MXPA00010095A - Substituted indolinones, the production thereof and their use as medicaments - Google Patents

Abstract

The invention relates to substituted indolinones of general formula (I) in which R1 to R5 and X are defined as in Claim No. 1, to the isomers thereof, and to their salts, especially to the physiologically compatible salts thereof, which exhibit valuable pharmacological characteristics, especially an inhibiting effect on different kinases and cyclin/CDK complexes, and on the proliferation of different tumor cells. The invention also relates to medicaments containing these compounds, to their use, and to a method for the production thereof.

Description

NEW INDO INDONES REPLACED, ITS PREPARATION AND SP EMPLEO AS MEDICAMENTOS The present invention relates to new substituted indolinones of the general formula R \ its isomers, its salts, in particular its physiologically compatible salts, which have valuable properties. The above compounds of the general formula I, in which Ri represents a hydrogen atom or a prodrug radical, have high pharmacological properties, in particular an inhibitory effect on different kinases, especially on CDK's complexes (CDK1, CDK2, CDK3, CDK4, CDKß, CDK7, CDK8 and CDK9) with their specific cyclins (A, Bl, B2, C, DI, D2, D3, E, F, Gl, G2, H, I and K) and on cyclin virica (see L Mengtao in J. Virology 1 1 (3), 1984-1991 (1997)), and the remaining compounds of the above general formula I, in which Ri does not represent any hydrogen atom, nor any prodrug radical, represent valuable products intermediates for the preparation of the aforementioned compounds. Accordingly, the present invention relates to compounds of the above general formula I, the compounds in which Ri represents a hydrogen atom or a prodrug radical, valuable pharmacological properties, the drugs containing the pharmacological compounds. In the above general formula I, X means an oxygen or sulfur atom, Ri means a hydrogen atom, a C 1-4 alkoxy-carbonyl or C 2-4 alkanoyl group, R 2 means a carboxy or C 1 -4 -alkoxycarbonyl group, or a aminocarbonyl group and is substituted with one or two C? _3 alkyl groups, wherein the substituents may be the same or different, R 3 means a hydrogen atom or a C 1-6 alkyl group, starting from the 2-position referred to the carbon of the group R 3 -C (R 4 NR 5) =, may be substituted with a fluorine, chlorine or bromine atom, with a hydroxy group, C 1 - 3 alkoxy, C 1 --3 - s or phenyl 1, alkyl C 1 - 3-Sulfonyl, C 1 -C 3 -alkylsulfonyl, phenyl sui phenyl, f in i 1 s ul f ini 1, phenylsulfonyl, amino, C 1 -C 3 -amino, di- (C 1-3 alkyl) -amino , C2_5-amino-alkanoyl or N- (C1-3-alkylamino) - on the C 1 -C 2 -sino amino, R 4 means a hydrogen atom, a C 1-6 alkyl group or a Cs_ 7 cycloalkyl group optionally substituted n is a C ?3 alkyl group, in which a methylene group in the 3 or 4 position, referred to the carbon atom of the group R3-C ÍR4NR5) =, can be substituted with an imino group optionally substituted with a C1- alkyl group 3, a phenyl or naphthyl group, which may be substituted with a fluorine, chlorine, bromine or iodine atom, with a methoxy group, optionally substituted with 1 to 3 fluorine atoms, with a C2_3 alkoxy group, in position 2 or 3, it can be substituted with a C alqu-3-amino-alkyl, di- (C 1-3 -alkyl) -amino group or with 1 to 5-membered eimino, wherein, in each case, additionally a part of Alkyl in the aforementioned alkylamino and dialkylamino groups can be substituted with a phenyl group, with a trifluoromethyl group or amino, alkyl C? -3-amino, di- (C? _3 alkyl) -amino, alkanoyl C2_5-amino, N- (C1-3alkyl) -C2-5alkynyl-amino, C1-5alkylsulph1-amino, N- (C1-3alkyl) -C1-5alkyl- su1 f on i 1 ami no, phenyls ul f oni lamino, N- (C1-3 alkyl) -phenylsulphonylamino, aminosulfonyl, alkyl C? _3-a ino-sui f oni 1 oo di- (alkyl C? _3) - ami no s ul f oni 1 or, wherein, in each case, additionally an alkyl part in the aforementioned alkylamino and dialkylamino groups can be substituted with a phenyl group, with a carbonyl group, which is substituted with a hydroxy group, C? _3 alkoxy, amino, C C_3-amino alkyl or N- (C 1-5 alkyl) -Cl 3 -alkylamino, wherein, in each case, additionally an alkyl part in the groups mentioned above may be substituted with a carboxy group, C1-3 alkoxy - ca rboni 1 oo phenyl or, in position 2 or 3, with a di- (C3_3) alkyl group, amino, piperazino, N- (C1_3 alkyl) -piperazi no or ci c 1alkylenei not from 5 to 7 members, with a C1-3 alkyl group, which is substituted with an amino group, C 1 _ 7-a-mino alkyl, C 5 -7-amino-cycloalkyl or phenyl-C 1 -3-amino alkyl, which in each case may be further substituted at the nitrogen atom by a group C1-3 alkyl, in which the hydrogen atoms are partially or completely replaced by fluorine atoms, with a C5_7 cycloalkyl group, C2-4 alkenyl or C1-4 alkyl, wherein the C1-4 alkyl substituent above In each case, it may also be substituted with a cyano, carboxy, C1-3-alkoxycarbonyl or pyridyl, imidazolyl, benz or [1,3] di oxo-1 or phenyl group, wherein the phenyl group may be mono-, di-ters with a fluorine, chlorine or bromine atom, with a methyl, methoxy, trifluoromethyl, cyano or nitro group, and the substituents may be the same or It may be substituted in position 2, 3 or 4 with a hydroxy group, with a C? -3 alkyl group which may be substituted by a hydroxy, carboxy, thool or folic acid, 1-oxide-thio-rhenoxy group. 1 ino, 1,1-dioxido-tismorfolino, piperazino, N- (alkyl C? -) -piperazino or N-fe ni 1 -p ipe raz ino, with a group cic 1 oal quilenimino of 5 to 7 members or with a a group of four or seven members, wherein the groups 1 to 1 or 1 to 5 of the aforementioned members may be substituted with one or two C? _3 alkyl groups, with a C5_7 cycloalkyl group or phenyl , with a C 1-3 alkyl group, C 5-7 cycloalkyl, phenyl, carboxy or C 1-4 alkoxycarbonyl and with a hydroxy group, and in the aforementioned cycloalkyl or iminoquinimino groups a methylene group contiguous to the nitrogen atom may be replaced by a carbonyl group, with an alkyl group C? _3, which is substituted with a cycloalkyleneimino group of 5 to 7 members, being condensed to the aforementioned 5 to 7-membered cycloalkyleneimino groups, through 2 contiguous carbon atoms, a phenyl group optionally mono- or disubstituted with fluorine, chlorine or bromine atoms, with methyl or methoxy groups, which may be the same or different substituents, or an oxazole, imidazole, thiazole, pyridino, pyrazino or pyrimidino group optionally substituted with a group - methyl, methoxy or amino, it being possible for the mono-substituted phenyl groups mentioned above to be substituted with a fluorine, chlorine or bromine atom, with a methyl, methoxy or nitro group, or a 5-membered heteroaromatic group, which contains an imino group, an oxygen or sulfur atom, or an imino group, an oxygen or sulfur atom and a two nitrogen atoms, or a 6-member omatic group, which contains one, two or three nitrogen atoms, wherein the aforementioned 5- and 6-membered heteroaromatic groups can be further substituted with a chlorine atom, or bromine or with a methyl group, or the aforementioned 5- and 6-membered heteroaromatic groups can be condensed phenyl ring through 2 contiguous carbon atoms, and R5 signifies a hydrogen atom or a C ?_3 alkyl group. In addition, the carboxy, amino or imino groups present in a compound of the general formula I above can be substituted with radicals which can be separated in vivo. In this case, in addition to the aforementioned alkoxycarbonyl and alkanoyl groups, radicals which can be separated in vivo such as an acyl group, such as the benzoyl, pyridinoyl, pentanoyl or hexanoyl group, an allyloxycarbonyl group, a C 1-16 alkoxy group - ca rboni 1 o, such as the pentyloxycarbonyl group, xi 1carboxy 1, octyloxycarbonyl, noni 1 oxycarboni 1, cycloxycarbonyl, 1 cycloalkyl 1 , wherein the oxycarbonyl or hexadecyl cylcoxycarbonyl, a phenyl-C6-6-carbonyl alkoxy group, such as the benzyloxycarbonyl group, f-1 and oxylcarbonyl, or phenylp ropoxy cabonyl, an alkyl C3 group. - s ul f on i 1 - a 1 c ox i C2-4 - ca rb on i 1, alkoxy C? -3-alkoxy C2-4-alkoxy C2-4 ~ ca rbon i 1 oo RcC0-O- ( RdCRe) -O-CO, in which Rc represents a C?-C 8 -cycloalkyl C5_7 alkyl group, phenyl of eni 1 - a 1 qui 1 or C ?3, Re represents a hydrogen atom, a Cx_3 alkyl group, cycloalkyl Cs_7 0 phenyl and R 4 represents a hydrogen atom or an alkyl group Cj.-3 or the radical RcCo - or - (RdCRe) -O-, the ester residues mentioned above also being usable as a group transformable in vivo in a carboxy group. Compounds of the general formula I preferred are those in which X means an oxygen atom, Ri means a hydrogen atom, R 2 signifies an aminocarbonyl group, R 3 signifies a hydrogen atom or a C 4 -4 alkyl group which, from of the position 2 referred to the carbon atom of the group R3-C (R4NR5) =, can be substituted with a chlorine or bromine atom or with a phenylsulfonyl group, R4 means a hydrogen atom, a C? -3 alkyl group or a cyclopentyl or cyclohexyl group, optionally substituted with a methyl group, wherein in the cyclopentyl and cyclohexyl group a methylene group in the 3 or 4 position, referred to the carbon atom of the group R3 -C (R4NR5) =, can be "replaced by an imino group optionally substituted with a methyl group, a phenyl group, which may be substituted with a fluorine, chlorine, bromine or iodine atom, with a methoxy group, optionally substituted with 1 to 3 fluorine atoms, with an alkoxy group C2_3 which, in position 2 or 3, can be substituted with a methylamino, dimethylamino or cycloalkyl or 5-6 membered -iminimino group, wherein, in each case, additionally a methyl group in the aforementioned amino groups can be substituted with a phenyl group, with a trifluoromethyl, amino, C2-s-amino-alkanoyl, N- (C1-3 alkyl) -alkanoyl C? -s-amino, C1-5 alkyl-sulphonylamino, N- (C-alkyl) group ? 3) -alkyl C1-5-its 1-onylamino, f-enyl-1-amino-1-amino, N- (C1-3-alkyl) -phenyl-1-sulphonyl amine or aminosulfonyl, wherein, in each case, additionally a part of alkyl in the aforementioned alkylamino and dialkylamino groups may be substituted with a phenyl group, with a carbonyl group, which is substituted with a hydroxy group, C1-3 alkoxy, amino, C1-3-alkyl or N- (a1 qui 1C 1-5) - a 1 qu i 1 C1-3- amino group, wherein, in each case, an alkyl part of the groups mentioned above can be further substituted with a carboxy, C 1 -C 3 alkoxycarbonyl or phenyl group, or, in position 2 or 3, with a difunctional group. - (C C_3 alkyl) -amino, piperazino, N- (C C-alkyl) -piperazino or cycloalkyleneimino of 5-7 members, with a C? -3 alkyl group, which is substituted with an amino group, alkyl C ? -7-amino, Cs-7-amino-cycloalkyl or phenyl-C? _3-amino alkyl, which in each case can be further substituted at the nitrogen atom with a C? _3 alkyl group, in which the hydrogen atoms they are replaced, partially or totally, by fluorine atoms, with a cyclohexyl, C2_4 alkenyl or C1-4 alkyl group, wherein the above-mentioned C1_4 alkyl substituent may be substituted in each case optionally with a cyano, carboxy, C alco-3-carbonyl, pyridyl, imidazolyl, benzo [1, 3] dioxole or phenyl group, the phenyl group being monosubstituted with a fluorine, chlorine or bromine atom, with a methyl group , methoxy, cyano, trifluoromethyl or nitro, or di-substituted with fluorine, chlorine or bromine atoms, with methyl or methoxy groups, and the substituents may be the same or different, or may be substituted in position 2, 3 or 4 with a hydroxy group, with a Ci-3 alkyl group which may be substituted with a hydroxy, carboxy, thiol group, or 1-ox i do-ti omor fo 1 ino, 1,1- di oxido - 1-ring metal, piperazino, N- (C 1 -C 3 alkyl) -piperazino or N-pheny 1 -p ip erazi, with a cycloalkyleneimino group of 5 to 7 members or with a cycloalkyleneimino group of 4 to 7 members , wherein the above-mentioned 5- to 7-membered cycloalkyleneimino groups may be substituted with one or two C? _3 alkyl groups , with a cyclohexyl or phenyl group, with a C3_3 alkyl, cyclohexyl, phenyl, carboxy or C4_4 alkoxycarbonyl group and with a hydroxy group, and in the groups - cycloalkyleneimino mentioned above a methylene group contiguous to the nitrogen atom can be replaced by a carbonyl group, with a C? _3 alkyl group, which is substituted with a cycloalkyleneimino group of 5 to 7 members, being condensed to the cycloalkyleneimino groups of 5 to 7 members mentioned above, through 2 contiguous carbon atoms, a phenyl group optionally mono- or di-us titino with fluorine, chlorine or bromine atoms, with methyl or methoxy groups, -. the substituents being the same or different, or a pyrazine or thiazole group optionally substituted with an amino group, wherein the above-mentioned monosubstituted phenyl groups, with a fluorine, chlorine or bromine atom, can also be substituted with a a methyl, methoxy or nitro group, a pyridyl group, optionally substituted with a chlorine or bromine atom or with a methyl group, an oxazolyl, isoxazolyl, imidazolyl or thiazolyl group optionally substituted with a methyl group, to which a ring of phenyl through 2 contiguous carbon atoms, R5 means a hydrogen atom or a C3_3 alkyl group, especially those compounds of the general formula I, in which Ri to R3 and R5 are defined as mentioned above and R4 means a hydrogen atom, a C6_6 alkyl group or a C5_7 cycloalkyl group, optionally substituted with a C3_3 alkyl group, wherein a methylene group in the position 3 or 4, referred to the carbon atom of the group R 3 -C (R 4 NR 5) =, may be replaced