-7-yl) methylene} -6-chloro-2-indolinone
• (217) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (quinolin-7-yl) methylene} -6-chloro-2-indolinone
• (218) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (quinolin-7-yl) methylene} -6-chloro-2-indolinone
• (219) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (quinolin-7-yl) methylene} -6-chloro-2-indolinone
• (220) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (quinolin-7-y1) methylene} -6-chlorine -2-indolinone
• (221) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (quinolin-7-yl) - methylene} -6-chloro-2-indolinone
• (222) 3- (Z) - {1- [4- (N-acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (quinolin-7-ylrmethylene} -6-chloro 2-indolinone
• (223) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (quinolin-7-yl) -methylene} -6 chloro-2-indolinone
• (224) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (quinolin-7-yl) methylene} -6 chloro-2-indolinone
• (225) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (quinolin-7-yl) methylene} - 6-chloro-2-indolinone
• (226) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (quinolin-7-yl) methylene} -6-chloro-2-indolinone
• (227) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylamino-ethyl-carbonyl} -amino) -phenylamino] -1- (quinolin-7-yl) -methylene} -6-chloro-2-indolinone
• s (228) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (quinolin-7-yl) methylene} -6-chloro-2- indolinone
• (229) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (quinolin-6-yl) methylene} -6-chloro-2-indolinone
• (230) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (quinolin-6-yl) methylene} -6-chloro-2-indolinone
• (231) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (quinolin-6-yl) methylene} -6-chloro-2-indolinone
• (232) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (quinolin-6-yl) methylene} -6-chloro-2-indolinone
• (233) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (quinolin-6-yl) methylene} -6-chloro -2-indolinone
• (234) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (quinolin-6-yl) - methylene} -6-chloro-2-indolinone
• (235) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (quinolin-6-yl) methylene} -6 chloro-2-indolinone
• (236) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (quinolin-6-yl) -methylene} -6 chloro-2-indolinone
• (237) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (quinolin-6-yl) methylene} -6 chloro-2-indolinone
• (238) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (quinolin-6-yl) methylene} -6 chloro-2-indolinone
• (239) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (quinolin-6-yl) methylene} -6-chloro-2-indolinone
• (240) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylamino-ethyl-carbonyl} -amino) -phenylamino] -1- (quinolin-6-yl) -methylene} -6-chloro-2-indolinone
• (241) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (quinolin-6-yl) methylene} -6-chloro-2-indolinone
• s (242) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (benzothiazol-5-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (243) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (benzothiazol-5-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (244) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (benzothiazol-5-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (245) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (benzothiazol-5-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (246) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (benzothiazol-5-yl) methylene} -6-methoxycarbonyl -2-indolinone
• (247) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (benzothiazol-5-yl) - methylene} -6-methoxycarbonyl-2-indolinone
• (248) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (benzothiazol-5-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (249) 3- (Z) - {1- [4- (N-acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (benzothiazol-5-yl) -methylene} -6 methoxycarbonyl-2-indolinone
• (250) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (benzothiazol-5-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (251) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (benzothiazol-5-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (252) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (benzothiazol-5-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (253) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylamino-ethyl-carbonyl} -amino) -phenylamino] -1- (benzothiazol-5-yl) -methylene} -6-methoxycarbonyl-2-indolinone
• (254) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (benzothiazol-5-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (255) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenyiamino] -1- (benzothiazol-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (256) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (benzothiazol-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• s (257) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (benzothiazol-6-yl) methylene} -6-methoxycarbonyl-2- indolinone
• (258) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (benzothiazol-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (259) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethyl-carbonyl} amino) phenylamino] -1- (benzothiazol-6-yl) methylene} -6-methoxycarbonyl -2-indolinone
• (260) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (benzothiazol-6-yl) - methylene} -6-methoxycarbonyl-2-indolinone
• (261) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (benzothiazol-6-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (262) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (benzothiazol-6-yl) -methylene} -6 methoxycarbonyl-2-indolinone
• (263) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (benzothiazol-6-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (264) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (benzothiazol-6-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (265) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (benzothiazol-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (266) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylamino-ethyl-carbonyl} -amino) -phenylamino] -1- (benzothiazol-6-yl) -methylene} -6-methoxycarbonyl-2-indolinone
• (267) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (benzothiazol-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (268) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (indol-5-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (269) 3- (Z) - {1- [4- (diethylaminomethyl) phenylamino] -1- (indol-5-yl) methylene} -6-methoxycarbonyl-2-ir2dolinone
• (270) 3- (Z) - {1- [4- (1-Meylpiperazin-4-ylmethyl) phenylamino] -1- (indol-5-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (271) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (indol-5-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (272) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (indol-5-yl) methylene} -6-methoxycarbonyl -2-indolinone
• (273) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (indol-5-yl) - methylene} -6-methoxycarbonyl-2-indolinone
• (274) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (indol-5-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (275) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (indol-5-yl) -methylene} -6 methoxycarbonyl-2-indolinone
• (276) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (indol-5-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (277) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (indol-5-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (278) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (indol-5-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (279) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylamino-ethyl-carbonyl} -amino) -phenylamino] -1- (indol-5-yl) -methylene} -6-methoxycarbonyl-2-indolinone
• (280) 3- (Z) - {1- [4- (1-Methylimidazol-2-y1) phenylamino] -1- (indol-5-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (281) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (phthalazin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (282) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (phthalazin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (283) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (phthalazin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (284) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (phthalazin-6-yl) methylene} -6-methoxycarbonyl-2-indalinone
• (285) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (phthalazin-6-yl) methylene} -6-methoxycarbonyl -2-indolinone
• (286) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (phthalazin-6-yl) - methylene} -6-methoxycarbonyl-2-indolinone
• (287) 3- (Z) - {1- [4- (N-Acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (phthalazin-6-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (288) 3- (Z) - {1- [4- (N-acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (phthalazin-6-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (289) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (phthalazin-6-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (290) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (phthalazin-6-yl) methylene} -6 methoxycarbonyl-2-indolinone
• (291) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (phthalazin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (292) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (phthalazin-6-yl) methyl en} -6-methoxycarbonyl-2-indolinone