by an imino group optionally substituted with a C 1 -C 3 alkyl group, a phenyl or naphthyl group, which may be substituted with a fluorine, chlorine, bromine or iodine, with a C? -3 alkoxy group, amino, C C-3-amino alkyl, di- (C 1-3 alkyl) -amino, C 2 -5-amino alkanoyl, N- (C C alkyl) 3) -amino-a1-canoi-1-C2_5-amino, alkyl-C5-5-its 1-amino-1-ony, N- (C1-3-alkyl) -alkyl-C5-s, or 1-amino-1, eul f oni 1 ami no or N- (C1-3 alkyl) -f on i 1 su 1 f oni 1 amino, or with a C ?3 alkyl group which may be substituted with an alkyl C ?5-amino group, di - (alkyl C? _5) -ami, non-1-tho ring, 1-oxide-thiomorpholino, 1,1-dioxide-thiomorpholino, piperazino, N- (alkyl C? _3) - p ip e ra zi no, N -phenyl-piperazino, cycloalkyl 1 in Cs-7-imino or with a group ci c 1 oal qui 1 in C4-.7-im.ino, where the groups ci c 1 or 1 quil in C5-7 , -imino previously mentions two may be substituted with one or two C1-3 alkyl groups, with a C5-7 cycloalkyl or phenylaryl group, with a C3_3 alkyl group, C5_7 cycloalkyl, or phenyl, carboxy or C1-4 alkoxy-ca rboni 1 oy with a hydroxy group, its isomers and its salts. Particularly preferred compounds of the general formula I are those in which Ri to R5 are defined as mentioned above and R2 is in the 5-position, in particular those compounds in which X means an oxygen atom, Ri means an atom of hydrogen, R 2 means an aminocarbonyl group in the 5-position, R 3 signifies a hydrogen atom or a C 4 -4 alkyl group which in terminal position can be substituted with a chlorine or bromine atom or with a phenylsulfonyl group, R means an atom of hydrogen, a C3_3 alkyl group or a cyclopentyl or cyclohexyl group optionally substituted with a methyl group, wherein in the cyclohexyl group a methylene group in the 4-position, referred to the carbon atom of the group R3-C (R4NR5) =, may be replaced by an imino group, optionally substituted with a methyl group, a phenyl group, which may be substituted with a fluorine, chlorine, bromine or iodine atom, with a methyl group; or ethyl, which in each case is substituted by a C 1 _ 3-amino alkyl group, di- (C 1 -C 3 alkyl) -amino, thio orno rfo 1 i no, 1-oxide-t i omor fo 1 ino, 1, 1-di-oxide-thio-rhenoxy, N-phenyl-piperazino, cycloalkyl, queni 1 enimi not of 5 to 6 members or with a cycloalkyleneimino group of 5 to 7 members, the 5 to 7 membered cycloalkyleneimino groups mentioned above having one or two methyl groups, with a cyclohexyl or phenyl group, with a methyl, cyclohexyl or phenyl group, and with a hydroxy group, or with a methyl or ethyl group may be substituted. , which may be substituted in each case with a phenyl group which is substituted with a cycloalkyleneimino group of 5 to 7 members, being condensed to the aforementioned cycloalkyleneimino groups, through 2 contiguous carbon atoms, additionally a phenyl ring, with a methyl or ethyl group, which is substituted with an amino, methylamino or ethylamino group which, in each case, is additionally substituted at the nitrogen atom of the amine with a benzyl or phenylethyl group, the monocarboxylic part may be substituted phenyl of the above-mentioned groups in each case with a fluorine, chlorine or bromine atom, with a methyl, methoxy, cyano, trifluoromethyl or nitro group, or di-ot RI-substituted with fluorine, chlorine or bromine atoms, with methyl or methoxy groups, and the substituents may be the same or different, wherein additionally the aforementioned phenyl groups may be substituted with a fluorine, chlorine or bromine atom, with a methyl, methoxy or nitro group, and R5 means a hydrogen atom or a C1-4 alkyl group, their isomers and their salts. Compounds of the general formula I which are very particularly preferred are those in which X is an oxygen atom, Ri is a hydrogen atom, R 2 is an aminocarbonyl group in the 5-position, R 3 is a hydrogen atom or a C-alkyl group. -, R4 means a phenyl group which may be substituted with a fluorine, chlorine, bromine or iodine atom, with a methyl or ethyl group, which in each case is substituted with a C3_3-amino alkyl group, di- (alkyl) C? _3) -amino, 1-ring, 1-oxide-ti-omor-olino, 1, 1 -diox ido-ti orno rfo 1 ino, N-f eni 1 -p ipe razi no, ci cl oal queni 1 en imi no de 5 a 6 -members or with a cycloalkyleneimino group of 5 to 7 members, the cycloalkyleneimino groups of 5 to 7 members mentioned above having one or two methyl groups, with a cyclohexyl or phenyl group, with a methyl, cyclohexyl or phenyl group, and with a hydroxy group, or with a methyl group may be substituted. or ethyl, which may be substituted in each case with a phenyl group which is substituted at the 4-position with a cycloalkyleneimino group of to 7 members, being condensed to the aforementioned cycloalkyleneimino groups, through 2 contiguous carbon atoms, additionally a phenyl ring, with a methyl or ethyl group, which are substituted with an amino, methylamino or ethylamino group that in each case furthermore, it is substituted at the nitrogen atom of the amine with a benzyl group, and in which the phenyl part can be mono-unsubstituted with a fluorine, chlorine or bromine atom, with a methyl, methoxy group , cyano, trifluoromethyl or nitro, or disubstituted with methyl or methoxy groups or trisubstituted with methyl or methoxy groups, and the substituents may be the same or different, wherein additionally the aforementioned mono-substituted phenyl groups may be substituted with a fluorine, chlorine or bromine, with a methyl, methoxy or nitro group, and R5 means a hydrogen atom or a C4_4 alkyl group, their isomers and their salts. As particularly preferred compounds there may be mentioned, for example, the following: (a) 3-Z - [1- (4-piperidinomethyl-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone, (b) 3-Z- [1- (4-bromo-f-enylamino) -1-methyl-methylene] -5-amido-2-indolinone, (c) 3-Z- [1- (4-piperidinomethyl-phenylamino) -1 -butyl-methylene] -5-amido-2-indolinone, (d) 3 - Z - [1 - (4-chloro-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone, (e) 3-Z- (1-phenylamino-methylene] -5-amido-2-indolinone, (f) 3-Z- [1- (4- (N-benzyl-N-methyl-aminomethyl) -phenylamino) -1- methyl-methylene] -5-amido-2-indo-1-inone, (g) 3-Z- [l- (4- (N- (4-chlorobenzyl) -aminomethyl) -phenylamino) -1-methyl-methylene] - 5-amido-2-indolinone, (h) 3-Z- [1- (4- (N-benzyl-N-ethyl-aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone , '(i) 3-Z- [l- (4- (N-benzyl-aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone, (j) 3-Z- [1 - (- (N-benzyl-N-methyl-aminomethyl) -phenylamino) -methylene] -5-amido-2-indolinone, (k) 3-Z- [1- (4- (2,3,4 , 5-tetrahydro-benzo (d) azepin-3-yl-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone, (1) 3-Z- [1- (4-piperidinomethyl) -3-nitro-f-en-1-amino) -1-methyl-1-methyl-1-in-5-ami-do-2-indo-1-inone and (m) 3-Z- [1- (4-methyl-3 -nitro-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone, as well as its isomers and its salts. According to the invention, the novel compounds are obtained, for example, according to the following methods known in principle from the literature: a. Reaction of a compound of the general formula wherein X and R3 are defined as mentioned at 1 comi at zo, R2 'possesses the meanings mentioned at the beginning for R2, R6 signifies a hydrogen atom or a protective group for the nitrogen atom of the lactam group, being able to represent one of the radicals R2 'or R6 also a bond to a solid phase optionally formed through a spacer, and the radicals R2' or Re have the meanings mentioned above, and Zi, means a halogen atom, a hydroxy group , alkoxy or aralkoxy, for example a chlorine or bromine atom, a methoxy, ethoxy or benzyloxy group, or with an amine of the general formula wherein R 4, and R 5 are defined as mentioned at the beginning, and, if necessary, subsequent removal of a protecting group used for the nitrogen atom of the lactam group or a solid phase. As a protective group for the nitrogen atom of the lactam group, for example, an acetyl, benzoyl, ethoxycarbonyl, tert-butoxycarbonyl or benzyloxycarbonyl group may be used., and as a solid phase, a resin such as a resin of 4- (2 ', 4'-dimethoxy-phenyl-1-amino-1-phenoxy) is suitably carried out via the amino group, or a p -benzyl-1-oxybenzyl alcohol, the bond being conveniently effected through an intermediate member, such as a derivative of 2,5-dimethoxy-4-hydroxy-1-b in cyclohexane. The reaction is carried out suitably in a solvent such as dimethylformamide, toluene, acetonitrile, tetrahydrofuran, dimethisulfoxide, methylene chloride or mixtures thereof, optionally in the presence of an inert base such as triethylamine, N-ethyl-di-opi op 1 amine or sodium hydrogen peroxide, at temperatures between 20 and 175 ° C, and a protective group used can be separated at the same time as a consequence of a triamine. If Zi in a compound of the general formula II means a halogen atom, then the reaction is preferably carried out in the presence of an inert base at temperatures between 20 and 120 ° C. If Zi in a compound of the general formula II means a hydroxy, alkoxy or aralkoxy group, then the reaction is preferably carried out at temperatures between 20 and 200 ° C. The subsequent separation, if necessary, of a protecting group used is conveniently carried out by hydrolysis in an aqueous or alcoholic solvent, for example in methanol / water, ethanol / water, isopropanol / water, tetr abidr or fur ano / water, dioxane / water, dimethylformamide / water, methanol or ethanol in the presence of an alkaline 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 shaking with an organic base such as ammonia, methylamine, butylamine, dimethylamine or piperidine in a solvent such as methanol, ethanol, dimethylformamide or mixtures thereof or in an excess of the amine employed at temperatures between 0 and 100 ° C, preferably at temperatures between 10 and 50 ° C. The separation of a solid phase used is preferably carried out by trifluoroacetic acid and water at temperatures between 0 and 35 ° C, preferably at room temperature. b. For the preparation of a compound of the general formula I, in which R2 represents one of the aminocarbonyl groups mentioned at the beginning: amidation of a compound of the general formula wherein Ri and R3 to R5 are defined as mentioned at the beginning, or their reactive derivatives, with an amine of the general formula H - (R7NR8) (V), wherein R7 and Ra, which may be the same or different, they mean hydrogen atoms or groups at 1 qui what C? -3. The amidation is preferably carried out in a solvent such as methylene chloride, diethyl ether, tetrahydrofuran, toluene, dioxane, acetonitrile, dimethisulfoxide or dimethyl ester, optionally in the presence of an inorganic base or a tertiary organic base, preferably at temperatures between 20 ° C and the boiling temperature of the solvent used. In this case, the amidation is carried out with a corresponding acid, preferably in the presence of a water subtracting agent, for example in the presence of isobutyl ester of chloric or ferric acid, tetraethylic acid ester or rt or carbon, ester trimethylate of orthoacetic acid, 2, 2 -dime t oxyp clothing, tetr ame t oxi si 1 year, thionyl chloride, triamote 1 c 1 oros ilium, phosphorus trichloride, phosphorus pentoxide, "N, N '- dicyclohexylcarbodiimide, N, N'-dicyclohexylcarbo-diimide / N-hydroxysuccinimide,, N '-di-cyclohexyl-carbo-diimide / 1-hydroxy-benzotriazole, tetrafluoroborate of 2- (lH-ben zotriazo 1 - 1 - i 1) - 1, 1, 3, 3 - tetr amethyluronium, 2- (lH-benzotriazol-1-yl) -1, 1,3,3-tetra-methyluronium / l-hi-dr oxy -benzotriazl tetrafluoroborate, N, N'-ca rboni Idi imida zo 1 otrif enilfo sf ina / tet carbon fi broideuro, and eventually with the addition of a base such as pyridine, 4-dimetre i laminop ir idina, N -me ti 1 -mor fo 1 or triethylamine, conveniently at temperatures between 0 and 150 ° C, preferably at temperatures between 0 and 100 ° C, and the acylation is carried out with a corresponding reactive compound such as their anhydrides, esters, imidazolides or halides, optionally in the presence of a tertiary organic base such as triethylamine, N-ethyldiisopropylamine or N-methyl-1-amino-1, at temperatures between 0 and 150 ° C, preferably at temperatures between 50 and 100 ° C. If, according to the invention, a compound of the general formula I, which contains an alkoxycarbonyl group, is obtained, it can be converted, by hydrolysis, into a compound of the general formula I, which contains an amino or alkylamino group, it can then be converted, by alkylation or reductive alkylation, into a corresponding alkylamino or dialkylamino compound, or a compound of the general formula I, which contains an amino or alkylamino group, then it can be converted, by acylation, into a corresponding composed of acyl, or a compound of the general formula I, which contains a carboxy group, then it can be transformed, by esterification or amidation, into a corresponding ester or aminocarbonyl compound, or a compound of the general formula I, which contains a nitro group, then it can be transformed, by reduction, into a corresponding amino compound. The subsequent hydrolysis is preferably carried out in an aqueous solvent, for example in water, isopropanol / water, tetrahydrofuran or water or dioxane / water, in the presence of an acid such as trifluoroacetic acid, hydrochloric acid or sulfuric acid, or presence of an alkaline base such as lithium hydroxide, sodium hydroxide or potassium hydroxide, at temperatures between 0 and 100 ° C, preferably at temperatures between 10 and 50 ° C.

The subsequent reductive alkylation is preferably carried out in a suitable solvent such as methanol, methanol / water, toluene / 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, for example hydrogen in the presence of Raney nickel, platinum or pa 1 adi or carbon, or in the presence of a metal hydride such as sodium borohydride., lithium borohydride or lithium aluminum hydride, at temperatures between 0 and 100 ° C, preferably at temperatures between 20 and 80 ° C. The subsequent alkylation is carried out with an alkylating agent such as an alkyl halide or dialkyl sulfate such as methyl iodide, dimethyl sulfate or propyl bromide, preferably in a solvent such as methanol, ethanol methylene chloride, tetrahydrofuran, toluene, dioxane, dimethylsulfoxide or dimethylformamide, optionally in the presence of an inorganic base or a tertiary organic base such as thiaminide, ethi 1 di s op r op i 1 amine or dimethylaminopyridine, preferably at temperatures between 20 ° C and the boiling temperature of the solvent used. The subsequent acylation 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 base or a tertiary organic base, preferably at temperatures between 20 and 20. ° C and the boiling temperature of the solvent used in this case, the acylation is carried out correspondingly acid preferably in the presence of a water subtracting agent, for example in the presence of isobutyl ester of c 1 or orbital acid, ester , tetraethylic acid or to carbonic acid, trimethylic orthoacetic acid ester, 2, 2 -dime t ox ip r opane, tet rax ime toxi 1 anus, thionyl chloride, t rime ti 1 c l urans ilane, phosphorus trichloride, pentoxide of phosphorus, N, N'-dicycloxycarbodiimide, N, N '-di c 1 ohex i 1 ca rbo -di imide / N-hydroxysuccinimide, N, N' -di-cyclohexyl-carbodiimide / 1-hydroxybenzotr iazole, 2 - (lH-benzo triazol-1-yl) -1, 13, 3 -tetr amethylamine, tetrafluoroborate 2 - (lH-benzo triazol-1-yl) -1, 13, 3-tetr ame ti 1 ur oni o, te tra fluo ra to 2- (lH-benz otr ia z ol - 1 - i 1) - 1, 1, 3, 3 - tetr ame ti 1 ur on io, / ll-hydroxy-benz otria zol,, - carboni 1 di imi da zo 1 otrif eni 1 fosfi na / tetr acl carbon monoxide, and optionally with the addition of a base such as poridine, 4-d-ime-thi-1-ai-pyridine, N -methyl-1-amino-1-or triethylamine, conveniently at a temperature between 0 and 150 ° C, preferably at temperatures between 0 and 100 ° C and the acylation is carried out with a corresponding reactive compound such as its anhydrides, esters, imidazolides or halides, optionally in the presence of a tertiary organic base such as tiethylamine, N-ethyl-di is op r opol amine or N-me ti 1 -mo r fo 1 ina, at temperatures between 0 and 150 ° C, preferably at temperatures between 50 and 100 ° C. Subsequent esterification or amidation is conveniently carried out by reaction of a corresponding carboxylic acid derivative reactive with a corresponding alcohol or amine, as described above. The subsequent reduction of a nitro group is preferably effected by hydrogenolysis, for example with hydrogen in the presence of a catalyst, such as palladium / carbon or Raney nickel, in a solvent such as methanol, ethanol, acetic acid ethyl ester, dimethylformamide dimethyl- f or rmami da ce to ona or glacial acetic acid, possibly under the addition of an acid such as hydrochloric acid or glacial acetic acid, at temperatures between 0 and 50 ° C, but preferably at room temperature, and at a hydrogen pressure from 1 to 7 bars, but preferably from 3 to 5 bars. In the case of the reactions described above, optionally present reactive groups such as carboxy, amino, alkylamino or imino groups can be protected during the reaction by customary protective groups which, after the reaction, are separated again. For example, as the protective radical for a carboxyl group, the triethyl group, methyl, ethyl, tert-butyl, benzyl or tetrahydropyranyl, and as a protective radical for an amino group can be considered., alkylamino or imino comes into consideration the acetyl group, trifluoroacetate, benzoyl, ethoxycarbonyl, tert -butoxycarbonyl, benzyloxycarbonyl, benzyl, methoxybenzyl or 2,4-dimethyl-t-oxybenzyl and, for the amino group, additionally the phthalyl group.

The eventual separation of a used protective radical is carried out, for example, by hydrolysis in an aqueous solvent, for example in water, isopropanol / water, water / water / 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 alkaline 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 separation of a benzyl, methoxybenzyl or benzyloxycarbonyl radical is, however, effected, for example, by hydrogenolysis, for example with hydrogen in the presence of a catalyst such as a carbon dioxide, in a solvent such as methanol, ethanol, ethyl ester of acetic acid, dimethylformamide, dimethylaminophenone or glacial acetic acid, optionally with the addition of an acid such as hydrochloric acid or acetic acid, optionally glacial with the addition of an acid such as acid hydrochloric acid 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 3 to 5 bar. The separation of a methoxybenzyl group can also be carried out in the presence of an oxidizing agent such as cerium (IV) ammonium nitrate in a solvent such as methylene chloride, acetonitrile or acetonitrile or water, at temperatures between 0 and 50 ° C, but preferably at room temperature. The separation of a 2,4-dimethoxy cyclic radical is, however, preferably carried out in trifluoroacetic acid in the presence of anisole. The separation of a tert-butyl radical or tert -buyl-1-oxycarbonyl is preferably effected by treatment with an acid such as trifluoroacetic acid or hydrochloric acid, optionally with the use of a solvent such as methylene chloride, dioxane, acetate of ethyl or ether. The separation 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, at temperatures between 20 and 50 ° C.

Furthermore, chiral compounds of the general formula I obtained can be separated into their enantiomers and / or diastereoisomers. _ _Asi, for example, The compounds of the formula generaj. I 'got do,' - what I know ... man i f i_es t an - .. in race atqs ,. __HE. In the case of known methods (see Allinger NL and Eliel EL in "Topics in Stereochemistry", Vol 6, Wiley Internship, 1971), in their optical antipodes, and compounds of the general formula I with less 2 asymmetric carbon atoms can be separated, by virtue of their physiological differences, according to methods known per se, for example by chromatography and / or fractional crystallization, in their diastereoisomers which, if they result in racemic form, they can then be separated into the enantiomers as mentioned above. The separation into the enantiomers is preferably effected by column separation in chiral phases or by recrystallization in an optically active solvent or by reaction with an optically active substance which forms with the racemic compound salts or derivatives such as, for example, esters or amides, in particular acids and their activated derivatives or alcohols, and separation of the mixture of salts of asteroid salts obtained in this way, for example by virtue of different solubilities, being able to be liberated from the pure diamine salts or derivatives Free antipodes by the action of appropriate agents. Particularly customary optically active acids are, for example, the D and L forms of tartaric acid, dibenzoate, aric acid, di-o-tolyltartaric acid, malic acid, cid-maleate, and canarian acid. ul f óni co, glutamic acid, N- a ca t i lglu tamic acid, aspartic acid, N-acetyl aspartic acid or quinaic acid. As optically active alcohol, for example, (+) - or (-) - menthol is considered, and as an optically active acyl radical in midas, for example, the radical (+) - or (-) - menthyloxycarbonyl is suitable. Furthermore, the compounds of the formula I obtained can be converted into their salts, in particular for the pharmaceutical application in their physiologically compatible salts with inorganic or organic acids. Suitable acids include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid, maleic acid or methanesulfonic acid. In addition, the novel compounds of formula I, thus obtained, if they contain a carboxy group, can then be converted, if desired, into their inorganic or organic salts or organic acids. , in order to re-apply the effective application of its physiologically compatible salts, as bases, in this case, under consideration, for example, sodium hydroxide. , potassium hydroxide, cyclohexylamine, ethanolamine, diethanolamine and triethanolamine The compounds of the general formulas I to V used as starting materials are known in part from the literature or are obtained according to methods known from the literature or In the examples, as already mentioned at the beginning, the new compounds of the general formula I, in which Ri represents a hydrogen atom or a prodrug radical, have valuable pharmacological properties, in particular inhibitory effects on di different kinases and cyclic complexes na / CDK, on the proliferation of cultured human tumor cells, as well as after oral administration on the growth of tumors in mice deprived of the immune system that had been infested with human tumor cells. For example, the compounds collected in Table 1 were examined for their biological properties as follows: Assay 1 Inhibition of cyclin / CDK enzymatic activity in vitro HFive® insect cells (BT I-TN-5 B 1-4 active human cyclin / CDK) using a Baculovirus vector containing two promoters (promoter polyhedrin enhancer, PÍO enhancer promoter) GST-labeled cyclins (for example cyclin DI or cyclin D3) with the corresponding His6-labeled CDK subunit (for example for CDK4 or CDK6) were expressed in the same cell.The active holoenzyme was isolated by affinity chromatography on glutamate on S epha rose.pRB labeled with recombinant GST (amino acids (aa) 379-928) was produced in E. coli and purified by affinity chromatography on glutta on-S epha rose.

The substrates that were used for the kinase assays were dependent on the specific kinases. Histone Hl (Sigma) was used as substrate for cyclin E / CDK2, cyclin A / CDK2, cyclin B / CDK1 and for v-cic 1 ina / C DK 6. pRB labeled with GST (aa 379-928) was used as substrate for cyclin D1 / CDK4, cyclin D3 / CDK4, cyclin D1 / CDK6 and for cyclin D3 / CDK6. Lysates from insect cells infested with Baculovirus re combine also recombinant kinases (obtained from lysates by purification) were incubated for 45 minutes at 30 ° C together with radiolabeled ATP in the presence of a suitable substrate with different concentrations of the inhibitor in a 1% solution of DMSO (dimethylsulfoxide). Proteins substrates with associated radioactivity were precipitated with TCA (trichloroacetic acid) at 5% in plates from my cropping of multiple hydrophobic PVDF wells (Millipore) or with 0.5% phosphoric acid solution on Whatman P81 filters. . After the addition of scintillation fluid, the radioactivity was measured in a Wallace 1450 Microbeta liquid scintillation counter. Double measurements were carried out for each concentration of the substance; Cl 50 values were calculated for the inhibition in z ima tica Assay 2 Inhibition of the proliferation of cultured human tumor cells Cells from the tumor cell line of 1 i or i osarcup SK-UT-1B (obtained from the American Type Culture Collection (ATCC)) were cultured in minimal essential media with non-essential amino acids (Gibco), supplemented with sodium pyruvate (1 mmol), glutamine (2 mmol) and 10% fetal bovine serum (Gibco) and harvested in the logarithmic growth phase. Next, SK-UT-1B cells were incorporated into Cytostar® multi-well plates (Amersham) with a density of 4000 cells per well and incubated overn in an incubator. A Different concentrations of the compounds were added to the cells (dissolved in DMSO, final concentration: <1%). After 48 hours of incubation, 14C-thymidine (Amersham) was added to each well and incubated for a further 24 hours. The amount of 4C-thymidine, which was incorporated into the tumor cells in the presence of the inhibitor and representing the number of cells in the S phase, was measured in a Wallace 1450 Microbeta liquid scintillation counter. IC 50 values were calculated for the inhibition of proliferation (= inhibition of incorporated 14 C-thymidine) -under correction of background radiation. All measurements were made in duplicate.

Test 3 In vivo effects in mice deprived of the tumor-bearing immune system 106 cells [SK-UT-1B or non-small cell lung tumor NC I -H 460 - (ATCC ob t ents)] were injected subcutaneously into a volume of 0.1 ml in male and / or female mice deprived of the immune system (NMRI nu / nu; 25-35 g; N = 10-20); alternatively, small pieces of conglomerates of SK-UT-1B or NCI-H460 cells were subcutaneously implanted. One to three weeks after the injection or implantation, a kinase inhibitor was applied orally daily for 2 to 4 weeks (by gastric tube). The size of the tumor was measured three times per week with a digital caliper. The effect of a kinase inhibitor on tumor development was determined as percentage of inhibition compared to a control group treated with placebo. The following table contains the results found from Test 2 in vitro: By virtue of their biological properties, the new compounds of the general formula I, their isomers and their physiologically compatible salts are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation.