• (293) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (phthalazin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (294) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (4-methyl-3,4-dihydro-2H-benzo [1,4] oxazin-7-yl) - methylene} -6-chloro-2-indolinone
• (295) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (4-methyl-3,4-dihydro-2H-benzo [1,4] oxazin-7-yl) - methylene} -6-chloro-2-indolinone
• (296) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (4-methyl-3,4-dihydro-2H-benzo [1,4 ] oxazin-7-yl) -methylene} -6-chloro-2-indolinone
• (297) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (4-methyl-3,4-dihydro-2H-benzo [1,4] oxazin-7-yl) - methylene} -6-chloro-2-indolinone
• (298) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (4-methyl-3,4-dihydro-2H-benzo [1,4] oxazin-7-yl) -methylene} -6-chloro-2-indolinone
• (299) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (4-methyl-3,4 dihydro-2H-benzo [1,4] oxazin-7-yl) -methylene} -6-chloro-2-indolinone
• (300) 3- (Z) - {1- [4- (N-acetyl-N- {2-dimethylamino-ethyl} amino) phenylamino] -1- (4-methyl-3,4-dihydro-2H -benzo [1,4] oxazin-7-y1) -methylene} -6-chloro-2-indolinone
• (301) 3- (Z) - {1- [4- (N-Acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (4-methyl-3,4-dihydro-2H -benzo [1,4] oxazin-7-yl) -methylene} -6-chloro-2-indolinone
• (302) 3- (Z) - {1- [4- (N-methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (4-methyl-3,4-dihydro- 2H-benzo [1,4] oxazin-7-yl) -methylene} -6-chloro-2-indolinone
• (303) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (4-methyl-3,4-dihydro-2N -benzo [1,4] oxazin-7-yl) -methylene} -6-chloro-2-indolinone
• (304) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (4-methyl-3,4-dihydro-2H-benzo [1.4 ] oxazin-7-yl) -methylene} -6-chloro-2-indolinone
• (305) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (4-methyl-3,4-dihydro -2N-benzo [1,4] oxazin-7-yl) methylene} -6-chloro-2-indolinone
• (306) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino} -1- (4-methyl-3,4-dihydro-2H-benzo [1,4 ] oxazin-7-yl) -methylene} -6-chloro-2-indolinone
• (307) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (4-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (308) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (4-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (309) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (4-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (310) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (4-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (311) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (4-pyridyl) methylene} -6-methoxycarbonyl-2 -indolinon
• (312) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (4-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (313) 3- (Z) - {1- [4- (N-acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (4-pyridyl) methylene} -6-methoxycarbonyl -2-indolinone
• (314) 3- (Z) - {1- [4- (N-acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (4-pyridyl) methylene} -6-methoxycarbonyl -2-indolinone
• (315) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (4-pyridyl) methylene} -6-methoxycarbonyl -2-indolinone
• (316) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (4-pyridyl) methylene} -6- methoxycarbonyl-2-indolinone
• (317) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (4-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (318) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (4-pyridyl) methylene} -6 methoxycarbonyl-2-indolinone
• (319) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (4-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (320) 3- (Z) - {1- [4- (Dimethylaminomethyl) phenylamino] -1- (3-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (321) 3- (Z) - {1- [4- (Diethylaminomethyl) phenylamino] -1- (3-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (322) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylmethyl) phenylamino] -1- (3-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (323) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (3-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (324) 3- (Z) - {1- [4- (N-Methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3-pyridyl) methylene} -6-methoxycarbonyl-2 -indolinon
• s (325) 3- (Z) - {1- [4- (N-Methyl-N- {1-methylpiperazin-4-yl-methylcarbonyl} amino) phenylamino] -1- (3-pyridyl) methylene } -6-methoxycarbonyl-2-indolinone
• (326) 3- (Z) - {1- [4- (N-acetyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3-pyridyl) methylene} -6-methoxycarbonyl -2-indolinone
• (327) 3- (Z) - {1- [4- (N-acetyl-N- {3-dimethylamino-propyl} amino) phenylamino] -1- (3-pyridyl) methylene} -6-methoxycarbonyl -2-indolinone
• (328) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethyl} aminocarbonyl) phenylamino] -1- (3-pyridyl) methylene} -6-methoxycarbonyl -2-indolinone
• (329) 3- (Z) - {1- [4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3-pyridyl) methylene} -6-methoxycarbonyl -2-indolinone
• (330) 3- (Z) - {1- [4- (1-Methylpiperazin-4-ylcarbonylmethyl) phenylamino] -1- (3-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (331) 3- (Z) - {1- [4- (N-Methyl-N- {2-dimethylaminoethylcarbonyl} amino) phenylamino] -1- (3-pyridyl) methylene} -6 methoxycarbonyl-2-indolinone
• (332) 3- (Z) - {1- [4- (1-Methylimidazol-2-yl) phenylamino] -1- (3-pyridyl) methylene} -6-methoxycarbonyl-2-indolinone
• (333) 3- (Z) - {1- [3-fluoro-4- (N-methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-chloro-2-indolinone
• (334) 3- (Z) - {1- [3-fluoro-4- (N-methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (335) 3- (Z) - {1- [3-fluoro-4- (N-methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-chloro-2-indolinone
• (336) 3- (Z) - {1- [3-fluoro-4- (N-methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (337) 3- (Z) - {1- [3-fluoro-4- (N-methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (2-thienyl) methylene} -6 chloro-2-indolinone
• (338) 3- (Z) - {1- [3-fluoro-4- (N-methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (2-thienyl) methylene} -6 methoxycarbonyl-2-indolinone
• (339) 3- (Z) - {1- [3-Fluoro-4- (N-methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3-thienyl) methylene} -6 chloro-2-indolinone
• (340) 3- (Z) - {1- [3-fluoro-4- (N-methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (3-thienyl) methylene} -6 methoxycarbonyl-2-indolinone
• (341) 3- (Z) - {1- [3-fluoro-4- (N-methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-chloro-2-indolinone
• (342) 3- (Z) - {1- [3-fluoro-4- (N-methyl-N- {dimethylaminomethylcarbonyl} amino) phenylamino] -1- (quinoxalin-6-yl) methylene} -6-methoxycarbonyl-2-indolinone
• (343) 3- (Z) - {1- [3-fluoro-4- (N-methanesulfonyl-N- {2-dimethylamino-ethyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) - methylene} -6-chloro-2-indolinone
• (344) 3- (Z) - {1- [3-fluoro-4- (N-methanesulfonyl-N- {2-dimethylamino-ethyl} amino) phenylamino] -1- (3,4-methylenedioxyphenyl) - methylene} -6-methoxycarbonyl-2-indolinone
• (345) 3- (Z) - {1- [3-fluoro-4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) - methylene} -6-chloro-2-indolinone
• (346) 3- (Z) - {1- [3-Fluoro-4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3,4-ethylenedioxyphenyl) - methylene} -6-methoxycarbonyl-2-indolinone
• (347) 3- (Z) - {1- [3-fluoro-4- (N-methanesulfonyl-N- {2-dimethylamino-ethyl} amino) phenylamino] -1- (2-thienyl) methylene} -6-chloro-2-indolinone
• (348) 3- (Z) - {1- [3-fluoro-4- (N-methanesulfonyl-N- {2-dimethylamino-ethyl} amino) - phenylamino] -1- (2-thienyl) -methylene} -6-methoxycarbonyl-2-indolinone
• (349) 3- (Z) - {1- [3-fluoro-4- (N-methanesulfonyl-N- {2-dimethylamino-ethyl} amino) phenylamino] -1- (3-thienyl) -methylene} -6-chloro-2-indolinone
• (350) 3- (Z) - {1- [3-fluoro-4- (N-methanesulfonyl-N- {2-dimethylaminoethyl} amino) phenylamino] -1- (3-thienyl) methylene} -6-methoxycarbonyl-2-indolinone
• (351) 3- (Z) - {1- [3-fluoro-4- (N-methanesulfonyl-N- {2-dimethylamino-ethyl} amino) phenylamino] -1- (quinoxalin-6-yl) - methylene} -6-chloro-2-indolinone
• (352) 3- (Z) - {1- [3-fluoro-4- (N-methanesulfonyl-N- {2-dimethylamino-ethyl} amino) phenylamino] -1- (quinoxalin-6-yl) - methylene} -6-methoxycarbonyl-2-indolinone
• (353) 3- (Z) - {1- [1-Methyl-2- (N- {2-dimethylamino-ethyl} -N-methyl-aminocarbonyl) pyrrol-4-yl-amino] -1- (3rd , 4-methylenedioxyphenyl) methylene} -6-chloro-2-indolinone
• (354) 3- (Z) - {1- [1-Methyl-2- (N- {2-dimethylaminoethyl} -N-methylaminocarbonyl) pyrrol-4-y1-amino] -1- (3rd , 4-methylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone
• (355) 3- (Z) - {1- [1-Methyl-2- (N- {2-dimethylamino-ethyl} -N-methylaminocarbonyl) pyrrol-4-yl-amino] -1- (3rd , 4-ethylenedioxyphenyl) -methylene} -6-chloro-2-indolinone
• (356) 3- (Z) - {1- [1-Methyl-2- (N- {2-dimethylamino-ethyl} -N-methyl-aminocarbonyl) pyrrol-4-yl-amino] -1- (3rd , 4-ethylenedioxyphenyl) -methylene} -6-methoxycarbonyl-2-indolinone
• (357) 3- (Z) - {1- [1-Methyl-2- (N- {2-dimethylamino-ethyl} -N-methylaminocarbonyl) pyrrol-4-yl-amino] -1- (2nd thienyl) -methylene} -6-chloro-2-indolinone
• (358) 3- (Z) - {1- [1-Methyl-2- (N- {2-dimethylamino-ethyl} -N-methyl-aminocarbonyl) pyrrol-4-yl-amino] -1- (2nd thienyl) -methylene} -6-methoxycarbonyl-2-indolinone
• (359) 3- (Z) - {1- [1-Methyl-2- (N- {2-dimethylamino-ethyl} -N-methylaminocarbonyl) pyrrol-4-yl-amino] -1- (3rd thienyl) -methylene} -6-chloro-2-indolinone
• (360) 3- (Z) - {1- [1-Methyl-2- (N- {2-dimethylamino-ethyl} -N-methylaminocarbonyl) pyrrol-4-yl-amino] -1- (3rd thienyl) -methylene} -6-methoxycarbonyl-2-indolinone