To diseases of this type belong (without pretensions of totality): viral infections (for example HIV and sarcoma, kaposi); inflammation and autoimmune diseases (eg colitis, arthritis, Alzheimer's disease, glomerulonephritis and wound healing); bacterial, fungal and / or parasitic infections; leukemias, lymphoma and solid tumors; skin diseases (for example psoriasis); Bone diseases; cardiovascular diseases (for example restenosis and hypertrophy). In addition, they are useful as protection for proliferating cells (for example, hair cells, intestine, blood and progeny), against DNA damage by radiation, UV treatment and / or cytostatic treatment. The new compounds can be used for short-term or long-term treatment of the abovementioned diseases, also optionally in combination with other compounds of the "prior art" as well as the other cytostatics. The dosage necessary to achieve a corresponding effect is conveniently, in the case of intravenous administration, at 0.1 to 30 mg / kg, prefey at 0.3 to 10 mg / kg and, in the case of oral administration, at 0, 1 to 100 mg / kg, prefey at 0.3 to 30 mg / kg, in each case 1 to 4 times a day. For this, the compounds of the formula I prepared according to the invention can be incorporated into conventional galenic preparations such as tablets, dragees, capsules, powders, suspensions, suppositories or in the form of solutions for injections or infusions, optionally in combination with other active substances, together with one or more support substances and / or agents customary inert diluents, for example with 1 to 1 ml of maize, lactose, sucrose, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water / ethanol, water / water, water or water, polyethylene glycol 1, propylene glycol, alcohol ceti 1 es-teari 1 i co, carboxymethylcellulose or substances with a fat content, such as hard fat or their suitable mixtures. The following examples have to explain the invention in more detail: EXAMPLE I 1-Acetyl-2-indolinone-5-carboxylic acid methyl ester 10.5 g of 2-indole inona-5-c arboxylic acid methyl ester (preparation analogous to Ogawa, Hidenori et al. Chem. Pharm. Bull 36, 2253-2258 (1988)) are stirred for 4 hours at 140 ° C in 30 ml of acet anhydride. Then it is left to cool, poured on ice / water and the precipitate is filtered with suction. The product is washed again with water, then it is taken up in methylene chloride, dried over sodium sulfate and concentrated. Yield: 11 g (86% of theory), Rf value: 0.63 (silica gel, methylene chloride / methanol = 50: 1).

EXAMPLE II 1-Acetyl-3 - (1-ethoxy-1-butyl-methyl-2-yl) -2-indolinone-5-carboxylic acid methyl ester 11 g of 1-acetyl-2-indole-1-methyl ester 5-Carboxylic acid is stirred for 2 hours at 100 ° C in 110 ml of acetonitrile and 30 ml of triethyl ester of o-t-valerate. It is then concentrated by rotary evaporation and the residue is washed with ether and filtered with suction.

Yield: 11.5 g (67% of theory), Rf value: 0.55 (silica gel, methylene chloride 1 ene / e te r, pe t r o l eo / a ce t a t o ethyl = 4: 5: 1). Analogously to Example II, the following compounds are prepared: (1) 1-Acetyl-3- (1-ethoxy-methylene) -2-indolinone-5-carboxylic acid methyl ester Prepared from 1-methyl-1-methyl ester ace t il -2 -indolinone- 5 -ca rboxyl ico and ester trimethyl of orthophoric acid. (2) 1-Acet yl-3 - (1-ethoxy-l-methyl-methylene) -2-indolinone-5-carboxylic acid methyl ester Prepared from methyl ester of 1-a ce t il-2 acid - indolinone - 5 - ca rboxi 1 i co and orthoacetic acid triethyl ester. (3) 1-Ace t il-3 - (1-ethoxy-1-ethyl-methylene) -2-indolinone-5-carboxylic acid methyl ester Prepared from methyl ester of 1-a ce t il-2 acid - indole inona- 5 - ca rboxi 1 i co and triethyl ester of ortho op op op ico ico.

E n gle III 28.0 g of Rink resin (resin MBHA, firm Novobiochem) are allowed to swell at 330 < nl of dimethylformamide. Next, 330 ml of 30% piperidine in dimethylformamide is added and shaken for 7 minutes in order to separate the 9H-f-1-en-9-yl-t-oxy-carbonyl group. The resin is then washed several times with dimethylformamide. Finally, 7.3 g of 2-indo-1-inona-5-caboxboxylic acid (preparation analogously to Ogawa, Hidenori et al., Chem. Pharm. Bull., 36, 2253-2258 (1988)), are added. , 6 g of hydroxybenzotriazole, 13.3 g of O- (benzotriazol-1-yl) -N, N, ', N' -te-tramethyl-uronium tetrafluoroborate and 5.7 ml of - eti 1-di is op r op i 1 amine in 300 ml of dimethylformamide and shaken for 1 hour. Then, the solution is filtered with suction and the resin is washed five times with 300 ml of dimethylformamide and three times with 300 ml of methylene chloride. For drying, nitrogen is blown through the resin. Yield: 20 g of charged resin.

Example IV 0.4 g of the charged resin, prepared according to Example III, is stirred with 2.5 ml of anhydride at 90 ° C for 1 hour. Then 2.5 ml of trimethyl ester of orthovaleric acid are added and shaken for another 3 hours at 110 ° C. The resin is then filtered off with suction and washed with dimethylformamide, methanol and, finally, with methylene chloride. Yield: 0.6 g of wet resin. Analogously to Example IV, the following charged resins are prepared: (1) Resin charged with 3-Z- (1-ethoxy-methyl-1-in) -5-ami-do-2-indole-inone, by reaction of the product of the Example I and triethyl ester of orthophoric acid. (2) Resin charged with 3-Z - (1-methyl t-oxy-1-methylmethylene) -5-amido-2-indolinone, by reaction of the product of Example I and trimethylic orthoacetic acid ester. (3) Resin charged with 3-Z- (1-methyl t-oxy-1-ethyl-1-yl-1-en-5-ami-do-2-indo-1-a-a), by reaction of the product of Example I and trimethyl ester of acid or op op opon ion co. (4) Resin charged with 3-Z- (1-methyl t-i-1-pr or i-methyl-1-en-5-amido-2-indolone), by reaction of the product of Example I and trimethyl ester of acid or tobut iri co. (5) Resin charged with 3-Z- (1 -me t oxy-1 -et enylmethylene) -5-amido-2-indolinone, by reaction of the product of Example I and 3,3,3-triethoxyprop-1- eno (6) Resin charged with 3-Z - (2 - 1 -me t ox i-1 - (3-bromo-propyl) -methylene) -5-amido-2-indolinone, by reaction of the product of Example I and ester Trimetilic acid 4-boron -or t obu t irico. (7) Resin charged with 3-Z- (1-methyl t-oxy-1- (2-phenylsulphonylethyl) -methylene) -5-amido-2-indolinone, by reaction of the product of Example I and triethyl 3-methyl ester f ni 1 - s ul f oni 1 - or t op r op i on i co.

EXAMPLE V 4- (Neil-aminometryl) -notrobenzene 6 g of 4-bromide bromide are dissolved in 25 ml of ethanol, mixed with 25 ml of 10% ethanolic ethylamine solution and boiled. reflux for 2 hours. The solution is then concentrated by rotary evaporation, the residue is taken up in methylene chloride and washed with dilute sodium hydroxide solution. Finally, the organic phase is concentrated. Yield: 2.3 g (46% of theory), Rf value: O, 20 (silica gel, methylene chloride / methanol = 9: 1).

Analogously to Example V, the following compounds are prepared: 4- [N- (4-chlorophenyl-methyl) -aminomethyl] -nitrobenzene 4- N -cyclohexyl-aminomethyl) -nitrobenzene 4- N -isopropyl-aminomethyl) -nitrobenzene 4- N-butyl-aminomethyl) -nitrobenzene 4- N-methoxycarbonylmethyl-aminomethyl) -ni tr ob ene en o 4- N-benzyl-aminomethyl) -nitrobenzene 4-pyrrolidino-methyl) -nitrobenzene morpholino-methyl) -nitrobenzene 4- piperidino -methyl) -nitrobenzene 4- hexamethyleneimino-methyl) -nitrobenzene 4- 4-hydroxy-piperidino-methyl) -nitrobenzene 4- 4-methyl-piperidino-methyl) -nitrobenzene 4- 4-ethyl-piperidino-methyl ) -nitrobenzene 4- 4-isopropyl-piperidino-methyl) -nitrobenzene 4- 4-phenyl-piperidino-methyl) -nitrobenzene 4- 4-benzyl-piperidino-methyl) -nitrobenzene 4- 4-ethoxycarbonyl-piperidino-methyl) - nitrobenzene 4-dimethylamino-methyl) -nitrobenzene di-n-propylamino-methyl) -nitrobenzene 4- (4-tert.-butexcarbonyl-piperazino-methyl) -nitrobenzene 4- (dimethylamino-methyl) -nitrobenzene 2-diethylamino-ethyl) -nitrobenzene 4- 2-morphino-ethyl) -nitrobenzene 4- 2 -pyrrolidino-ethyl) -nitrobenzene 4- 2-piperidino-ethyl) -nitrobenzene 4- N -ethyl-N-benzyl-aminomethyl) -nitrobenzene 4- Nn-propyl-N-benzyl-aminomethyl) -nitrobenzene N-met il-N- (_4 -chloro-enylmethyl) -aminome ti-1-nitrobenzene 4- N -methyl-N- (4-bromophenylmethyl) -aminomethyl-nitrobenzene - [N-methyl-N- (3-chlorofenylmethyl) -aminomethyl-nitrobenzene 4- N-methyl-N- (3, 4-dimethoxyphenylmethyl) -amomethyl-nitrobenzene N-methyl-N-14-methoxy-enylmethyl) -aammiinnoommee tt ii 1l] -ni tr-benzene 4- N- (2,2,2-trifluorostil) -N-benzyl- a i nome til -ni tr obenceno 4- [N- (2,2,2-trifluoroethyl) -N- (4-chlorophenylmethyl) -aminomethyl] -nitrobenzene 4- (2,6-dimethyl-piperidino-methyl) -nitrobenzene 4- (thiomorpholino-methyl) -nitrobenzene 4- (S-oxide-thiomorpholino-methyl) -nitrobenzene 4- (S, S-dioxido-thiomorpholino-methyl) -nitrobenzene 4- (azetidino-methyl) -nitrotencene 4- (2 , 5-dihydropyrrol-l-yl-methyl) -nitrobenzene 4- (3,6-dihydro-2H-pyridin-1-yl-methyl) -nitrobenzene 4- (2-methoxycarbonyl-pyrrolidino-methyl) -nitrobenzene 4- ( 3, 5-dimethyl-piperidino-methyl) -nitrobenzene 4- (4-phenyl-pipe-in-l-methyl) -nitrobenzene 4- (4-phenyl-4-hydroxy-piperidino-methyl) -nitrobenzene 4- [N- (3, 4, 5-trimethoxy-benzyl) -N-methyl-ami nome ti 1] -ni tr-benzene 4- [N- (3,4-dimethoxy-benzyl) -N-ethyl-aminomethyl] -nitrobenzene 4- [N- (3-chlorobenzyl) -N-methyl-aminomethyl] -nitrobenzene 4- [N- (2,6-dichlorobenzyl) -N-methyl-aminomethyl] -nitrobenzene 4- [N- (4-trifluoromethylbenzyl) -N-methyl-aminomethyl] -nitrobenzene 4- (N-benzyl-N) -isopropyl-aminomethyl) -nitrobenzene 4- (N-benzyl-N-tert-butyl-aminomethyl) -nit r or 4- (diisopropylamino-methyl) -nitrobenzene 4- (di-n-propylamino-methyl) -nitrobenzene 4 - (diisobutylamino-methyl) -nitrobenzene 4- (2, 3, 4, 5-tetrahydro-benzo (d) azepin-3-ylmethyl) -nitrobenzene 4- (2,3-dihydro-isoindol-2-yl-methyl) ) -nitrobenzene 4- (6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinolin-2-ylmethyl) -5-nitrobenzene 4- (1, 2, 3, 4-tetrahydro-isoquinoline-2) -yl-methyl) -nitrobenzene 4- [N- (2-hydroxyethyl) -N-benzyl-aminomethyl] nor tr-benzene 4- [N- (1-ethyl-pentyl) -N- (pyridin-2-yl-methyl ) - aminometil] -nitrobenzene 4- (N-phenethyl-N-methyl-aminomethyl) -nitrobenzene 4- [N- (3,4-dihydroxy-phenethyl) -N-methyl-aminomethyl] -nitrobenzene 4- [N- (3, 4, 5-trimethoxy-phenethyl) -N-methyl-aminomethyl] -nitrobenzene 4- [N- (3,4-dimethoxy i-phenethyl) -N-methyl-aminome ti 1] -nitr-benzene 4- [N- (4-nitro-phenethyl) -N-methyl-aminomethyl] -nitrobenzene 4- (N-phenethyl-N-benzyl-aminomethyl) - Nitrobenzene 4- (N-phenethyl-N-cyclohexyl-aminomethyl) -nicroLencene 4- [N- (2-Jpyridin-2-yl) -ethyl) -N-methyl-aminomethyl] -nitrobenzene 4- [N- ( 2- (pyridin-4-yl) -ethyl) -N-methyl-aminomethyl] -nitrobenzene 4- [N- (pyridin-4-yl-methyl) -N-methyl-aminomethyl] -nitrobenzene 4- (dibenzylamine-me tilt) -nitrobenzene 4- [N- (4-nitro-benzyl) -N-propyl-aminomethyl] -nitrobenzene 4- [N-benzyl-N- (3-cyano-propyl) -aminomethyl] -nitrobenzene 4- (N -benzyl-N-allyl-aminomethyl) -nitrobenzene 4- [N- (benzo (1,3) dioxol-5-yl-methyl) -N-methyl-aminomethyl] -nitrobenzene 4- (7-chloro-2, 3 , 4, 5-tetrahydro-benzo (d) azepin-3-yl-methyl) - itrobenzene 4- (7,8-dichloro-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl- methyl) -nitrobenzene 4- (7-methoxy-2,3,, 5-tetrahydro-benzo (d) azepin-3-ylmethyl) -nitrobenzene 4- (7-methyl-2,3,4,5-tetrahydro) -benzo (d) aze pin-3-yl-methyl) -nitrobenzene 4- (7,8-dimethoxy-2,3,4,5-tetrahydro-benzo (d) azepin-3-ylmethyl) -nitrobenzene 4- (6, 7-dichloro-l, 2, 3, 4-tetrahydro-isoquinolin-2-yl-methyl) -nitrobenzene 4- (6,7-dimethyl-l, 2,3,4-tetrahydro-isoquinolin-2-yl-methyl) ) -nitrobenzene 4- (6-chloro-1,2,3,4-tetrahydro-isoquinolin-2-ylmethyl) -nitrobenzene 4- (7-chloro-1,2,3,4-tetrahydro-isoquinoline-2) - il -me ti 1) -nitr-benzene 4- (6-methoxy-1,2,4,4-tetrahydro-isoquinolin-2-yl-methyl) -nitrobenzene 4- (7-methoxy-1, 2, 3, 4-tetrahydro-isoquinolin-2-yl-methyl) -nitrobenzene 4- (2,3,3,5-tetrahydro-azepino (4,5-b) pyrazin-3-yl-methyl) -nitrobenzene. 4- (7-amino-2, 3, 4, 5-tetrahydro-azepino (4,5-b) pyrazin-3-yl-methyl) -nitrobenzene 4- (2-amino-5,6,7, 8-tetrahydro-azepino (4,5-d) thiazol-6-yl-methyl) -nitrobenzene 4- (5,6,7,8-tetrahydro-azepino (4,5-d) thiazole or -li- methyl) -nitro-benzene EXAMPLE VI 4- (N-Ethyl-N-tert-butoxycarbonyl-amino ethyl) -nitrobenzene 2.2 g of 4 - (N-ethyl-1-aminome ti 1) -nitr or diene are dissolved in 50 ml of ethyl acetate and stirred for 30 minutes at room temperature with 2.6 g of di-tert-butyl dicarbonate. The solution is then washed with water and concentrated. Yield: 3.4 g (97% of theory), Rf value: 0.90 (silica gel, methylene chloride / methanol = 9: 1) Analogously to Example VI, the following compounds are prepared: 4- [N- ( 4-chlorophenylmethyl) -N-tert-but-oxycarboni 1-aminome thi 1)) - nor tr-benzene 4- (N-cyclohexyl-N-tert-butoxycarbonyl aminomethyl) -nitrobenzene 4- (N-isopropyl-N-tert-butoxycarbonyl) -aminomethyl) -nitrobenzene 4- (N-butyl-N-tert-butoxycarbonyl-aminomethyl) -nitrobenzene 4- (N-methoxycarbonylmethyl-N-tert-butoxycarbonyl-ami nome ti 1) -nitrobenzene 4- (N-benzyl) N-tert-butoxycarbonyl-aminomethyl) -nitrobenzene 4- (N-ethyl-N-tert-butoxycarbonyl-aminomethyl) -nitrobenzene Example VII 4- (N-Ethyl-N-tert-butoxycarbonyl-minomeyl) -aniline 6.4 g of 4 - (- eti 1 -N-tert -bu t ox ica rb oni 1 -aminome ti 1) - ni The benzene units are dissolved in 60 ml of methanol and hydrogenated at room temperature and 3 bars with 1.5 g of Raney nickel. Then, the catalyst is filtered off and the solution is concentrated. Yield: 4.78 g Rf value: 0.70 (silica gel, methylene chloride / methanol = 50: 1) Analogously to Example VII the following compounds are prepared: 4- [N- (4-chlorophenylmethyl) -N- tert-butoxycarbonyl-aminomethyl) -aniline 4- (N-cyclohexyl-N-tert-butoxycarbonyl-aminomethyl) -aniline 4- (N-isopropyl-N-tert-butoxycarbonyl-aminomethyl) -aniline 4- (N-butyl-N- tert-butoxycarbonyl-aminome ti 1) - ani 1 ina 4- (N-methoxycarbonylmethyl-N-tert-butoxycarbonyl-aminomethyl) -aniline 4- (N-benzyl-N-tert-butoxycarbonyl-aminomethyl) -aniline 4 - (pyrr ol idino -me t il) - ani 1 ina 4- (morpholino-methyl) -aniline 4- (piperidino-methyl) -aniline 4- (hexamethyleneimino-methyl) -aniline 4- (4-hydroxy-piperidino-methyl) - aniline 4- (4-methyl-piperidino-methyl) -aniline 4- (4-ethyl-piperidino-methyl) -aniline 4- (4-isopropyl-piperidino-methyl) -aniline 4- (4-phenyl-piperidino-methyl) ) -aniline 4- (4-benzyl-piperidino-methyl) -aniline 4- (4-ethoxycarbonyl-piperidino-methyl) -anyl to 4- (dimethylamino-met) il) -aniline 4- (di-n-propylamino-methyl) -aniline 4- (4-tert-butoxycarbonyl-piperazino-methyl aniline _ -3- (dimethylamino-methyl) -aniline 4- (2-diethylamino- e t il) -aniline. . 4 - (2-mo rfo 1 ino -eti 1) - ani 1 ina 4- (2-pyrrolidino-ethyl) -aniline 4- (2-piperidino-ethyl) -aniline 4- (N-ethyl-N-benzyl) aminomethyl) -aniline 4- (N-propyl-N-benzyl-aminomethyl) -aniline 4- (N-methyl-N- (4-chlorophenylmethyl) -ami nome ti 1) - an i 1 ina 4- (N-methyl) -N- (4-bromophenylmethyl) -aminomethyl) -aniline 4- (N-methyl-N- (3-chlorophenylmethyl) -aminomethyl) -aniline 4- (N-methyl-N- (3,4-dimethoxy-enylmethyl) - aminomethyl) -aniline 4- (N-methyl-N- (4-methoxyphenylmethyl) -aminomethyl) -aniline 4- [N- (2,2,2-trifluoroethyl) -N-benzyl-ami nome ti 1] - ani 1 i na N- (2,2,2-trifluoroethyl) -N- (4-chlorofenylmethyl) -aminomethyl] -aniline 4- 2, 6-dimethyl-piperidino-methyl) -aniline) 4 - . 4 - (ti orno rf lino-methyl) -aniline 4-S-oxide-thiomorpholino-methyl) -aniline 4- S, S-dioxido-thiomorpholino-methyl) -aniline 4-azetidino-methyl) -aniline 4- 2, 5-dihydropyrrol-l-yl-methyl) -aniline 4- 3,6-dihydro-2H-pyridin-1-yl-methyl) -anyl-4- (2-methoxycarbonyl-pyrrolidino-methyl) -ani 1 -na-4- 3 , 5-dimethyl-piperidino-methyl) -aniline 4- 4-phenyl-piperazino-methyl) -aniline 4- 4-phenyl-4-hydroxy-piperidino-methyl) -ani 1 ina-N- (3, 4, 5-trimethoxybenzyl) -N-methyl-amyne-butyl -aniline 4- N- (3,4-dimethoxybenzyl) -N-ethyl-aminomethyl-aniline 4- N-benzyl-N-ethyl-aminomethyl) -aniline 4- N - (3-Chlorobenzyl) -N-methyl-aminomethyl] -ani-1-N- (2,6-dichlorobenzyl) -N-methyl-amine -nene -aniline 4- [N- (4-trifluoromethyl-benzyl) -N- methyl aminomethyl] -aniline 4- N-benzyl-N-isopropyl-aminomethyl) -aniline 4- N-benzyl-N-tert-butyl-methyl-methyl) -ani-1 -na 4- (diisopropylamino-methyl) -aniline 4- (di-n-propylamino-methyl) -aniline 4- (diisobutylamino-methyl) -aniline 2, 3, 4, 5-tetrahydro-benzo (d) azepin-3-yl-methyl) -ynyl-4- 2, 3-dihydro-isaindol-2-yl-methyl) -aniline 4-6, 7- dimethoxy-1,2,4,4-tetrahydro-isoquinolin-2-ylmethyl) -aniline 1,2,4,4-tetrahydro-isoquinolin-2-ylmethyl) -aniline N- (2-hydroxyethyl) - N-benzyl-aminomethyl] -aniline '1-ethyl-pentyl) -N- (pyridin-2-ylmethyl) -aminomethyl] -aniline 4- N -phenethyl-N-methyl-aminomethyl) -aniline 4- N- (3, 4-dihydroxy-phenethyl) -N-methyl-ami nomethyl -aniline 4- N- (3, 4, 5-trimethoxy-phenethyl) -N-methyl-ami nyl-tyl-aniline 4- [N- (3,4-dimethoxy-phenethyl) -N-methyl) -aminomethyl-aniline 4- [N- (4-nitro-phenethyl) -N-methyl) -aminomethyl] -aniline 4- (N-phenethyl-N-benzyl) -aminomethyl) -aniline 4- (N-phenethyl-N-cyclohexyl-aminomethyl) -anyl to 4- [N- (2- (pyridin-2-yl) -ethyl) -N-methyl-aminomethyl] -aniline 4- [N- (2- (pyridin-4-yl) -eti l) -N-methyl-aminomethyl] -aniline 4- [N- (pyridin-4-yl-methyl) -N-methyl-aminomethyl] -aniline 4- (dibenzylamino-methyl) -aniline 4- [N- (4 -nitro-benzyl) -N-propyl-aminomethyl] -aniline 4- [N-benzyl-N- (3-cyano-propyl) -aminomethyl] • aniline 4- (N-benzyl-N-allyl-aminomethyl) -aniline 4- [N-benzyl-N- (2,2, 2-trif luorostil) -aminomethyl] -aniline 4- [N- (benzo (1,3) dioxol-5-ylmethyl) -N-methyl aminomethyl] -aniline 4- (7-chloro-2,3,4,5-tetrahydro-benzo (d) azepin-3-ylmethyl) -aniline 4- (7,8-dichloro-2,3,4,5) tetrahydro-benzo (d) azepin-3-yl-methyl) -aniline 4- (7-methoxy-2,3,4,5-tetrahydro-benzo (d) azepin-3-ylmethyl) -aniline 4- ( 7-methyl-2, 3, 4, 5-tetrahydro-benzo (d) azepin-3-yl-methyl) -aniline 4- (7,8-dimethoxy-2,3,4,5-tetrahydro-benzo (d) ) azepin-3-yl-methyl) -aniline 4- (6,7-dichloro-l, 2, 3, 4-tetrahydro-isoquinolin-2-yl-methyl) -aniline 4- (6,7-dimethyl-l) , 2, 3, 4-tetrahydro-isoquinolin-2-yl-methyl) -aniline 4- (6-chloro-l, 2,3,4-tetrahydro-isoquinolin-2-yl-methyl) ) -aniline 4- (7-chloro-l, 2,3,4-tetrahydro-isoquinolin-2-yl-methyl) -aniline 4- (6-methoxy-1,2,3,4-tetrahydro-isoquinoline-2) -yl-methyl) -aniline 4- (7-methoxy-1, 2, 3, 4-tetrahydro-isoquinolin-2-yl-methyl-1) - an i 1 i na 4- (2, 3, 4, 5-tetrahydro-azepino (4,5-b) pyrazin-3-yl-methyl) -aniline 4- (7-amino-2,3,4,5-tetrahydro-azepine (4,5-b) pyrazin-3) -yl-methyl) -aniline 4- (2-amino-5,6,7,8-tetrahydro-azepino (4,5-d) thiazol-6-ylmethyl) -aniline 4- (5,6,7) , 8-tetrahydro-azepino (4,5-d) thiazol-6-yl-methyl) -aniline Preparation of The final products: Example 1 3-Z- (1-f nylamino) -1-butylmethylene) -5-amido-2-indolinone 600 mg of a resin prepared according to Example IV are suspended in 3 ml of dimethylformamide -and shaken for 10 hours at 70 ° C with 0.4 g of aniline. It is then filtered off and the resin is washed several times with methylene chloride, methanol and dimethylformamide. Then, 3 ml of methanolic ammonia are added for 2 hours in order to separate the acetyl group. Finally, after a further washing with dimethylformamide and methylene chloride, 4 ml of 10% trifluoroacetic acid in methylene chloride are added over 90 minutes, the resin is separated and the solution is concentrated. The residue is taken up with a little 1N sodium hydroxide solution and extracted with a little methylene chloride. The organic phase is dried over sodium sulfate and concentrated by rotary evaporation. Yield: 37 mg, Rf value: 0.6 (silica gel, methylene chloride / methanol = 9: 1) C20H2? N3O2 mass spectrum: m / z = 335 (M +) Analogously to Example 1, the following are prepared compounds: (1) 3-Z- (1-f eni 1 ami no -me ti 1 en) -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (1) and aniline