• (361) 3- (Z) - {1- [1-Methyl-2- (N- {2-dimethylaminoethyl} -N-methylaminocarbonyl) pyrrol-4-ylamino] -1- (quinoxaline -6-yl) methylene} -6-chloro-2-indolinone
• (362) 3- (Z) - {1- [1-Methyl-2- (N- {2-dimethylaminoethyl} -N-methylaminocarbonyl) pyrrol-4-yl-amino] -1- (quinoxaline -6-yl) methylene} -6-methoxycarbonyl-2-indolinone

Claims (10)

Compounds of the general formula

in which X is an oxygen or sulfur atom, R _{1 is} a hydrogen atom or a prodrug residue such as a C _1-4 alkoxycarbonyl or C _2-4 alkanoyl group, R _{2 is} a hydrogen, fluorine, chlorine or bromine atom, a cyano - or nitro group, a carboxy group, a linear or branched C _1-6 alkoxy-carbonyl group, a C _3-6 cycloalkoxy carbonyl or an aryloxycarbonyl group, an allyloxycarbonyl group optionally substituted by one or two methyl groups, a linear or branched C _{1 -3} -alkoxy-carbonyl group, which is terminated in the alkyl part by a phenyl, heteroaryl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino-carbonyl or di- (C _{1 -3-} alkyl) -aminocarbonyl group is substituted, a linear or branched C _2-6 alkoxy-carbonyl group, which is terminal in the alkyl part by a chlorine atom or a hydroxy, C _1-3 alkoxy, amino, C _1-3 -Alkylamino- or di- (C _1-3 alkyl) amino group is substituted, or an aminocarbonyl, C _1-4 alkyl aminocarbo nyl or a di- (C _1-4 -alkyl) -aminocarbonyl group, the alkyl groups, if they have more than one carbon atom, terminated by a hydroxy, C _1-3 -alkoxy or di- (C _1-3 -alkyl) -amino group, R _{3 is} a five- or six-membered heteroaryl group, the 6-membered heteroaryl group having one, two or three nitrogen atoms and the 5-membered heteroaryl group, one optionally substituted by a C _1-3 -alkyl, carboxy- C _1-3 alkyl or phenyl C _1-3 alkyl group substituted imino group, an oxygen or sulfur atom or one optionally substituted by a C _1-3 alkyl, carboxyC _1-3 alkyl or phenyl C _{1 -3-} alkyl group substituted imino group or an oxygen or sulfur atom and additionally a nitrogen atom or an imino group optionally substituted by a C _1-3 alkyl or phenyl-C _1-3 alkyl group, contains an oxygen atom or a sulfur atom and two nitrogen atoms, and also the monocyclis mentioned above In heterocyclic groups, a phenyl ring can be condensed onto two adjacent carbon atoms, the hydrogen atom of a methine group can be substituted by a C _1-3 alkyl, carboxyC _1-3 alkyl, amino, C _1-3 alkylamino, Di (C _1-3 alkyl) amino, phenyl C _1-3 alkyl amino or di (phenyl C _1-3 alkyl) amino group can be replaced and the bond via a carbon atom of the heterocyclic part, a 5- to 6-membered cyclic oxime ether which is linked to the methylidene group via the carbon atom adjacent to the nitrogen atom, or a bicyclic group consisting of a phenyl ring which is linked to the methylidene group and a -O-CH ₂ -O-, -O-CF ₂ -O-, -O-CH ₂ -CH ₂ -O-, -O-CH = CH-O-, -S-CH = N-, -NH-CH = N- , -N = C (C _1-3 alkyl) -NH-, -N = C (carboxy-C _1-3 alkyl) -NH-, -N (C _1-3 alkyl) -CH = N- , -N (carboxy-C _1-3 alkyl) -CH = N-, -N (C _1-3 alkyl) -C (C _1-3 alkyl) = N-, -N = CH-CH = N-, -N = CH-N = CH-, -N = CH-N = C (C _1-3 alkyl) -, -N = CH-N = C (carboxy-C _1-3 alkyl) - , N = CH -CH = CH-, -N = CH-CH = C (C _1-3 alkyl) -, -N = CH-CH = C (carboxy-C _1-3 alkyl) -, -N = N-NH -, -N = NN (C _1-3 alkyl) -, -N = NN (carboxy-C _1-3 alkyl) -, CH = CH-NH-, CH = CH-N (C _1-3 - Alkyl) -, -CH = CH-N (carboxy-C _1-3 alkyl) -, -N = CH-C (O) -N (C _1-3 alkyl) -, -O-CH ₂ -C (O) -N (C _1-3 alkyl) -, -CH = NN = CH-, -OC (O) -CH ₂ -N (C _1-3 alkyl) -, -O-CH ₂ -C (O) -NH-, -O-CH ₂ -CH ₂ -N (C _1-3 alkyl) -, -OC (O) -N (C _1-3 alkyl) -, -OC (O) - NH, -CO-NH-CO or -CO-N (C _1-3 alkyl) -CO bridge, each linked to two adjacent carbon atoms of the phenyl ring R _{4 is} a C _3-7 cycloalkyl group, the methylene group in position 4 of a 6- or 7-membered cycloalkyl group being replaced by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) - amino group or can be replaced by an -NH- or -N (C _1-3 alkyl) group, or a phenyl group substituted by the R _{6 group} in the 3- or 4-position, which is additionally substituted by fluorine, chlorine or , Bromine or iodine atoms, by C _1-5 alkyl, trifluoromethyl, hydroxy, C _1-3 alkoxy, carboxy, C _1-3 alkoxycarbonyl, amino, acetylamino, C _1-3 -Alkyl-sulfonylamino-, aminocarbonyl-, C _1-3 -alkyl-aminocarbonyl-, di- (C _1-3 -alkyl) -aminocarbonyl-, aminosulfonyl-, C _1-3 -alkyl-aminosulfonyl-, di- (C _1-3 alkyl) aminosulfonyl, nitro or cyano groups can be mono- or disubstituted, where the substituents can be the same or different and where R _{6 is} a hydrogen, fluorine, chlorine, bromine or iodine atom, a cyano -, Nitro, amino, C _1-5 alkyl, C _3-7 cycloalkyl, trifluoromethyl, phen yl or heteroaryl group, a tetrazolyl group optionally substituted by a C _1-3 alkyl group: a 2-pyrrolidon-1-yl group in which the methylene group adjacent to the carbonyl group is replaced by an oxygen atom or a -NH- or -N (C _{1 -3} alkyl) group can be replaced, the group of the formula

in which the hydrogen atoms bonded to a nitrogen atom can each independently be replaced by a C _1-3 alkyl group, a group of the formula - (CH ₂ ) _n -CO-R ₈ in R ₈ a hydroxy or C _1-3 alkoxy group, a 5- to 7-membered cycloalkyleneimino group, the methylene group in position 3 or 4 of a 5-, 6- or 7-membered cycloalkyleneimino group being substituted by an amino, C _{1 -3-} alkylamino or di- (C _1-3 -alkyl) -amino group or the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group can be substituted by an oxygen atom, a sulfur atom, a sulfinyl or sulfonyl group, a - NH-, -N (allyl) - or -N (C _1-3 -alkyl) group can be replaced and in the cyclic groups mentioned one or two hydrogen atoms can be replaced by a C _1-3 -alkyl group, a second , 5-Dihydropyrrol-1-yl group or a C _3-7 cycloalkyl group, the methylene group in position 3 or 4 of the 5-, 6- or 7-membered cycloalkyl part by an amino, C _1-3 - Alkylamino or di (C _1-3 alkyl) amino group substituted or the methylene group in position 4 of the 6- or 7-membered cycloalkyl part by egg ne -NH-, -N (allyl) - or -N (C _1-3 alkyl) group can be replaced, and n is one of the numbers 0, 1 or 2, a group of the formula - (CH ₂ ) _o -CO-NR ₉ R ₁₀ , R _{9 represents} a hydrogen atom, an allyl group, a C _1-3 alkyl group optionally substituted by a cyano, carboxy, phenyl or pyridyl group or a C _2-4 terminally substituted by a hydroxy or C _1-3 alkoxy group Alkyl group, R _{10 is} a hydrogen atom, a C _1-3 alkyl group, a C _2-3 alkyl group terminally substituted by a hydroxy, C _1-3 alkoxy, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or a 3- to 7-membered group Cycloalkyl group in which a methylene group can be replaced by an oxygen atom or an -NH or -N (C _1-3 alkyl) group and independently of this a methylene group can be replaced by a carbonyl group, and o one of the numbers 0, 1 or 2 mean a C _1-3 alkyl group substituted by the group R, where R _{7 is} a C _3-7 cycloalkyl group, one of the methylene groups being substituted by an amino, C _1-3 alkylamino or di (C _{1- 3} -alkyl) -amino group or the methylene group in position 3 or 4 of a 5-, 6- or 7-membered cycloalkyl group by an -NH-, -N (allyl) - or -N (C _1-3 -alkyl) - Group can be replaced or in a 5- to 7-membered cycloalkyl group a - (CH ₂ ) ₂ group can be replaced by a -CO-NH group, a - (CH ₂ ) ₃ group by a -NH-CO -NH or -CO-NH-CO group e may be replaced or a - (CH ₂ ) ₄ group may be replaced by an -NH-CO-NH-CO group, where in each case a hydrogen atom bonded to a nitrogen atom may be replaced by a C _1-3 alkyl group, one Aryl or heteroaryl group, a triazolyl group, a hydroxy or C _1-3 alkoxy group, an amino, C _1-7 alkylamino, di (C _1-7 alkyl) amino, N- (C _{1 -3-} alkyl) -allylamino-, phenylamino-, N-phenyl-C _1-3 -alkyl-amino-, phenyl-C _1-3 -alkylamino-, N- (C _1-3 -alkyl) -phenyl-C _1-3 alkylamino or di (phenyl-C _1-3 alkyl) amino group, an allylamino group in which one or two vinyl hydrogen atoms can each be replaced by a methyl group, an ω-hydroxy C _2-3 - alkyl-amino-, N- (C _1-3 -alkyl) -ω-hydroxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _2-3 -alkyl) -amino-, ω- (C _1-3 alkoxy) -C _2-3 alkylamino-N- (C _1-3 alkyl) - [ω- (C _1-3 alkoxy) -C _2-3 alkyl] amino -, Di- [ω- (C _1-3 alkoxy) -C _2-3 alkyl] amino or N- (dioxolan-2-yl) -C _1-3 alkyl amino group, a C _1-3 -alkylcarbonylamino-C _2-3 -alkylamino- or C _1-3 -alkylcarbonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group, a pyridylamino group, a C _{1- 3-} alkylsulfonylamino-, N- (C _1-3 -alkyl) -C _1-3 -alkylsulfonylamino-, C _1-3 -alkylsulfonylamino-C _2-3 -alkylamino or C _1-3 -alkylsulfonylamino-C _{2 -3-} alkyl-N- (C _1-3 -alkyl) -amino group, a hydroxycarbonyl-C _1-3 -alkylamino or N- (C _1-3 -alkyl) -hydroxycarbonyl-C _1-3 -alkyl-amino group , a guanidino group in which one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group, a 2-pyrrolidon-1-yl group in which the methylene group adjacent to the carbonyl group is replaced by an oxygen atom or by an -NH- or -N (C _1-3 alkyl) group can be replaced, a group of the formula -N (R ₁₁ ) -CO- (CH ₂ ) _p -R ₁₂ , in which R _{11 is} a hydrogen atom or an allyl-, C _1-3 -alkyl-, C _1-3 -alkyl-amino-C _2-3 -alkyl- or di- (C _1-3 -alkyl) -amino-C _2-3 alkyl group, p one of the numbers 0, 1, 2 or 3 and R ₁₂ one, amino, C _1-4 alkylamino, allylamino, di-allyl-amino, di- (C _1-4 -alkyl) -amino-, phenylamino-, N- (C _1-4 -alkyl) -phenylamino-, benzylamino-, N- (C _1-3 -alkyl) -benzylamino-, C _1-4 -alkoxy- or 2nd , 5-Dihydropyrrol-1-yl group or a 4- to 7-membered cycloalkyleneimino group, the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group