Rf Value: 0.59 (silica gel, methylene chloride / methanol = 9: 1) C? 6H13N302 mass spectrum: m / z = 279 (M +) (2) 3-Z- [1- (4-methyl-phenylamino) -1-methyl-methylene] -5-amido-2) -indolinone Prepared from the resin prepared according to Example IV (2) and 4 -me ti 1 ani 1 ina Rf Value: 0, 44 (silica gel, methylene chloride / methanol = 9: 1) C18H? 7N302 'mass spectrum: m / z = 307 (M +) (3) 3 - Z - [1 - (4-chloro-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone. Prepared from the resin prepared according to Example I (2) and 4-c 1 or oan i 1 na Rf value: 0.45 (silica gel, methylene chloride / methanol = 9: 1) C? 7H14ClN302 spectrum mass: m / z = 327/329 (M +) (4) 3-Z- [1- (4-ethyl-phenylamino) -l-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-ethi 1 ani 1 ina Value Rf_: 0.43 (silica gel, methylene chloride / methanol = 9: 1) C? 9H? 9N302 mass spectrum: m / z = 321 (M +) (5) 3-Z - [1 - (4-methoxy-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) ) and 4 -me toxi ani 1 ina Rf value: 0.46 (silica gel, methylene chloride / methanol = 9: 1) C? 8H? 7N303 mass spectrum: m / z = 323 (M +) (6) 3-Z- [l- (4-iodo-phenylamino) -l-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example I (2) and 4-y odoani 1 i na Rf Value: 0.36 (silica gel, chloride d methylene / methanol = 9: 1) C17H14N302 mass spectrum: m / z = 419 (M +) (7) 3 - Z - [1- (4-f luoro-phenylamino) -1-methyl-me ti 1 in] - 5 - ami do- 2 - i dolone Prepared from the resin prepared according to Example IV (2) and 4-f 1 uo r oani 1 i na Value Rf-: 0.60 (silica gel, chloride methylene / methanol = 9: 1) C? 7H? 4FN302 mass spectrum: m / z = 311 (M +) (8) 3-Z- [1- (4-bromo-phenylamino) -1-methyl-methylene] - 5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 -br omoani 1 ina Rf value: 0.53 (silica gel, methylene chloride / methanol = 9: 1 C? 7H? 4BrN302 mass spectrum: m / z = 371/373 (M +) (9) 3-Z- (1-phenylamino-l-methyl-methylene) - 5 -ami do -2-indo 1 inone Prepared from the resin prepared according to Example IV (2) and aniline Rf value: 0.58 (silica gel, methylene chloride / methanol = 9: 1) C? 7H? 5N302 mass spectrum: m / z = 293 (M +) (10) 3-Z- (1-amino-1-methyl-methylene) -5-amido-2-indolinone 'Pr prepared from the resin prepared according to Example IV (2) and ammonia. Rf value: 0.23 (silica gel, methylene chloride / methanol. = 9: 1) mass spectrum: m / z = 217 (M +) (11) 3-Z- [1- (4-piperidinomethyl-phenylamino) -1-methyl-methylene] -S-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (p ip eridi no -me ti 1) -aniline Rf value: 0.31 (silica gel, methylene chloride / methanol = 9: 1) C23 H2 gN 402 mass spectrum: m / z = 390 (M +) (12) 3-Z- [1- (4-pyrrolidinomethyl-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from of the resin prepared according to Example IV (2) and 4 - (1-pyrro-1-yl) -aniline Rf value 0.20 (silica gel, methylene chloride / methanol = 4: 1) CH 4N 4 -2 mass spectrum: m / z = 376 (M +) (13) 3-Z- [1- (4-dipropylaminomethyl-phenylamino) -1-methyl-methylene] -S-amido-2-indolinone Prepared from the resin prepared according to the Example 11 (2) and 4- (di-n-propylamino-methyl) -aniline Rf value: 0.71 (silica gel, methylene chloride / methanol = 4: 1) C24 H3 n 4? 2 mass spectrum: m / z = 406 (M +) (14) 3-Z- [l- [4- (2-piperidinoethyl) -phenylamino] -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (2-p ip eri di no-eti 1) -aniline Rf value: 0.38 (silica gel, methylene chloride / methanol = 4: 1) C24 H28N4 O 2 mass spectrum: m / z = 404 (M +) (15) 3-Z- [l- [4- (2-diethylaminoethyl) -phenylamino] -1-methyl-methylene] -5-amido-2-indolinone Prepared from prepared resin according to Example IV (2) and 4 - (2-di eti 1 ami nceti 1) -aniline Rf value: 0.33 (silica gel, methylene chloride / methanol = 4: 1) C23H28N402 mass spectrum: m / z = 393 (M +) (16) 3-Z- [1- (4-hexamethylene iminomethyl-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (hexame ti 1 enimino -methyl) -aniline Rf Value: 0, 34 (silica gel, methylene chloride / methanol = 4: 1) C24H28N O2 mass spectrum: m / z = 404 (M +) (17) 3-Z- [l- [4- (N-methyl-N -methanesulfonyl-amino) -phenylamino] -1-methyl-methylene] -5-amido-2-indo-1-inone. Prepared from the resin prepared according to Example IV (2) and 4 - (N-me ti 1 -N -methanesulfonyl-amino) -aniline Rf value: 0.36 (silica gel, methylene chloride / methanol = 9: 1) C? GH20N4O4S mass spectrum: m / z = 400 (M +) (18) 3-Z- [1- (4-methanesulfonylamino-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (me t ano s ul f oni 1 amino) -aniline Rf value: 0.31 (silica gel, methylene chloride / methanol = 9: 1) Ci8H? 8N404s: mass spectrum: m / z = 386 (M +) (19) 3-Z- [ l- (4-Bromophenylamino) -1-ethyl-methylene] -5-amido-2) -indolinone Prepared from the resin prepared according to Example IV (3) and 4 -br omoani 1 i na Rf Value: 0, 52 (silica gel methylene chloride / methanol = 9 : 1) C? 8H? 6BrN302 mass spectrum: m / z = 385/387 (M + / M + 2 +) (20) 3-Z- [1- (4-piperidinomethyl-phenylamino) -1-ethyl-methylene ] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (3) and 4- (p ip er idinome ti 1) - ani 1 i na Rf Value: 0.42 (silica gel, methylene chloride / methanol = 4: 1) C2 H28N402 mass spectrum: m / z = 404 (M +) (21) 3 - Z - [1 - (4-p ipe ri dino me ti 1 - f eni 1 ami no) - 1-propyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (4) and 4 - (p ipe ri di no -me ti 1) -aniline Rf Value: 0, 49 (silica gel, methylene chloride / methanol = 4: 1) C25H30N O2 mass spectrum: m / z = 418 (M +) (22) 3-Z- [1- (4-bromophenylamino) -l-propyl- me ti 1 en] - 5 - ami do - 2 - indole inona Prepared from the resin prepared according to Example IV (4) and 4 -br omoani 1 i na Rf Value: 0.53 (silica gel, chloride methylene / methanol = 9: 1) C? 9H? 8BrN302 mass spectrum: m / z = 309/401 (M + / M + 2 +) (23) 3-Z - [(4-bromophenylamino) -methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (1) and 4 -br omoani 1 i na C? 6H12BrN302 mass spectrum: m / z = 357/359 (M + / M + 2 +) (24) 3 -Z - [(4-piperidinomethyl-phenylamino) -methylene ] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (1) and 4 - (pipe r idino-me ti 1) -aniline mass spectrum: m / z = 376 (M +) ( 25) 3-Z- [1- (4-bromofenylamino) -1-butyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV and 4 -br omoa i 1 ina Value Rf: 0.53 (silica gel, methylene chloride / methanol = 9: 1) C2oH nBrN302 mass spectrum: m / z = 413/415 (M + / M + 2 +) (26) 3 - Z - [1 - (4-piperidinomethyl-phenylamino) -1-butyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV and 4 - (p ipe ri di no -me ti 1) -aniline Rf value: 0.48 (silica gel, methylene chloride / methanol = 4: 1) C2 eH32N 402 mass spectrum: m / z = 432 (M +) (27) 3 - Z - [1- (4-piperidinomethyl-phenylamino) -l-ethenyl-methylene] - 5-amido-2-indolinone Prepared from the prepared resin confer to Example IV (5) and 4 - (p ipe r idino -me ti 1) -aniline (28) 3-Z- [1- (4-piperidinomethyl phenylamino) -1- (3-bromopropyl) -methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (6) and 4 - (p ipe ri dino -me ti 1) - aniline (29) 3-Z- [1- (4-piperidinomethyl-phenylamino) -1- (2-phenylsulfonylethyl) -methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (7) ) and 4 - (p ipe ri dino -me ti 1 -) -aniline (30) 3-Z- [l- [4- (2,6-dimethylpiperidino-methyl) -phenylamino] -1-methyl-methylene] - 5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4- (2,6-dimethylpiperidinomethyl) -aniline (31) 3-Z- [1- (4-thiamorpholinomethyl-phenylamino) -l-methyl) -methylene] -5-ami do-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (t i or f or 1 ino -me t i 1) -aniline Rf Value: 0, 60 (silica gel, methylene chloride / methanol = 9: 1) C22H24N402S mass spectrum: m / z = 408 (M +) (32) 3-Z- [l - [(4-thiomorpholino-S-oxide- methyl) -phenylamino] -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (t-orno-1-ino-S- or xi) do-methyl) -aniline Rf value: 0.21 (silica gel, methylene chloride / methanol = 9: 1) C22H24N4? 3S mass spectrum: m / z = 425 (M + H +) (33) 3 - Z - [1 - [4 (thiomorpholino-S, S-dioxide-methyl) -phenylamino] -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (1-indo-S, S-dioxide-methyl) -aniline (34) 3 - Z - [1- (4-azetidinomethyl-phenylamino) -1-methyl-methylene] -5-amido-2- ester indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (azetidino -methyl) -aniline (35) 3-Z- [1- [4- (2,5-dihydropyrrol-1-yl) -methyl) -phenylamino] -1-methyl-methylene] -5-amido-2-indole Inona Prepared from the resin prepared according to Example IV (2) and 4 - (2, 5-dihydro-1-methyl-1-methyl) -aniline Rf value: 0.10 (silica gel, chloride methylene / methanol = 9: 1) C22H22N402 mass spectrum: m / z = 375 (M + H +) (36) 3-Z- [l- [4- (3,6-dihydro-2H-pyridine-l- il-methyl) -phenylamino] -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (2, 5 -dihi dr op irro 1 - 1-methyl-methyl) -aniline Rf value: 0.10 (silica gel, methylene chloride / methanol = 9: 1) C22H22N40 mass spectrum: m / z = 375 (M + H +) (36) 3-Z - [l- [4- (3,6-Dihydro-2H-pyridin-l-yl-methyl) -phenylamino] -1-methyl-methylene] -5-amido-2-indo-l-lone Prepared from the resin prepared according to Example IV (2) and 4 - (3,6-dihydric or -2 H -pyridin-1-yl-methyl) -aniline Rf value: 0.20 (silica gel, methylene chloride / methanol = 9: 1) C23H24N? 2 mass spectrum: m / z = 389 (M + H +) (37) 3-Z- [1- [4- (2-ethoxycarbon il-pyrrolidinomethyl-phenylamino] -1-methyl-methylene] -5-amido-2-n-1-one none Prepared from the resin prepared according to Example IV (2) and 4 - (2-ethoxycarbonyl) pyrrolidino-methyl) -aniline Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1) C24H26N4? 4 mass spectrum: m / z = 435 (M + H +) (38) 3-Z - [l- [4- (3,5-dimethyl-piperidino-methyl) -phenylamino] -l-methyl-methylen] -5-amido-2-indo-1 in on a Prepared from the prepared resin according to to Example IV (2) and 4 - (3, 5-dimethyl-1-piperidino-ethyl) -aniline R-value: 0.16 (silica gel, methylene chloride / methanol = 9: 1) C25 H30N402 mass spectrum : m / z = 418 (M +) (39) 3-Z - [1 - [4 - (4-phenyl-piperazino-methyl) -phenylamino] -1-methyl-me ti 1 in] - 5-ami trifluoroacetate do-2-indole inona Prepared from the resin prepared according to Example IV (2) and 4 - (4-f in i 1 -p ip erazi non-methyl) -aniline Rf value: 0.40 (silica gel , methylene chloride / methanol = 9: 1) C28H29N502 mass spectrum: m / z = 468 (M + H +) (40) 3-Z - [1 - [4 - (4-phenyl-4-hydroxy-piperidino-methyl) trifluoroacetate) phenylamino] -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (4-f eni 1-4 -hi dr oxy-p ipe ri di no -me ti 1) - ani 1 ina C29H3oN403 mass spectrum: m / z = 483 (M + H +) (41) 3 -Z - [1 - (3-methoxy-phenylamino) -1-methyl-methylene ] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 3-me t oxy-ani 1 i na Rf Value: O, 40 (silica gel, methylene chloride / methanol = 9: 1) C18H17N303 mass spectrum: m / z = 323 (M +) (42) 3-z- [1- (3-ethoxycarbonyl-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 3-amino-benzoic acid ethyl ester C2oH? 9N3? 4 mass spectrum: m / z = 365 (M +) (43) 3-Z- trifluoroacetate [l- (4-dimethylaminomethyl-phenyl amino) -1-methyl-methylene] - 5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-dimethyl ti 1 ami nome ti 1 -aniline C2oH22N 02 mass spectrum: m / z = 351 (M + H +) (44) 3-Z- [l- [4- (4-cyclohexyl-piperidino-methyl) -phenylamino] -1-methyl-methylene] -5-amido-2-indo-1 none Prepared from the resin prepared according to Example IV (2) and 4 - (4-ci c 1 ohe xi 1 -piperidino-methyl) -aniline (45) 3-Z- [1- (4-morpholino-phenylamino) -1-methyl-methylene ] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-mo rfo 1 ino-ani 1 i na C2? H22N403 mass spectrum: m / z = 378 (M +) (46) 3-z- [1- (N-methyl-piperidin-4-ylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV ( 2) and 4-ami not -N -me ti 1 -piperidine Ci7H 2N4? mass spectrum: m / z. = 314- (M +) l í (47) 3-z- [1- (4-methylcyclohexylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-methyl-1 - ci c 1 ohex i 1 ami na C? 8H23 3? 2 mass spectrum: m / z = 313 (M +) (48) 3-Z- (1-cyclopentylamino-l-methyl-methylene) -5-amido 2-indolinone Prepared from the resin prepared according to Example IV (2) and cich 1 op enti 1 amine Rf value: 0.70 (silica gel, methylene chloride / methanol = 4: 1) C16H19 3O2 mass spectrum : m / z = 285 (M +) (49) 3 - Z - (1 - is op r op i 1 ami no - 1 -me thi 1 -methylene) -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and isopropylamine C? 4H? 7N302 mass spectrum: m / z = 259 (M +) (50) 3-Z- [1- (4-ethoxycarbonylmethylaminomethyl-phenylamino) -1-methyl-methylene ] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (et ox i ca r boni Ime ti 1-N-tert-butyloxycarbonyl-amino-methyl) -aniline C21 H22N O4 mass spectrum: m / z = 394 (M +) (51) 3 - Z - [1 - (4 -benz i 1 ami nome ti 1 -phenylamino) -1-methyl-methylene] -5-amido-2 -indolinone Prepared from the resin prepared according to Example IV (2) and 4- (N-benzyl-N-tert-butyloxycarbonyl-aminomethyl) -aniline Rf value: 0.24 (silica gel, methylene chloride / methanol = 9: 1) C25H24N402 mass spectrum: m / z = 412 (M +) (52) 3-Z- [1- (4-Butylaminomethyl-phenylamino) -1-methyl-methylene] -5-amido-2-trifluoroacetate -indolinone Prepared from the resin prepared according to Example IV (2) and 4- (N-butyl-N-tert-butyloxycarbonyl-aminomethyl) -aniline Rf value: 0.40 (silica gel, methylene chloride / methanol = 4: 1) C22H26N402 mass spectrum: m / z = 378 (M +) (53) 3-Z- [l- (4-ethylaminomethyl-phenylamino) -l-methyl -methyl] -5-amido trifluoroacetate -2-indolinone Prepared from the resin prepared according to Example IV (2) and 4- (N-ethyl-N-tert-butyloxycarbonyl-aminomethyl) -aniline Rf Value: 0.20 (gel silica, methylene chloride / methanol = 4: 1) C2oH 2N40 mass spectrum: m / z = 351 (M + H +) (54) 3-Z- [1- (4-cyclohexylaminomethyl-phenylamino) trifluoroacetate -1- methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - [cyclohexyl] -1- (N-tert-butyloxycarbonyl-aminomethyl] -aniline C2 H 9N402 mass spectrum: m / z = 405 (M + H +) (55) 3-Z- [1- (4-isopropylaminomethyl-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone trifluoroacetate Prepared to starting from the resin prepared according to Example IV (2) and 4 - (N-isop op i 1-N-tert-butyloxycarbonyl-aminomethyl) -aniline C2? H24N402 1 mass spectrum: m / z = 365 (M + H +) (56) 3-Z- [1- (4-trifluoromethoxy-phenylamino) -l-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example I (2) and 4-trif 1 uo r ome t oxy -aniline C? 8H14F3N303 mass spectrum: m / z = 377 (M +) (57) 3-Z- [1- (4- difluoromethoxy-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-dif luoromethoxy-ani 1 ina Rf value: 0.5 (gel silica, methylene chloride / methanol = 9: 1) C18H? 5F2N303 mass spectrum: m / z = 359 (M + H +) (58) 3 - Z - [1- (4-bromo-3-chloro-phenylamino ) - 1 -methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-boron-3-c-1-one-i-na1 C17H13BrClN302 spectrum masses: m / z = 405/407/409 (M + / M + 2 + / M + 4 +) (59) 3-Z- [1- (4-trifluoromethyl-3-bromo-phenylamino) -1-methyl- methylene] -5-amido-2-indolinana Prepared from the resin prepared in accordance with Example IV (2) and 4-trif luoromethyl-3-romo-ani 1 ina C? 8H13BrF3N302 mass spectrum: m / z = 439/441 (M + / M + 2 +) (60) 3-Z- [1 - (4-chloro-phenylamino) -methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (1) and 4-c 1 gold -an i 1 ina CisHizCx ^ Oz mass spectrum : m / z = 312/314 (M +) (61) 3 - Z - [1 - (3-bromo-phenylamino) -1-methyl-me ti 1 in] - 5 - ami do - 2 - i nde 1 i none Prepared from prepared resin according to Example IV (2) and 3-bromo-aniline C? 7H? 4BrN302 mass spectrum: m / z = 371/373 (M +) (62) 3-Z- [1- (3-chloro-f-enylamino ) -1-methyl-me ti 1 in] - 5 - ami do - 2 - indole inone Prepared from the resin prepared according to Example IV (2) and 3 - c 1 gold - ani 1 i na C? 7H? 4C? N302 mass spectrum: m / z = 327/329 (M +) (63) 3-Z- [1- (2-chloro-phenylamino) -l-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 2-c 1 gold-ani 1 i na C? 7H? 4C? N302 mass spectrum: m / z = 327/329 (M +) (64) 3- Z- [1- (4-bromo-3-methyl-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-br - 3 -me ti 1 - an i 1 i na Rf Value: 0, 60 (silica gel, methylene chloride / methanol = 9: 1) C? 8H16BrN302 mass spectrum: m / z = 385/387 (M +) (65) 3 - Z - [1 - (4 -br omo - 3-methoxymethyl-1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-br omo-3-me t ox i - aniline Rf value: 0.60 (silica gel, methylene chloride / methanol = 9: 1) C? 8H? 6BrN303 mass spectrum: m / z = 401/403 (M +) (66) 3- Z- [1- (4-fluoro-3-nicro-phenylamino) -1-methyl-methylene] -5-amido-2-lindolinone Prepared from the resin prepared according to Example IV (2) and 4-f 1 uo ro - 3 -nitro -aniline Rf value: 0.40 (silica gel, methylene chloride / methanol = 9: 1) C17H13FN404 mass spectrum: m / z = 356 (M +) (67) 3 - Z - [ 1- (4-bromo-3-nitro-phenylamino) -1-methyl-methylene} -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-bromo-3-nitro-aniline Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1) Ci7H? 3BrN404 mass spectrum: m / z = 416/418 (M +) (68) 3-Z- [l- (4 ethyl-3-nitro-phenyl amino) -1-methyl-methylene) -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-ethi 1-3 ani 1 i na Rf value: 0.70 (silica gel, methylene chloride / methanol = 9: 1) C? 9H? 8N404 mass spectrum: m / z = 366 (M +) (69) 3 - Z - [ 1- (4-chloro-3-nitro-phenylamino) -1-methyl-methylene] -5-amido-2-indollnone Prepared from the resin prepared according to Example IV (2) and 4-c 1 gold-3 - nitro - an i 1 i na Ci7H13C? N404 mass spectrum: m / z = 371/373 (M +) (70) 3 - Z - [1 - (3-n-tro-f-en-lamino) -1-methyl-1-methylene] -5-amido -2-indolinone Prepared from the resin prepared according to Example IV (2) and 3-nitro-ani 1 i na mass spectrum: m / z = 338 (M + H +) (71) 3-Z- [1 - (4-Methyl-3-nitro-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-methyl-1-3 nitro-ani 1 i na Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1) C? 8H? 6N404 mass spectrum: m / z = 352 (M +) (72) 3-Z - [l- (4-Bromo-3-methoxycarbonyl-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and methyl ester of 2 -br omo-5-amino-ben z oi co Rf value: 0.50 (silica gel, methylene chloride / metansl = 9: 1) C? 9H? 6BrN304 mass spectrum: m / z = 429/431 ( M + H +) (73) 3-Z- [1- (4-carbamoyl-phenylamino) -1-methyl -methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 -aminobenzene ami da Rf value: 0.20 (silica gel, methylene chloride / methanol = 9 : 1) C? 9H16N403 mass spectrum: m / z = 336 (M +) (74) 3 - Z - [1 - (4 - (p ipe r idino-ca rboni 1) -phenylamino) -1-methyl-methylene ] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 1 - (4-ami no -b in zoi 1) -piperidine Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1) C23H24N403 mass spectrum: m / z = 404 (M +) (75) Trif luoroacetate of 3 - Z - [1 - (4 - (2 - (diethylamino) -ethyl-carbamoyl) - phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-amino - - [2 - (diethyl 1-amino) -ethe] -ben z ami da Rf value: 0.30 (silica gel, methylene chloride / methanol = 9: 1) C24 H29N5O3 mass spectrum: m / z = 436 (M + H +) (76) 3 -Z - [ 1- (4 -tri f lu oromet il-p-enylamino) -l-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-trif luoromethyl-ani 1 ina C? 8H? 4F3N302 spectrum mass: m / z = 361 (M +) (77) 3 - Z - [1 - (3-hydroxymethyl-phenylamino) -1-ethyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 3-aminobenzyl alcohol C? 8H? 7N303 mass spectrum: m / z = 323 (M +) (78) 3-Z- [1- (4- (hydroxycarbonyl-phenyl-amino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-amino-ene-enzoic acid RE Value: 0.20 (silica gel, chloride methylene / methanol = 4: 1) C18H15N304 mass spectrum: m / z = 336 (M-H +) (79) 3-Z- [1- (4-ethoxycarbonylmethyl-3-nitro-phenylamino) -1-methyl- methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-amino-2-nitro-phenylacetic acid ethyl ester Rf Value: O, 70 (g silica, methylene chloride / methanol = 9: 1) C21H20N4O6 mass spectrum: m / z = 424 (M +) (80) 3-Z- [l- (3-methoxycarbonyl-4-methyl-phenylamino) -1 -methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example 'IV (2) and methyl ester of 3-amino-6-methyl-1-benz oi co Value Rf: 0 , 70 (silica gel, methylene chloride / methanol = 9: 1) C2oH? 9N30 mass spectrum: m / z = 365 (M +) (81) 3-z- [1- (3-diet i 1 ca rb amo i 1-4 -methyl-phenyl-aminol-1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 3-amino acid diethylamide 6-methyl-benzoic Rf value: 0, 50 (silica gel, methylene chloride / methanol = 9: 1) C23H26N403 mass spectrum: m / z = 406 (M +) (82) 3-Z- [1- (3-ethylcarbamoyl-4-methyl-phenylamino ) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 3-amino-6-methyl-benzoic acid ethylamide Rf Value: 0.40 ( silica gel, methylene chloride / methanol = 9: 1) C2? H N40 mass spectrum: m / z = 378 (M +) (83) 3-Z- [1- (3-sulfamoyl-4-methyl-phenylamino ) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 3-amino-6-methyl-phenylsulphonic acid amide Rf value: 0.30 ( silica gel, methylene chloride / methanol = 9: 1) C18H18N4O4S mass spectrum: m / z = 386 (M +) (84) 3-Z- [1- (3-acetylamino-4-methyl-phenylamino) -1 -methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4-amino-2-a ce ti 1 ami no-toluene Rf Value: 0.65 ( silica gel, chloride methylene / methanol = 9: 1) C2oH2oN403 mass spectrum: m / z = 364 (M +) (85) 3-Z - [1 - (4 - (2-dimethylamino-ethoxy) -phenylamino) -1-methyl trifluoroacetate -methylene] -5-amido-2-indole-inone Prepared from the resin prepared according to Example IV (2) and 4 - (2-dimetho-1-ami-non-ethoxy) -aniline Rf value: 0.10 (gel silica, methylene chloride / methanol 4: 1) C21H24N403 mass spectrum: m / z = 380 (M +) (86) 3-Z - [1 - (4 - (2-piperidino-ethoxy) -phenylamino) trifluoroacetate) -1-methyl-methylene] - 5 -ami do-2-indole inone Prepared from the resin prepared according to Example IV (2) and 4 - (2-p ip eridino-ethoxy) -aniline Rf value: 0, 70 (silica gel, methylene chloride / methanol = 4: 1) C24H28N4? 3 mass spectrum: m / z = 420 (M +) (87) Trifluoroacetate 3-Z - [1 - (4 - (3-dimethylamino -propoxy) -phenylamino) -1-methyl-methylene] -5-amido-2-indole-inone Prepared from the resin prepared according to Example IV (2) and 4 - (3 -dime ti 1-amino -propoxy) -aniline Rf value: 0.10 (silica gel, methylene chloride / methanol = 4: 1) C22H2 eN 403 mass spectrum: m / z = 394 (M +) (88) 3-Z - [1 - (4 - (3-piperidino-propoxy) -phenylamino) -1-methyl-methylene] - 5 -amido-2-indo-1-indo tri? Uoroacetate Prepared from prepared resin according to Example IV (2) and 4- (3-piperidino-propoxy) -aniline Rf value: 0.20 (silica gel, methylene chloride / methanol = 4: 1) C25H30N4? 3 mass spectrum: m / z = 434 (M +) (89) 3-Z - [1 - (4 - (3 - (N-benzyl-N-methylamino) -propoxy) -phenylamino) -1-methyl-me ti-lene] - 5 - trifluoroacetate amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - [3 - (N-benzyl-N-methylamino) -propoxy] -aniline Rf value: .0.60 (gel silica, methylene chloride / methanol = 4: 1) C28 H30N 403 mass spectrum: m / z = 470 (M +) (90) 3 - Z - [1 - (4 - (N-benzyl-aminomethyl) - trifluoroacetate - phenylamino) -meti len] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (1) and 4- (N-benzyl-N-tert-butoxycarbonyl-aminomethyl) -aniline C24H22N4O2 mass spectrum: m / z = 399 (M + H +) (91) 3-Z - [1 - (4 - (N- (4-chlorobenzyl) -aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2- trifluoroacetate indolinone Prepared from the resin prepared according to Example IV (2) and 4 - [N- (4-c 1 or obenc i 1-N-tert-butoxycarbonyl-aminomethyl) -aniline Rf value: 0.40 (gel silica, methylene chloride / methanol = 9: 1) C25H23CIN4O2 mass spectrum: m / z = 446/448 (M +) (92) 3-Z - trifluoroacetate - [1 - (4 - (N- (3, 4, 5-trimethoxybenzyl) -N-methyl-aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinana Prepared from the resin prepared according to Example IV (2) and 4 - [N- ( 3, 4, 5-trimethoxy-benzyl) -N-methyl-aminomethyl] -aniline Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1) C29H32N405 spectrum e masses: m / z = 516 (M +) (93) 3-Z - trifluoroacetate - [1 - (4 - (N- (3), 4-dimethyloxybenzyl 1) -N-me ti 1 -benzyl) -N-methyl-aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indo-1-inone Prepared from the resin prepared according to Example IV (2) and 4 - [N - (3,4-dimethoxy-benzyl) -N-methyl-aminomethyl] -aniline Rf value: 0.40 (silica gel , methylene chloride / methanol = 9: 1) C28H3o 4? 4 mass spectrum: m / z = 486 (M +) (94) 3-Z - trifluoroacetate - [1 - (4 - (N- (3, 4 - dimethoxy-benzyl) -N-ethyl-aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - [N- ( 3, -dime t-oxy-benzyl) -N-ethyl-aminomethyl] -aniline Rf value: 0.40 (silica gel, methylene chloride / methanol = 9: 1) C29H32N404 mass spectrum: m / z = 500 ( M +) (95) Trifluoroacetate 3-Z - [1 - (4 - (N-benzyl-N-ethyl-aminomethyl) -phenylamino) -1-methyl-me ti 1 in] - 5 - ami do - 2 - i No 1 none Prepared from the resin prepared according to Example IV (2) and 4 - (N-benzyl 1 -Ne ti 1 -aminomethyl) -aniline Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1) C27H29N402 mass spectrum: m / z = 440 (M + ) (96) 3 - Z - [1 - (4 - (N-benzyl-N-methyl-aminomethyl) -phenylamino) -1-methyl-me ti 1 in] - 5 - ami do -2 - i ndol trifluoroacetate Inona Prepared from the resin prepared according to Example IV (2) and 4 - (-benzyl-1-N-meth i 1 -aminomethyl) -aniline Rf value: 0.55 (silica gel, methylene chloride / methanol = 9: 1) C26H26N402 mass spectrum: m / z = 426 (M +) (97) 3-Z - [1 - (4 - (N-benzyl-N-methyl-aminomethyl) -phenylamino) -1-ethyl trifluoroacetate -me ti 1 en] - 5 - amido -2 - indo 1 inona Prepared from the resin prepared according to Example IV (3) and 4 - (N-benz i 1 -N -me thi 1-aminomethyl) -aniline Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1) C27H28N402 mass spectrum: m / z = 440 (M +) (98) 3 - Z - trifluoroacetate - [1 - (4 - ( -benzyl-N-methyl-aminomethyl l) -phenylamino) -1-propyl-me ti len] -5-ami do -2-indo 1 inone Prepared from the resin prepared according to Example IV (4) and 4 - (N-benzyl 1 -N- met i 1 -amino-methyl) -aniline Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1) C28H3oN402 mass spectrum: m / z = 454 (M +) (99) Trifluoroacetate of 3 -Z - [1 - (4 - (N- (4-chlorobenzyl) -N-methyl-aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone.