being represented by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 alkyl) -, -N (allyl) -, -N (phenyl) -, -N (C _1-3 alkylcarbonyl) - or -N (benzoyl) - Group can be replaced, or, if n represents one of the numbers 1, 2 or 3, also represent a hydrogen atom, a group of the formula -N (R ₁₃ ) - (CH ₂ ) _q - (CO) _r -R ₁₄ in which R _{13 represents} a hydrogen atom or a C _1-3 alkyl, allyl, C _1-3 alkyl carbonyl, arylcarbonyl, pyridylcarbonyl, Phe nyl-C _1-3 -alkyl-carbonyl-, C _1-3 -alkylsulfonyl, arylsulfonyl or phenyl-C _1-3 -alkylsulfonyl group, q one of the numbers 1, 2, 3 or 4, r the number 1 or, if q is one of the numbers 2, 3 or 4, the number 0 and R _{14 is also} a hydroxy, amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, phenylamino , N- (C _1-4 -alkyl) -phenylamino-, benzylamino-, N- (C _1-4 -alkyl) -benzylamino-, C _1-4 -alkoxy- or C _1-3 -alkoxy-C _{1- 3} -alkoxy group, a di- (C _1-3 -alkyl) -amino-C _1-3 -alkylamino group which is optionally substituted by a C _1-3 alkyl group or a 4- to 7-membered cycloalkyleneimino group, the Cycloalkylene part can be condensed with a phenyl ring or in each case the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 alkyl) ) -, -N (phenyl) -, -N (C _1-3 alkylcarbonyl) - or -N (benzoyl) - group can be replaced, mean a C _4-7 cycloalky lamino-, C _4-7 -cycloalkyl-C _1-3 -alkylamino- or C _4-7 -cycloalkenylamino group, in which the position 1 of the ring is not involved in the double bond and wherein the groups mentioned above are each added to the amine nitrogen atom by a C _5-7 cycloalkyl, C _2-4 alkenyl or C _1-4 alkyl group may be substituted, a 2,5-dihydro-pyrrol-1-yl group or a 4- to 7-membered cycloalkyleneimino group in which the cycloalkylene part with a phenyl group or with an oxazolo, imidazolo, optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, C _1-3 alkyl, C _1-3 alkoxy or amino group , Thiazolo, pyridino, pyrazino or pyrimidino group can be condensed or / and one or two hydrogen atoms each by a C _1-3 alkyl, C _3-7 cycloalkyl, hydroxy, C _1-3 alkoxy , Hydroxy-C _1-3 alkyl, C _1-3 alkoxy-C _1-3 alkyl or phenyl group can be replaced or / and the methylene group in position 3 of a 5-membered n Cycloalkylenimino group can be substituted by a hydroxy, hydroxyC _1-3 alkyl, C _1-3 alkoxy or C _1-3 alkoxyC _1-3 alkyl group, in each case the methylene group in position 3 or 4 a 6- or 7-membered cycloalkyleneimino group by a hydroxy, hydroxy-C _1-3 -alkyl-, C _1-3 -alkoxy-, C _1-3 -alkoxy-C _1-3 -alkyl-, carboxy-, C _1-4 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocarbonyl-, di- (C _1-3 -alkyl) -aminocarbonyl-, di- (C _1-3 -alkyl) -amino-, phenyl-C _{1 -3} -alkylamino- or N- (C _1-3 alkyl) phenyl-C _1-3 alkylamino group substituted or the methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group by an oxygen or sulfur atom, by a Sulfinyl-, Sulfonyl-, -NH-, -N (C _1-3 -alkyl) -, -N (allyl) -, -N (phenyl) -, -N (phenyl-C _1-3 -alkyl) -, -N (C _1-3 -alkyl-carbonyl) -, -N (C _1-3 -hydroxy-carbonyl) -, -N (C _1-4 -alkoxy-carbonyl) -, -N (benzoyl) - or - N (phenyl-C _1-3 alkyl carbonyl) group can be replaced, one with an imino stick Substance atom of the cycloalkyleneimino group linked methylene group can be replaced by a carbonyl or sulfonyl group or in a 5- to 7-membered monocyclic or fused with a phenyl group cycloalkyleneimino group both methylene groups linked to the imino nitrogen atom can each be replaced by a carbonyl group, or R ₆ a group of the formula -N (R ₁₅ ) -CO- (CH ₂ ) _s -R ₁₆ in R _{15 is} a hydrogen atom, an allyl, C _1-3 alkyl, C _3-7 cycloalkyl or pyridinyl group, one terminal by a phenyl, heteroaryl, trifluoromethyl, aminocarbonyl, C _{1- 4} -alkylamino-carbonyl-, di- (C _1-4 -alkyl) -amino-carbonyl-, C _1-3 -alkyl-carbonyl-, C _1-3 -alkyl-aminosulfonyl- or di- (C _1-3 -alkyl) -aminosulfonyl group substituted C _1-3 alkyl group or a terminally substituted by a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino, allylamino, di (C _1-3 - alkyl) -amino-, C _1-3 -alkyl-sulfonylamino- or N- (C _1-3 -alkyl) -C _1-3 -alkyl-sulfonylamino group substituted C _2-3 -alkyl group and s one of the numbers 0, 1 , 2 or 3 and R _{16 has} the meanings of the aforementioned group R ₇ or a carboxy group or, if s represents one of the numbers 1, 2 or 3, also represents a hydrogen atom, a group of the formula -N (R ₁₇ ) -SO ₂ -R ₁₈ , in which R _{17 represents} a hydrogen atom, an allyl, C _1-4 alkyl or cyanomethyl group or a terminal through a cyano, amino, C _1-3 alkylamino, di (C _1-3 alkyl) - amino, trifluoromethyl-carbonyl-amino or N- (C _1-3 alkyl) -trifluoromethylcarbonyl-amino group substituted C _2-4 alkyl group and R _{18 is} a C _1-3 alkyl, phenyl or pyridyl group, one by a di (C _1-3 alkyl) amino-C _1-3 alkyl carbonyl - Or di- (C _1-3 alkyl) amino-C _1-3 alkyl sulfonyl group and a di- (C _1-3 alkyl) aminocarbonyl-C _1-3 alkyl group substituted amino group, or a group of the formula -A- (CH ₂ ) _t -R ₁₉ in which A is an oxygen or sulfur atom or a sulfinyl or sulfonyl group, R _{19 is} a hydrogen atom, a hydroxyl, C _1-3 alkoxy, aryl, heteroaryl, amino, C _1-3 alkylamino or di - (C _1-3 alkyl) amino group or a 4- to 7-membered cycloalkyleneimino group, the methylene group in position 3 of a 5-membered cycloalkyleneimino group being replaced by a hydroxy, hydroxyC _1-3 alkyl, C _{1- 3} -alkoxy-C _1-3 -alkyl group may be substituted, in each case the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group by a hydroxy-, hydroxy-C _1-3 -alkyl-, C _1-3 - Alkoxy-, C _1-3 -alkoxy-C _1-3 -alkyl-, carboxy-, C _1-4 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocarbonyl- or di- (C _1-3 -alkyl) -aminocarbonyl group substituted or by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH or -N (C _1-3 alkyl) - group, and t one of the numbers 2 or 3 or, if R _{19 is} a hydrogen atom, an aryl or Heteroaryl group also represents the number 1 or, if A represents a sulfonyl group, also the number 0, or a group of the formula -SO ₂ -N (R ₂₀ ) - (CH ₂ ) _u -R ₂ , in which R _{20 is} a hydrogen atom, an allyl or C _1-3 alkyl group, R _{21 is} a hydrogen atom, a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or a di ( C _1-3 -alkyl) -amino group and u one of the numbers 2, 3 or 4 or, if R _{2 is} a hydrogen atom, also the number 1, all of the phenyl groups in the radicals mentioned under R _{6 being} simply bonded or fused on by fluorine, chlorine, bromine or iodine atoms, by C _1-5 alkyl, trifluoromethyl, hydroxy, C _1-3 alkoxy, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl , C _1-4 -alkylamino-carbonyl-, di- (C _1-4 -alkyl) -amino-carbonyl-, aminosulfonyl-, C _1-3 -alkyl-aminosulfonyl-, di- (C _1-3 -alkyl) aminosulfonyl, C _1-3 alkylsulfonylamino, nitro or cyano groups can be mono- or disubstituted, where the substituents can be the same or different, or two adjacent hydrogen atoms of the phenyl groups can be replaced by a methylenedioxy group, or R ₄ a group of formula

in which R _{22 is} a C _1-3 alkyl group, R _{23 is} a hydrogen atom, an allyl group, a C _1-4 alkyl group optionally substituted by a cyano, carboxy, phenyl or pyridyl group or a terminally substituted by a hydroxyl or C _1-3 alkoxy group substituted C _2-4 alkyl group and R _{24 is} a hydrogen atom, a C _1-3 alkyl group, one terminal by a hydroxy, C _1-3 alkoxy, C _1-3 alkylamino or di - (C _1-3 alkyl) amino group substituted C _2-3 alkyl group, or a 3-7 membered cycloalkyl group, where a methylene group by an oxygen atom or by a -NH- or -N (C _1-3 alkyl ) Group he can be and independently of which a methylene group can be replaced by a carbonyl group, or R ₂₃ and R ₂₄ together with the nitrogen atom to which they are linked form a 2,5-dihydro-pyrrol-1-yl group or a 5- to 7-membered cycloalkyleneimino group, the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group being substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or by an oxygen atom, a sulfur atom, a sulfinyl or sulfonyl group or an -NH or -N (C _1-3 alkyl) group can be replaced and wherein one or two hydrogen atoms in the 5- to 7-membered cycloalkyleneimino group can be replaced by a C _1-3 alkyl group can be replaced, and R _{5 represents} a hydrogen atom or a C _1-3 alkyl group, where the expression an aryl group means one optionally by a fluorine, chlorine, bromine or iodine atom, by a cyano, Trifluoromethyl, nitro, carboxy, aminocarbonyl, C _1-3 alkyl or C _1-3 alkoxy group mono- or disubstituted phenyl or naphthyl group and under the expression a heteroaryl group, unless stated otherwise, a monocyclic group optionally substituted by one or two C _1-3 alkyl groups in the carbon skeleton 5- or 6-membered heteroaryl group, the 6-membered heteroaryl group having one, two or three nitrogen atoms and the 5-membered heteroaryl group being an imino group optionally substituted by a C _1-3 alkyl or phenylC _1-3 alkyl group Oxygen or sulfur atom or an imino group optionally substituted by a C _1-3 alkyl or phenyl C _1-3 alkyl group or an oxygen or sulfur atom and additionally a nitrogen atom or one optionally substituted by a C _1-3 alkyl or Phenyl-C _1-3 alkyl group contains substituted imino group and two nitrogen atoms, and also to the above-mentioned monocyclic heterocyclic groups via two adjacent Ko A phenyl ring can be fused onto the hydrogen atom, the hydrogen atom of one or two methine groups can be replaced by a C _1-3 alkyl, amino, C _1-3 alkyl amino or di (C _1-3 alkyl) amino group can and the bond takes place via a nitrogen atom or via a carbon atom of the heterocyclic part or a fused phenyl ring, is to be understood, the hydrogen atoms in the alkyl and alkoxy groups mentioned above or in the alkyl parts contained in the groups of formula I defined above through partially or completely Fluorine atoms can be replaced, the saturated alkyl and alkoxy parts present in the groups defined above, which contain more than two carbon atoms, including their branched isomers, such as the isopropyl, tert-butyl, isobutyl group, unless stated otherwise , and wherein additionally the hydrogen atom of an existing carboxy group or a water bound to a nitrogen atom eratom atom, for example an amino, alkylamino or imino group or a saturated N-heterocycle such as the piperidinyl group, can in each case be replaced by a residue which can be split off in vivo, their tautomers, their diastereomers, their enantiomers, their mixtures, their prodrugs and their salts , Compounds of the general formula I according to claim 1, in which X is an oxygen atom, R _{1 is} a hydrogen atom or a prodrug residue such as a C _1-3 alkoxycarbonyl or C _2-4 alkanoyl group, R _{2 is} a hydrogen, fluorine or chlorine - Or bromine atom, a cyano or nitro group, a carboxy group, a linear or branched C _1-4 alkoxycarbonyl group or a C _3-4 cycloalkoxy carbonyl group, an allyloxycarbonyl group optionally substituted by one or two methyl groups, a linear or branched C _2-3 alkoxy-carbonyl group which is terminally substituted in the alkyl part by a hydroxy or C _1-3 alkoxy group, or an aminocarbonyl, C _1-4 alkyl aminocarbonyl or a di (C _1-3 -alkyl) -aminocarbonyl group, where the alkyl groups, if they have more than one carbon atom, can be terminally substituted by a C _1-3 alkoxy group, R _{3 is} a 2-pyrrolyl, 3-pyrrolyl, 1- (C _{1- 3-} alkyl) -3-pyrrolyl-, 1- (carboxy-C _1-3 -alkyl) -3-pyrrolyl-, 2-furyl-, 3 -Furyl-, 2-thienyl-, 3-thienyl-, 2- (carboxy-C _1-3 -alkyl) -thien-5-yl-, 2- (carboxy-C _1-3 -alkyl) -thien-4 -yl-, 4-imidazolyl-, 1- (C _1-3 -alkyl) -5-imidazolyl-, 1- (C _1-3 -alkyl) -4-imidazolyl-, 1-benzyl-5-imidazolyl-, 5- (C _1-3 alkyl) -isoxazol-3-yl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 4-pyridazinyl group or a pyrazol-3-yl group in which the 1- and / or 5-position independently of one another can each be substituted by a C _1-3 alkyl or carboxy-C _1-3 alkyl group, a 5- to 6 -linked cyclic oxime ether which is linked to the methylidene group via the carbon atom adjacent to the nitrogen atom, or a bicyclic group consisting of a phenyl ring which is linked to the methylidene group and a -O-CH ₂ -O-, -O-CF ₂ O-, -O-CH ₂ -CH ₂ -O-, -O-CH = CH-0-, -S-CH = N-, -NH-CH = N-, -N = C (C _1-3 -Alkyl) -NH-, -N = C (carboxy-C _1-3 -alkyl) -NH-, -N (C _1-3 -alkyl) -CH = N-, -N (carboxy-C _1-3 -alkyl) -CH = N-, -N (C _1-3 -alkyl) -C (C _1-3 -alkyl) = N-, -N = CH-CH = N-, -N = CH-N = CH-, -N = CH-N = C (C _1-3 alkyl) -, -N = CH-CH = CH-, -N = CH-CH = C (C _1-3 alkyl) -, - CH = NN = CH-, -CH = CH-NH-, -CH = CH-N (C _1-3 alkyl) -, -N = N-NH-, -N = NN (C _1-3 alkyl ) -, -O-CH ₂ C (O) -N (C _1-3 alkyl) -, -OC (O) - CH ₂ N (C _1-3 alkyl) -, -OC (O) -N (C _1-3 alkyl) -, -OC (O) -NH-, -O-CH ₂ CH ₂ N (C _1-3 alkyl) -, or -CO-N (C _1-3 alkyl) - CO-B back, which is each linked to two adjacent carbon atoms of the phenyl ring, R _{4 is} a 1-methyl-piperidin-4-yl group, or a phenyl group substituted by the group R ₆ in the 3- or 4-position, which is additionally in a still remaining 3, 4 or 5 positions by a fluorine, chlorine, bromine or iodine atom or by a C _1-3 - alkyl, trifluoromethyl, hydroxy, C _1-3 alkoxy, amino, Nitro or cyano group can be substituted, wherein R _{6 is} a hydrogen, fluorine, chlorine, bromine or iodine atom, a tetrazolyl group optionally substituted by a C _1-3 alkyl group, one on the imino nitrogen and / or on a carbon atom by a C _1-3 alkyl group substituted imidazolyl group, one on the imino nitrogen and / or on one or two carbon atoms each independently substituted by a C _1-3 alkyl group pyrazolyl group, a 2-pyrrolidon-1-yl group, in which that of the carbonyl group neighboring methylene group through an oxygen atom o which can be replaced by a -NH or -N (C _1-3 alkyl) group, a group of the formula - (CH ₂ ) _n -CO-R ₈ , in R _{8 is} a hydroxyl group, a 2,5-dihydropyrrol-1-yl group or a 5- to 7-membered cycloalkyleneimino group, the methylene group in position 3 or 4 of a 5-, 6- or 7-membered cycloalkyleneimino group being replaced by a Amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group may be substituted or the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group by an oxygen atom, a sulfur atom, a sulfinyl or sulfonyl group, an -NH- or -N (C _1-3 -alkyl) group can be replaced and in the cyclic groups mentioned one or two hydrogen atoms can be replaced by a C _1-3 -alkyl group, and n one of the Numbers 0 or 1 mean a group of the formula - (CH ₂ ) _o -CO-NR ₉ R ₁₀ , R _{9 represents} a hydrogen atom, an allyl group, a C _1-3 alkyl group optionally substituted by a cyano or carboxy group or a C _2-4 alkyl group terminally substituted by a hydroxy or C _1-3 alkoxy group, R ₁₀ Hydrogen atom, a C _1-3 alkyl group, a C _2-3 terminally substituted by a hydroxy, C _1-3 alkoxy, C _1-3 alkylamino or di (C _1-3 alkyl) amino group -Alkylgruppe or a 3- to 7-membered cycloalkyl group in which a methylene group can be replaced by an oxygen atom or an -NH- or -N (C _1-3 -alkyl) group, and o is one of the numbers 0 or 1 , a C _1-2 alkyl group substituted by the group R, where R _{7 is} a C _3-7 cycloalkyl group, where the methylene group in position 4 of a 6- or 7-membered cycloalkyl group can be replaced by a -NH or -N (C _1-3 alkyl) group or a pyridyl or optionally substituted by a C _1-3 alkyl group Imidazolyl group, a triazolyl group, a hydroxy or C _1-3 alkoxy group, an amino, C _1-4 alkylamino, di (C _1-3 alkyl) amino, N- (C _1-3 - Alkyl) allylamino, phenyl-C _1-2 alkylamino or N- (C _1-3 alkyl) phenyl-C _1-2 alkylamino group, an allylamino group in which one or two vinyl hydrogen atoms are each represented by a methyl group can be replaced, a ω-hydroxy-C _2-3 alkylamino, N- (C _1-3 alkyl) -ω-hydroxy-C _2-3 alkylamino, di- (ω-hydroxy -C _2-3 alkyl) amino, ω- (C _1-3 alkoxy) -C ₂ alkyl _3-amino-N- (C _1-3 alkyl) - [ω- (C _{1- 3-} alkoxy) -C _2-3 alkyl] amino or di- [ω- (C _1-3 alkoxy) -C _2-3 alkyl] amino group, a pyridylamino group, an N- (C _{1- 3-} alkyl) -C _1-3 -alkylsulfonylamino group, a hydroxycarbonyl-C _1-3 -alkylamino- o the N- (C _1-3 -alkyl) -hydroxycarbonyl-C _1-3 -alkyl-amino group, a 2-pyrrolidon-1-yl group in which the methylene group adjacent to the carbonyl group is replaced by an oxygen atom or a -NH- or -N (C _1-3 alkyl) group can be replaced, a group of the formula -N (R ₁₁ ) -CO- (CH ₂ ) _p -R ₁₂ , in which R _{11 represents} a hydrogen atom or an allyl, C _1-3 alkyl group, C _1-3 alkylamino C _2-3 alkyl or di (C _1-3 alkyl) amino C _2-3 -alkyl group, p one of the numbers 0, 1 or 2 and R _{12 is} an amino, C _1-3 alkylamino, allylamino, di (C _1-2 alkyl) amino, C _1-3 alkoxy - or 2,5-dihydro-pyrrol-1-yl group or a 4- to 7-membered cycloalkyleneimino group, the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group being represented by an oxygen or sulfur atom, by an -NH -, -N (allyl) - or -N (C _1-3 alkyl) group can be replaced, or, if n represents one of the numbers 1 or 2, also represents a hydrogen atom, a group of the formula -N (R ₁₃ ) - (CH ₂ ) _q - (CO) _r -R ₁₄ in which R _{13 is} a hydrogen atom or a C _1-3 alkyl or pyridylcarbonyl group, q is one of the numbers 1 or 2, r is the number 1 or, if q is the number 2, the number 0 and R _{14 is} a hydroxy, Amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, C _1-3 alkoxy group or a 4- to 7-membered cycloalkyleneimino group, the methylene group in position 4 of a 6th - or 7-membered cycloalkyleneimino group by an oxygen or sulfur atom, which can be replaced by an -NH or -N (C _1-3 alkyl) group, mean a C _4-7 cycloalkylamino, C _3-5 -Cycloalkyl-C _1-2 -alkylamino- or C _4-7 -cycloalkenylamino group, in which position 1 of the ring is not involved in the double bond and where the above-mentioned groups are each additionally added to the amine nitrogen atom by a C _2-4 -alkenyl- or C _1-3 alkyl group may be substituted, a 2,5-dihydro-pyrrol-1-yl group or a 4- to 7-membered cycloalkyleneimino group in which one or two hydrogen atoms toms can each be replaced by a C _1-3 alkyl, hydroxy, C _1-3 alkoxy, hydroxy C _1-3 alkyl or C _1-3 alkoxy C _1-3 alkyl group / and in each case the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group is substituted by a carboxy, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 alkyl) aminocarbonyl group or the methylene group in the 4-position of a 6- or 7-membered cycloalkylenimino nappy through an oxygen or sulfur atom, through a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl-) -, -N (allyl) - or -N (C _1-3 -alkyl-carbonyl) - group can be replaced, wherein a methylene group linked to an imino nitrogen atom of the cycloalkyleneimino group can be replaced by a carbonyl or sulfonyl group, or R ₆ denotes a group of the formula -N (R ₁₅ ) -CO- (CH ₂ ) _s -R ₁₆ in R _{15 is} a hydrogen atom, an allyl, C _1-4 alkyl, C _3-5 cycloalkyl or pyridinyl group, one terminally by a pyridyl, trifluoromethyl or di (C _1-2 alkyl) - amino-carbonyl group substituted C _1-3 alkyl group or a terminally substituted by a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group C _2-3 alkyl group and s represent one of the numbers 0, 1, 2 or 3 and R _{16 represents} a hydroxy, C _1-3 alkoxy, carboxy, amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, 2,5-dihydropyrrol-1-yl or pyridinyl group or a 5- to 7-membered cycloalkyleneimino group, the methylene group in position 3 of a 5-membered cycloalkyleneimino group being replaced by a hydroxy , Hydroxy-C _1-3 alkyl or C _1-3 alkoxy-C _1-3 alkyl group may be substituted, in each case the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group by a di- (C _1-3 - alkyl) amino, hydroxy, hydroxy-C _1-3 - alkyl, C _1-3 alkoxy or C _1-3 alkoxy-C _1-3 alkyl group substituted or the methylene group in the 4-position of a 6- or 7-membered cycloalkyleneimino group by an oxygen or sulfur atom, by an -NH or -N (C _{1 -3} alkyl -) - group can be replaced, or, if s represents one of the numbers 1, 2 or 3, also represents a hydrogen atom, a group of the formula -N (R ₁₇ ) -SO ₂ -R ₁₈ , in which R _{17 represents} a hydrogen atom, a C _1-3 alkyl or cyanomethyl group or a C ₂ terminally substituted by a cyano, amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group _-3 alkyl group and R _{18 is} a C _1-4 alkyl or pyridyl group, or a group of the formula -A- (CH ₂ ) _t -R ₁₉ in which A is an oxygen or sulfur atom or a sulfinyl or sulfonyl group, R _{19 is} a hydrogen atom or a hydroxy, C _1-3 alkoxy, amino, C _1-4 alkylamino or di (C _1-3 alkyl ) amino group or a 4- to 7-membered cycloalkyleneimino group, where the methylene group in position 3 or 4 of a 6- or 7-membered group is represented by an oxygen or sulfur atom, by an -NH- or -N (C _1-3 alkyl- ) - Group can be replaced, and t is one of the numbers 2 or 3 or, if R _{19 is} a hydrogen atom, also the number 1 or a group of the formula -SO ₂ -N (R ₂₀ ) - (CH ₂ ) _u R _21, in which R _{20 is} a hydrogen atom or an allyl or C _1-3 alkyl group, R _{2 1 is} a hydrogen atom, a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or a di- (C _1-3 alkyl) amino group and u is one of the numbers 2, 3 or 4 or, if R _{2 is} a hydrogen atom, also the number 1, or R _{4 is} a group of the formula

in which R _{22 is} a methyl group, R _{23 is} a hydrogen atom or an allyl or C _1-3 alkyl group and R _{24 is} a hydrogen atom, a C _1-3 alkyl group or a terminal group through a hydroxy, C _1-3 alkoxy , C _1-3 alkylamino group or C _2-3 alkyl group substituted by a di (C _1-3 alkyl) amino group, or R ₂₃ and R ₂₄ together with the nitrogen atom to which they are linked form a second , 5-dihydro-pyrrol-1-yl group or a 5- to 7-membered cycloalkyleneimino group, the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group being replaced by an amino, C _1-3 alkyl amino or di (C _1-3 alkyl) amino group substituted or can be replaced by an oxygen atom, an -NH- or -N (C _1-3 alkyl) group, and R _{5 represents} a hydrogen atom, where the hydrogen atoms in the alkyl and alkoxy groups mentioned above or in the alkyl parts contained in the groups of formula I defined above can be replaced in whole or in part by fluorine atoms, the saturated alkyl and alkoxy parts present in the groups defined above, which contain more than 2 carbon atoms, including their branched isomers, such as the isopropyl, tert-butyl, isobutyl group, unless stated otherwise, their tautomers, their diastereomers, their enantiomers, their mixtures, their prodrugs and their salts , Compounds of the general formula I according to claim 2, in which X is an oxygen atom, R ₁ and R _{5 are} each a hydrogen atom, R _{2 is} a hydrogen, fluorine, chlorine or bromine atom, a cyano group or a carboxy- C _1-2 alkoxycarbonyl- , Allyloxycarbonyl, C _1-3 - alkylaminocarbonyl or di- (C ₁ _ ₂ alkyl) -aminocarbonyl group R _{3 is} a 2-pyrrolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl , 4-imidazolyl -, 5- (C _1-3 - alkyl) -pyrazol-3-yl-, 5- (C ₁ _ ₃ -alkyl) -isoxazol-3-yl-, 3-pyridyl-, 4-pyridyl -, 2-pyrazinyl, 4-pyridazinyl, benzimidazol-5-yl, 1- (C _1-3 alkyl) benzimidazol-5-yl, 2- (C _1-3 alkyl) benzimidazole 5-yl-, 3,4-methylenedioxy-1-phenyl, 3,4-ethylenedioxy-1-phenyl-, 3,4- (difluoromethylenedioxy) -1-phenyl-, 2- (C _1-3 alkyl) - isoindol-1,3-dione-5-yl-, quinoxalin-6-yl- or 1- (C _1-3 -alkyl) -benzotriazol-5-yl group, R ₄ a by the group R ₆ in 3- or 4-position substituted phenyl group, in the remaining 3- or 4-position additionally by a fluorine or chlorine atom or by a (C _1-3 -) alkoxy or cyano group, where R _{6 is} a 1- (C _1-3 alkyl) imidazol-2-yl group, a 5- (C ₁ _ _3- alkyl) -pyrazol-1-yl group, which can additionally be substituted in the 3-position by a C ₁ _ ₃ -alkyl group, a pyrrolid-2-one-1-yl group, one terminally by the group R ₇ substituted C _1-2 alkyl group, where R _{7 is} an amino, allylamino, C _1-4 alkylamino or di (C _1-3 alkyl) amino group, an ω-hydroxy-C _2-3 alkyl -amino-, N- (C _1-3 -alkyl) -ω-hydroxy-C ₂ _ ₃ -alkyl-amino-, ω- (C _1-3 -alkoxy) -C ₂ _ ₃ -alkyl-amino- or N- (C _1-3 -alkyl) - [- (C _1-3 -akoxy) -C _2-3 alkyl] -amino group, a pyridylamino group, a 5- to 7-membered cycloalkyleneimino group in which a carbon atom with may be substituted by a hydroxy or hydroxymethyl group, the substitution being excluded by a hydroxyl group on a carbon atom adjacent to the nitrogen atom, a 6- to 7-membered cycloalkyleneimino group in which d he methylene group in the 4-position can be replaced by an oxygen atom or an -NH-, -N- (allyl) - or -N (C _1-3 -alkyl) - group, or one via the nitrogen atom in the 1-position or 2 -Position bonded triazolyl group, or R ₆ a group of the formula - (CH ₂ ) _n -CO-R ₈ in which R _{8 is} pyrrolidino, 2,5-dihydro-pyrrol-1-yl, piperidino, morpholino, thiomorpholino or a piperazino or perhydro in the 4-position optionally substituted by a C _1-3 alkyl group 1,4-diazepino group and n is one of the numbers 0 or 1, a group of the formula -CO-NR ₉ R ₁₀ in which R _{9 is} a hydrogen atom, an allyl group or a C _1-3 alkyl group which is optionally terminally substituted by a cyano group and R _{10 is} a hydrogen atom, a C _1-3 alkyl group, a C _2-3 alkyl group terminally substituted by a C _1-3 alkylamino or di (C _1-3 alkyl) amino group or a 3- to 7-membered cycloalkyl group in which a methylene group is replaced by a -NH- or -N (C _1-3 alkyl) group can be replaced, mean a group of the formula -N (R ₁₅₆ ) -CO- (CH ₂ ) _s -R ₁₆ in which R _{15 is} a hydrogen atom, an allyl, C _1-3 alkyl, pyridinyl, ω - [(C _1-3 alkyl) amino] -C _2-3 alkyl or ω- [di- (C _1-3 alkyl) amino] _2-3 alkyl group, s is one of the numbers 0, 1 or 2 and R _{16 is} a C _1-3 alkoxy, amino, C _1-3 alkylamino , Di (C _1-3 alkyl) amino or pyridinyl group, a pyrrolidino, 2,5-dihydropyrrol-1-yl, piperidino, morpholino or thiomorpholino group or a 4-position, optionally by a C _{1 -3-} alkyl group substituted piperazino or perhydro-1,4-diazepino group or, if s represents the number 1 or 2, also represents a hydrogen atom, a group of the formula -N (R ₁₇ ) -SO ₂ -R ₁₈ , in which R _{17 is} a hydrogen atom, a C _1-3 alkyl group or a C _2- substituted terminally by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group ₃ -alkyl group and R _{18 represent} a C _1-3 -alkyl group, a group of the formula -SO ₂ - (CH ₂ ) _t -R ₁₉ , in which t is one of the numbers 1, 2 or 3 and R _{19 is} a hydrogen atom or, if n is one of the numbers 2 or 3, is also a di- (C _1-3 -alkyl) -amino group, or a group of the formula -O- (CH ₂ ) _t -R ₁₉ in which t is one of the numbers 1, 2 or 3 and R _{19 is} a hydrogen atom or, if n is one of the numbers 2 or 3, is also a di- (C _1-3 -alkyl) -amino group, or a group of the formula -SO ₂ -NR ₂₀ R ₂₅ , in which R _{20 is} a hydrogen atom or an allyl or C _1-3 alkyl group and R _{25 is} a C _1-3 alkyl group or is replaced by an amino, C _1-3 alkylamino or di (C _1-3 - alkyl) amino group substituted C _2-3 alkyl group mean, where the dialkylamino groups contained in the abovementioned radicals can contain two identical or two different alkyl groups and the saturated alkyl and alkoxy parts contained in the abovementioned radicals, which more than 2 Carbon atoms can be linear or branched, unless otherwise stated, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts. Compounds of general formula I according to claim 3, in which X represents an oxygen atom, R ₁ and R ₅ each represent a hydrogen atom, R _{2 represents} a hydrogen, fluorine or chlorine atom or a methoxycarbonyl, ethoxycarbonyl, dimethylaminocar bonyl, N-ethyl-N-methyl-aminocarbonyl or diethylaminocarbonyl group, R _{3 is} 3,4-methylenedioxy-1-phenyl, 3,4-ethylenedioxy-1-phenyl, quinoxalin-6-yl, benzimidazole 5-yl, 2-methylbenzimidazol-5-yl or 1-methyl-benzimidazol-5-yl group and R _{4 is} a phenyl group substituted in the 4-position by the group R ₆ and additionally in the 3-position by a fluorine - Or chlorine atom or a methoxy group, where R _{6 is} a 1- (C _1-2 alkyl) imidazol-2-yl group, a 3,5-dimethyl-pyrazol-1-yl group, a pyrrolid -2-one-1-yl group, a methyl group substituted by the group R, where R _{7 is} methylamino, ethylamino, isobutylamino, di (C _1-2 alkyl) amino, N- (2- Hydroxyethyl) methylamino or N- (2-methoxyethyl) methylamino group, a pyrrolidino, 3-hydroxypyrrolidino, 2-hydroxymethylpyrrolidino, 4-hydroxypiperidino, morpholino, piperazin-1-yl or 1-methyl -piperazin-4-yl group or a 1,2,4-triazol-1-yl-, 1,2,3-triazol-1-yl- or 1,2,3-triazol-2-yl-g group, or R _{6 is} an N-acetyl-methylamino or N-methoxyacetyl-methylamino group, a group of the formula -CO-R ₈ , in which R ₈ denotes a piperazino or perhydro-1,4-diazepino group optionally substituted by a methyl group in the 4-position, a 4-methyl-piperazin-1-yl-carbonyl-methyl group, a group of the formula -CO-NR ₉ R ₁₀ in which R ₉ denotes a methyl, cyanomethyl or ethyl group and R ₁₀ denotes a methyl, 1-methylpiperidin-4-yl, 2-methylamino-ethyl, 2-dimethylamino-ethyl or 3-dimethylamino-propyl group of the formula -N (R ₁₅ ) -CO- (CH ₂ ) _s -NMe ₂ , in which s is one of the numbers 1 or 2 and R _{15 is a methyl or ethyl group or, if n is the number 2, also a} 3-pyridyl group, a group of the formula -N (R ₁₅ ') -CO- (CH ₂ ) _s -H, in which s is one of the numbers 1 or 2 and R ₁₅ 'is a 2- (dimethylamino) ethyl or 3- (dimethylamino) propyl group, or a group of the formula -N (Me) -CO- (CH ₂ ) _s -R ₁₆ ', in which s is one of the numbers 1 or 2 and R ₁₆ 'is a dimethylamino group or, if s is the number 1, is also a 4- (C _1-2 alkyl) piperazin-1-yl group, a group of formula -N (R ₁₇ ) -SO ₂ -R ₁₈ , in which a) R _{17 represents} a dimethylaminoethyl group and R _{18 represents} a methyl, ethyl or propyl group or in which b) R ₁₇ and R ₁₈ each represent a methyl group, a group of the formula -SO ₂ -N (R ₂₀ ) - (CH ₂ ) _u -NMe ₂ , in which R _{20 is} a hydrogen atom or a methyl group and u is one of the numbers 2 or 3, a group of the formula -SO ₂ -R ₂₆ , in which R _{26 represents} a methyl group or a 2-di (C _1-2 alkyl) amino ethyl group, or a 2 di (C _1-2 alkyl) amino ethoxy group, the Dialkylamino groups contained in the abovementioned radicals can contain two identical or two different alkyl groups, their tautomers, their diastereomers, their enantiomers, their mixtures and their salts. The following compounds of general formula I according to claim 1: (a) 3- (Z) - {1- [4- (dimethylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl) methylene} -6-chloro-2 -indolinone (b) 3- (Z) - {1- (4- [N-methyl-N- (4-methylpiperazin-1-ylmethylcarbonyl) amino] phenylamino) -1- (quinaxalin-6-yl ) -methylene} -6-chloro-2-indolinone (c) 3- (Z) - {1- [4- (N-ethyl-N-methylaminomethyl) phenylamino] -1- (3,4-methylenedioxyphenyl ) -methylene} -6-chloro-2-indolinone (d) 3- (Z) - {1- [4- (N-methyl-N- {2- (dimethylamino) -ethyl-carbonyl} -amino) -phenylamino ] -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluoro-2-indolinone (e) 3- (Z) - {1- [4- (1,2,4-triazol-1-yl- methyl) phenylamino] -1- (1-methyl-benzimidazol-5-yl) -methylene} -6-fluoro-2-indolinone (f) 3- (Z) - {1- [4- (dimethylaminomethyl) phenylamino ] -1- (1-methyl-benzimidazol-5-yl) -methylene} -6-chloro-2-indolinone (g) 3- (Z) - {1- [4- (dimethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6-chloro-2-indolinone (h) 3- (Z) - {1- (4- [N-methanesulfonyl-N- (2-dimethylaminoethyl) amino] phenylamino ) -1- (3,4-diphenylethyl lendioxyphenyl) methylene} -6-chloro-2-indolinone (i) 3- (Z) - {1- [4- (dimethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) methylene} -6- methoxycarbonyl-2-indolinone (j) 3- (Z) - {1- (4- [N-methyl-N- (4-methylpiperazin-1-yl-methylcarbonyl) amino] phenylamino) -1- (3, 4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone (k) 3- (Z) - {1- (4- [N-acetyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1 - (3,4-ethylenedioxyphenyl) methylene} -6-fluoro-2-indolinone (l) 3- (Z) - {1- [4- (ethylaminomethyl) phenylamino] -1- (3,4-ethylenedioxyphenyl) -methylene} -6-fluoro-2-indolinone (m) 3- (Z) - {1- (4- [N-acetyl-N- (3-dimethylaminopropyl) amino] phenylamino) -1- (3, 4-ethylenedioxyphenyl) methylene} -6-chloro-2-indolinone (n) 3- (Z) - {1- (4- [N-propionyl-N- (3-dimethylaminopropyl) amino] phenylamino) -1 - (3,4-ethylenedioxyphenyl) methylene} -6-chloro-2-indolinone (o) 3- (Z) - {1- (4- [N-propionyl-N- (2-dimethylaminoethyl) amino] - phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-chloro-2-indolinone (p) 3- (Z) - {1- (4- [N-acetyl-N- (2-dimethylaminoethyl) amino ] -phenylamino) -1- (3,4-ethylenedioxyphenyl) -methylene} -6-chloro-2-indolinone (q) 3- (Z) - {1- (4- [4-methylpiperazin-1-yl-methyl ] -phenylamino) -1- (3,4-methylenedioxyphenyl) -methylene} -6-chloro-2-indolinone (r) 3- (Z) - {1- (4- [N-methanesulfonyl-N- (2- dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone (s) 3- (Z) - {1- (4- [pyrrolidin-1-yl -methyl] -phenylamino) -1- (3,4-ethylenedioxyphenyl) -methylene} -6-methoxycarbonyl-2-indolinone (t) 3- (Z) - {1- (4- [N-Methyl-N- (dimethylaminomethylcarbonyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone ( u) 3- (Z) - {1- (4- [Ethylamino-methyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone (v) 3- (Z ) - {1- (4- [4-Methylpiperazin-1-ylmethyl] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone (w) 3- (Z ) - {1- (4- [dimethylamino-methyl] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone (x) 3- (Z) - {1- ( 4- [diethylamino-methyl] phenylamino) -1- (3,4-methylenedioxyphenyl) -methylene} -6-methoxycarbonyl-2-indolinone (y) 3- (Z) - {1- [4- (dimethylaminocarbonyl) - phenylamino] -1- (1-methyl-benzimidazol-5-yl) -methylene} -6-fluoro-2-indolinone (z) 3- (Z) - {1- (4- [N-propionyl-N- ( 3-dimethylaminopropyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluoro-2-indolinone (aa) 3- (Z) - {1- (4- [N-propionyl -N- (2-dimethylaminoethyl) -amino] -phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6-fluoro-2-indolino n (ab) 3- (Z) - {1- (4- [N-methanesulfonyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene} -6- fluoro-2-indolinone (ac) 3- (Z) - {1- (4- [N-acetyl-N- (2-dimethylaminoethyl) amino] phenylamino) -1- (3,4-ethylenedioxyphenyl) methylene } -6-methoxycarbonyl-2-indolinone (ad) 3- (Z) - {1- (4- [N-methyl-N- (2-dimethylaminoethyl) aminocarbonyl] phenylamino) -1- (3,4-ethylenedioxyphenyl ) -methylene} -6-methoxycarbonyl-2-indolinone (ae) 3- (Z) - {1- (4- [N-methyl-N- (3-dimethylaminopropyl) aminocarbonyl] phenylamino) -1- (3, 4-ethylenedioxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone (af) 3- (Z) - {1- (4- [N-Methyl-N- (2-dimethylaminoethyl) aminocarbonyl] phenylamino) -1- (3,4-methylenediaxyphenyl) methylene} -6-methoxycarbonyl-2-indolinone and (az) 3- (Z) - {1- (4- [N-methyl-N- (4-methylpiperazin-1-yl- methylcarbonyl) amino] phenylamino) -1- (3,4-methylenedioxyphenyl) methylene} -6-chloro-2-indolinone, their tautomers and their salts. Physiologically acceptable salts of the compounds according to claims 1 to 5th Medicament containing a compound according to at least one of the claims 1 to 5 or a salt according to claim 6 in addition to optionally one or more inert carriers and / or diluents. Use a connection after at least one of claims 1 to 5 or a salt according to claim 6 for the manufacture of a medicament which is used for the treatment of excessive or abnormal cell proliferation is suitable. A method of manufacturing a medicament according to claim 7, characterized in that on non-chemical Ways a connection according to at least one of claims 1 to 5 or a salt according to claim 6 in one or more inert carriers and / or diluents is incorporated. A process for the preparation of the compounds according to claims 1 to 6, characterized in that a. a compound of the general formula

in which X and R _{3 are} as defined in claims 1 to 5, R ₂ 'has the meanings for R ₂ in claims 1 to 5, R _{27 is} a hydrogen atom or a protective group for the nitrogen atom of the lactam group, one of which Residues R ₂ 'and R _{27 may} also represent a bond to a solid phase which may be formed via a spacer and the other of the residues R ₂ and R _{27 has} the meanings mentioned above, and Z, a halogen atom, a hydroxyl, alkoxy or aryl -alkoxy group mean with an amine of the general formula

in which R ₄ and R _{5 are} as defined in claims 1 to 5, is reacted and, if necessary, a protective group used for the nitrogen atom of the lactam group or a compound thus obtained is then cleaved from a solid phase, or b. for the preparation of a compound of the general formula I in which R _{2 is} a linear or branched C _1-6 alkoxycarbonyl group, a C _3-6 cycloalkoxycarbonyl or an aryloxycarbonyl group, an allyioxycarbonyl group optionally substituted by one or two methyl groups, a linear or branched C _1-4 alkoxy-carbonyl group, which in the alkyl part is terminated by a phenyl, heteroaryl, carboxy, C _1-3 alkoxy-carbonyl, aminocarbonyl, C _1-3 alkylamino-carbonyl or di - (C _1-3 alkyl) aminocarbonyl group is substituted, a linear or branched C _2-6 alkoxy carbonyl group, which in the alkyl part is terminally substituted by a chlorine atom or a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group is substituted, or an aminocarbonyl, C _1-4 alkyl aminocarbonyl or a di (C _1-4 alkyl) - aminocarbonyl group, the alkyl groups, if they have more than one carbon atom, terminated by a hydroxy, C _1-3 alkoxy or di (C _{1 -3-} alkyl) -amino group can be substituted means: a compound of the general formula

in which X, R ₁ and R ₃ to R _{5 are defined} as mentioned in claims 1 to 5, or their reactive derivatives with a compound of the general formula H – R28 (V), in R ₂₈ a linear or branched C _1-6 alkanol, a C _3-6 cycloalkanol or an aromatic alcohol, an allyl alcohol optionally substituted by one or two methyl groups, a linear or branched C _1-3 alkanol, the terminal in the alkyl part by a phenyl, heteroaryl, carboxy, C _1-3 alkoxy carbonyl, aminocarbonyl, C _1-3 alkylamino carbonyl or di (C _1-3 alkyl) aminocarbonyl group is substituted, a linear or branched C _2-6 alkanol, the terminal in the alkyl part by a chlorine atom or a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _{1 -3} alkyl) amino group is substituted, or an amino, C _1-4 alkylamino or a di (C _1-4 alkyl) amino group, the alkyl groups, if they have more than one carbon atom , may be terminally substituted by a hydroxy, C _1-3 alkoxy or di (C _1-3 alkyl) amino group means, is reacted, or c. for the preparation of a compound of the general formula

in which X, R ₁ , R ₂ , R ₄ and R _{5 are defined} as mentioned in claims 1 to 5 and R _a and R _{b are} each independently a hydrogen tour, a C _1-3 alkyl group or a carboxy-C _{1 -3} -alkyl group can be: a compound of the general formula

in which X, R ₁ , R ₂ , R ₄ and R _{5 are defined} as mentioned in claims 1 to 5 and R _{a is} a hydrogen atom, a C _1-3 alkyl group or an optionally protected carboxy-C _1-3 alkyl group may be reduced, or d. For the preparation of a compound of the general formula I in which R _{4 is} a phenyl group which is substituted by the group R ₆ in the 3- or 4-position and which can additionally be substituted as described in claim 1, and R _{6 is} a substituted by R ₇ C _1-3 alkyl group, where R _{7 is} a heteroaryl group which is bonded via an imino nitrogen, a hydroxy or C _1-3 alkoxy group, an amino, C _1-7 alkylamino, di (C _{1- 7-} alkyl) -amino-, N- (C _1-7 -alkyl) -allylamino-, phenylamino-, N-phenyl-C _1-3 -alkyl-amino-, phenyl-C _1-3 -alkylamino-, N - (C _1-3 alkyl) phenyl-C _1-3 alkylamino or di (phenyl-C _1-3 alkyl) amino group, an allylamino group in which one or two vinyl hydrogen atoms are each replaced by a methyl group can be an ω-hydroxy-C ₂ _ ₃ -alkylamino-, N- (C _1-3 -alkyl) -ω-hydroxy-C _{2 -3} -alkyl-amino-, di- (ω-hydroxy- C _2-3 alkyl) amino, N- (C _1-3 alkyl) - [ω- (C _1-3 alkoxy) -C _2-3 alkyl] amino, di (ω- (C _1-3 alkoxy) -C ₂ _ _3- alkyl) -amino or N- (dioxolan-2-yl) -C _1-3 -alkyl-amino group, a C _1-3 -alkyl-carbonylamino-C _2-3 -alkyl-amino- or C _{1- 3-} alkyl-carbonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group, a pyridylamino group, a C _1-3 -alkylsulfonylamino-, N- (C _1-3 -alkyl) -C _1-3 -alkylsulfonylamino-, C _1-3 -alkylsulfonylamino-C _2-3 -alkyl-amino- or C _1-3 - Alkylsulfonylamino-C _{2 -3} -alkyl-N- (C _1-3 -alkyl) -amino group, a hydroxycarbonyl-C _1-3 -alkylamino- or N- (C _1-3 -alkyl) -hydroxycarbonyl-C _1-3 -alkyl-amino group, a guanidino group in which one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group, a 2-pyrrolidon-1-yl group in which the methylene group adjacent to the carbonyl group is replaced by an oxygen atom or by a -NH or -N (C _1-3 alkyl) group can be replaced, a group of the formula -N (R ₁₁ ) -CO- (CH ₂ ) _p -R ₁₂ , in which R _{11 is} a hydrogen atom or an allyl-, C _1-3 -alkyl-, C _1-3 -alkyl-amino-C _2-3 -alkyl- or di- (C _1-3 -alkyl) -amino-C _2-3 alkyl group, p one of the numbers 0, 1, 2 or 3 and R ₁₂ an amino, C _1-4 alkylamino, allylamino, di-allyl-amino, di (C _1-4 - alkyl) amino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino, N- (C _1-4 alkyl) benzylamino, C _1-4 alkoxy or 2, 5-dihydropyrrol-1-yl group or a 4- to 7-membered cycloalkyleneimino group, the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group being represented by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, NH-, -N (C _1-3 alkyl) -, -N (allyl) -, -N (phenyl) -, -N (C _1-3 alkylcarbonyl) - or -N (benzoyl) group may be replaced, or, if n represents one of the numbers 1, 2 or 3, also represents a hydrogen atom, a group of the formula -N (R ₁₃ ) - (CH ₂ ) _q - (CO) _r -R ₁₄ , in which R _{13 represents} a hydrogen atom or a C _1-3 alkyl, allyl, C _1-3 alkyl carbonyl, arylcarbonyl, pyridylcarbonyl, phenyl C _1-3 alkyl carbonyl, C _{1- 3-} alkylsulfonyl, arylsulfonyl or phenyl-C _1-3 -alkylsulfonyl group, q one of the numbers 1, 2, 3 or 4, r the number 1 or, if q is one of the numbers 2, 3 or 4, the number 0 and R _{14 are} hydroxy, amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-3 alkyl) phenylamino, Benzylamino, N- (C _1-3 alkyl) benzylamino, C _1-4 alkoxy or C _1-3 alkoxy-C _1-3 alkoxy group, one in the 1-position optionally by a C _{1- 3-} alkyl group substituted di- (C _1-4 -alkyl) -amino-C _1-3 -alkylamino group or a 4- to 7-membered cycloalkyleneimino group, where the cycloalkylene part can be fused with a phenyl ring or the methylene group in position 4 one 6- or 7-membered cycloalkyleneimino group through an oxygen or sulfur atom, through a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -Alkyl) -, -N (phenyl) -, -N (C _1-3 -alkyl-carbonyl) - or -N (benzoyl) - group can be replaced, mean a C _4-7 -cycloalkylamino-, C _{4 -7-} Cycloalkyl-C _1-3 -alkylamino- or C _4-7 -cycloalkenylamino group in which the position 1 of the ring is not involved in the double bond and where the groups mentioned above are each additionally added to the amine nitrogen atom by a C _5-7 - Cycloalkyl, C2-4 alkenyl or C _1-4 alkyl group can be substituted, a 2,5-dihydro-pyrrol-1-yl group or a 4- to 7-membered cycloalkyleneimino group in which the cycloalkylene part with a phenyl group or with an oxazolo, imidazolo, thiazolo, pyridino optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, C _1-3 alkyl, C _1-3 alkoxy or amino group -, Pyrazino or pyrimidino group can be condensed and / or one or two hydrogen atoms each by a C _1-3 alkyl, C _{3 -7} cycloalkyl, hydroxy, C _1-3 alkoxy, hydroxy-C _{1 -3-} alkyl- or C _1-3 alkoxy-C _1-3 alkyl or phenyl group can be replaced or / and the methylene group in position 3 of a 5-membered cycloalkyleneimino group by a hydroxy, hydroxy-C _1-3 alkyl, C _{1 -3} -alkoxy- or C _1-3 -alkoxy-C _1-3 -alkyl group can be substituted, in each case the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group by a hydroxy, hydroxy-C _1-3 -alkyl-, C _1-3 -alkoxy-, C _1-3 -alkoxy-C _1-3 -alkyl-, carboxy-, C _1-4 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocarbonyl-, di - (C _1-3 -alkyl) -aminocarbonyl-, phenyl-C _1-3 -alkylamino- or N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino group substituted or the methylene group in the 4-position a 6- or 7-membered cycloalkyleneimino group through an oxygen or sulfur atom, through a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl) -, -N (allyl) -, -N (phenyl ) -, -N (Phe nyl-C _1-3 -alkyl) -, -N (C _1-3 -alkyl-carbonyl) -, -N (C _1-4 -hydroxy-carbonyl) -, -N (C _1-4 -alkoxy-carbonyl ) -, -N (benzoyl) - or -N (phenyl-C _1-3 alkylcarbonyl) group can be replaced, wherein a methylene group linked to an imino nitrogen atom of the cycloalkyleneimino group can be replaced by a carbonyl or sulfonyl group or in a 5- to 7-membered monocyclic or fused with a phenyl group cycloalkyleneimino group both methylene groups linked to the imino nitrogen atom can each be replaced by a carbonyl group means: a compound of the general formula

in which R ₃ , R ₅ and X are defined as mentioned in claims 1 to 5, R ₂ 'has the meanings mentioned for R ₂ in claims 1 to 5, R _{27 represents} a hydrogen atom or a protective group for the nitrogen atom of the lactam group, where one of the radicals R ₂ 'and R _{27 may} also represent a bond to a solid phase which may be formed via a spacer and the other of the radicals R ₂ ' and R _{27 has} the meanings mentioned above, A is a C _1-3 alkyl group and Z _{2 represents} a leaving group with an amine of the general formula H – R ₇ , (IX), in which R _{7 'has} the meanings given above for R ₇ , is reacted and, if necessary, a protective group used for the nitrogen atom of the lactam group or a compound thus obtained is then split off from a solid phase, and / or if desired subsequently a compound of the general formula so obtained I, which contains an alkoxycarbonyl group, is converted into a corresponding carboxy compound by hydrolysis or a compound of the general formula I thus obtained, which contains an amino or alkylamino group, is converted into a corresponding alkylamino or dialkylamino compound by means of reductive alkylation, or a compound thus obtained of the general formula I, which contains an amino or alkylamino group, is converted into a corresponding acyl or sulfonyl compound by means of acylation or sulfonation or a compound of the general formula I thus obtained which contains a carboxy group lt, is converted into a corresponding ester or aminocarbonyl compound by esterification or amidation or a compound of the general formula I thus obtained, which contains a cycloalkyleneimino group in which a methylene group has been replaced by a sulfur atom, is converted into a corresponding sulfinyl or sulfonyl compound by means of oxidation or a compound of the general formula I thus obtained which contains a nitro group is converted into a corresponding amino compound by reduction or a compound of the general formula I thus obtained in which R ₄ is an amino, alkylamino or aminoalkyl group or N-alkylamino group substituted phenyl group, by reaction with a corresponding cyanate, isocyanate or carbamoyl halide is converted into a corresponding urea compound of the general formula I or a compound of the general formula I thus obtained, in which R ₄ is an amino, alkylamine represents phenyl group substituted by o-, aminoalkyl or N-alkylamino, by means of reaction with a corresponding compound transferring the amidino group or by reaction with a corresponding nitrile into a corresponding guanidino compound of general formula I or, if necessary, during the reactions to protect protective groups used is split off or, if desired, a compound of the general formula I thus obtained is subsequently separated into its stereoisomers or a compound of the general formula I thus obtained into its salts, in particular for the pharmaceutical Application is converted into their physiologically acceptable salts with an inorganic or organic acid or base.