Prepared from the resin prepared according to Example IV (2) and 4 - [N - (4-c 1 or obenci 1) -N-me ti 1-aminome ti 1] - ani 1 i na Rf Value: 0, 40 (silica gel, methylene chloride / methanol = 9: 1) C26H25C? N4? 2 mass spectrum: m / z = 460/462 (M +) (100) Trifluoroacetate of 3-Z - [1 - (4 - (N - (3-chlorobenzyl) -N-methyl-aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - [N - (3-c 1 or obenc i 1) -N-methyl-aminomethyl] -aniline Rf value: 0.40 (silica gel, methylene chloride / methanol = 9: 1) C26H25CIN4O2 mass spectrum: m / z = 460/462 (M +) (101) 3-Z - [1 - (4 - (N - (2,6-dichlorobenzyl) -N-methyl-aminomethyl) -phenylamino) -1-methyl-methylene] trifluoroacetate] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4- [N- (2,6-dichlorobenzyl) -N-methyl-aminomethyl] -aniline Rf Value: 0.38 (silica gel, methylene chloride no / methanol = 9: 1) C26H24C? 2 402 mass spectrum: m / z = 494/496/498 (M + 2 + / M + 4 +) (102) 3-Z - Trifluoroacetate - [1 - (4 - (N - (4-trifluoromethylbenzyl) -N-methyl-aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - [N- (4-trifluoromethylbenzyl) -N-methyl-aminomethyl] -aniline Rf value: 0.38 (silica gel, methylene chloride / methanol = 9: 1) C27H25F3N402 mass spectrum: m / z = 494 ( M +) (103) 3-Z - [1 - (4 - (-benzyl-N-isopropyl-aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone trifluoroacetate Prepared from resin prepared according to Example IV (2) and 4 - (N -benzyl-1-N-isopropyl-aminomethyl) -aniline Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1) C28H30N402 spectrum mass: m / z = 454 (M +) (104) 3-Z - [1 - (4 - (N-benzyl-N-tert-butyl-aminomethyl) -phenylamino) -1-methyl-methylene] trifluoroacetate] - 5-amido-2-indolinone P repaired from the resin prepared according to Example IV (2) and 4- (N-benzyl-N-tert-butyl-aminomethyl) -aniline Rf value: 0.50 (silica gel, methylene chloride / methanol = 9 : 1) C29H32N402 mass spectrum: m / z = 468 (M +) (105) 3-Z - [1 - (4 - (N-benzyl-N-methyl-aminomethyl) -phenylamino) -methylene] - 5-trifluoroacetate] -amido-2 -indole Inona Prepared from the resin prepared according to Example I (1) and 4 - (N-benzyl-1-N-me ti-1-aminomethyl) -aniline C25 H24N402 mass spectrum: m / z = 413 (M + H +) (106) 3-Z - [1 - (4 - (N-benzyl-N-ethyl-aminomeyl) -phenylamino) -1-methyl-methylene] -5-amido- trifluoroacetate 2-indolinone Prepared from the resin prepared according to Example IV (1) and 4 - (N-benzyl 1 -Ne ti 1 -aminomethyl) -aniline C26H26N402 mass spectrum: m / z = 427 (M + H +) ( 107) 3-Z- [l- (4- (diisopropylamino-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone trifluoroacetate Prepared from the resin prepared according to to Example IV (2) and 4 - (diis op r op i 1 ami non-methyl) -aniline Rf value: 0.50 (silica gel, methylene chloride / methanol = 4: 1) C24H3oN4? 2 mass spectrum : m / z = 406 (M +) (108) 3-Z - [1 - (4 - (di-n-propylamino-methyl) -phenylamino) -methylene] -5-amido-2-indo 1-indo trifluoroacetate Prepared from the resin prepared according to Example IV (2) and 4 - (di-n-pr or i1-amino-methyl) -aniline C23H28N402 mass spectrum: m / z = 393 (M + H +) (109) Trifluoroacetate of 3-Z - [1 - (4 - (diisobutylamino-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (di is obu ti 1 amino-me ti 1) - ani 1 ina Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1) C26H34N4? 2 mass spectrum: m / z = 434 (M +) (110) 3-Z- [l- (4- (2, 3, 4, 5-tetrahydro-benzo (d) azepin-3-yl-methyl) -phenylamino) -1-methyl-methylene trifluoroacetate ] -5-amido-2-indolinone Prepared from of the resin prepared according to Example IV (2) and 4 - (2), 3, 4, 5 - tetr ahi dr o -benzo (d) azepin-3-yl-methyl) -aniline Rf value: 0.30 (silica gel, methylene chloride / methanol = 9: 1) C28H28N402 spectrum masses: m / z = 452 (M +) (111) '3-Z- [l- (4- (l, 3-dihydro-isoindol-2-yl-methyl) -phenylamino) -1-methyl-methylene trifluoroacetate ] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (1,3-dihydro or -isoi ndol-2-i 1 -me ti 1) - ani 1 ina Rf value: 0.35 (silica gel, methylene chloride / methanol = 9: 1) C26H24N402 mass spectrum: m / z = 425 (M + H +) (112) 3 - Z - trifluoroacetate - [1 - ( 4- (6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinolin-2-ylmethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indo 1 inone Prepared from of the resin prepared according to Example IV (2) and 4- (6,7-d-imethoxy-1, 2, 3, 4-tetrahydro-isoquinolin-2-yl-methyl) -aniline Rf value: 0.50 ( silica gel, methylene chloride / methanol = 9: 1) C2gH30N4? 4 mass spectrum: m / z = 4 99 (M + H +) (113) 3-Z- [1- (4- (1, 2, 3, 4-tetrahydro-isoquinolin-2-yl-methyl) -phenylamino) -1-methyl-methylene] trifluoroacetate] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4- (1, 2, 3, 4-tetrahydro-isoquinolin-2-yl-methyl) -aniline (114) Trifluoroacetate of 3-Z - [1 - (4 - (N- (ethoxycarbonylmethyl) -N-benzyl-aminomethyl) -phenyl-amino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4- [N- (ethoxycarbonylmethyl) -N-benzyl-aminomethyl) -aniline Rf value: 0.60 (silica gel, methylene chloride / methanol = 9: 1) C2gH oN4? 4 mass spectrum: m / z = 498 (M +) (115) 3-Z - [1 - (4 - (N - (2-hydroxyethyl) -N-benzyl-aminomethyl) -phenylamino) -1-methyl trifluoroacetate -methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - [- (2-hi-dr-oxy-1-yl) -benzyl-aminomethyl) -aniline Rf Value: 0.40 (silica gel, chlorur or methylene / methanol 9: 1) C27H28N4? 3 mass spectrum: m / z = 456 (M +) (116) 3-Z - [1 - (4 - (N - (1-ethyl-pentyl) trifluoroacetate - N- (pyridin-2-yl-methyl) -aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - [ N - (1-eti 1 -p in ti 1) -N- (pyridin-2-yl-methyl) -aminomethyl] -aniline Rf value: 0.45 (silica gel, methylene chloride / methanol = 9: 1 ) C3? H37N502 mass spectrum: m / z = 511 (M +) (117) 3-Z- [1- (4- (piperidino-methyl) -3-nitro-phenylamino) -1-methyl-methylene] -5 amido-2-indolinone Prepared from the resin prepared according to Example IV (2) and 4 - (p ipe r idi o -me ti 1) -3-nitro-aniline Rf value: 0.70 (silica gel , methylene chloride / methanol = 9: 1) C23H25N5O4 mass spectrum: m / z = 436 (Mf-H +) (118) 3-Z - [1 - (4 - (N-phenethyl-N-methyl- trifluoroacetate aminomethyl) -phenylamino) -1-methyl-me ti 1 in] - 5 - ami do - 2 - indole indole Pr Prepared from the resin prepared according to Example IV (2) and 4 - (N-f ene ti 1-N-me ti 1-aminomethyl) -aniline Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1) C27H28N 02 mass spectrum: m / z = 441 (M + H +) (119) 3-Z- [1- (4- (N-phenethyl-N-ethyl-aminomethyl) -phenylamino) - 1-Methyl-methylene] -5-amido-2-indolone (120) 3-Z- [1- (4- (N- (3,4-dihydroxy-phenethyl) -N-methyl-aminomethyl) - phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (121) 3-Z- [1- (4- (N- (3,4,5-trimethoxy-phenethyl) -N-methyl-aminomethyl) ) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (122) 3-Z- [l- (4- (N- (3,4-dimethoxy-phenethyl) -N-methyl-aminomethyl) ) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (123) 3-Z- [l- (4- (N- (4-n-tro-lene-tyl) -N-met-il- aminome ti 1) -fe nil mine) - 1-methyl-methylene] - 5 -amido-2-indolinana (124) 3-Z- [1- (4- (N-eethyl-N-benzyl-aminomethyl) -phenylamino) 1-methyl-methylene] -5-amido-2-indo-1-inone (125) 3-Z- [1- (4- (N-phenethyl-N-cyclohexyl-aminomethyl) -phen lamino) -1-methyl-methylene] -5-amido-2-indolinone (126) 3-Z- [l- (4- (N- (4-nitro-phenethyl) -N-isopropyl-aminomethyl) -phenylamino) -1 -methyl-methylene] -5-amido-2-indolinone (127) 3-Z- [1- (4- (N- (2- (pyridin-2-yl) -ethyl) -N-methyl-aminomethyl) - phenylamino) -1-methyl-methylene] -5 -amido-2-lindolinone (128) 3-Z- [1- (4- (N- (2- (pyridin-4-yl) -ethyl) -N-methyl -aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (129) 3-Z- [l- (4- (N- (pyridin-2-yl-methyl) -N-methyl) -aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (130) 3-Z- [l- (4- (N- (pyridin-3-yl-methyl) -N-me til -aminomethyl) -phenylamino) -l-methyl-methylen] -5-amido-2-indolinone (131) 3-Z- [l- (4- (N- (pyridin-4-yl-methyl) -N -methyl-aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (132) 3-Z- [1- (4- (dibenzylamino-methyl) -phenylamino) -1-methyl-methylene ] -5-amido-2-indolinone (133) 3-Z- [l- (4- (N- (4-nitro-benzyl) -N-propyl-aminomethyl) -phenylamino) -1-methyl-methylene] - 5 -amido-2-indolinone (134) 3-Z- [1- (4- (N-benz il-N- (3-cyano-propyl) -aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (135) 3-Z- [l- (4- (N-benzyl- N-allyl-aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (136) 3-Z- [l- (4- (imidazol-l-yl-methyl) -phenylamino) - 1-methyl-methylene] -5-amido-2-indolinone (137) 3-Z- [1- (4- (imidazol-2-yl-amino-methyl) -phenylamino) -1-methyl-methylene] -5 -amido-2-indolinone (138) 3-Z- [l- (4- (N-benzyl-N- (2, 2,2-trifluoroethyl) -aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (139) 3-Z- [l- (4- (N- (benzo (l, 3) dioxol-5-ylmethyl) -N-methyl-aminomethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (140) 3-Z- [1- (4- (7-chloro- 2, 3, 4, 5 tetrahydro-benzo (d) azepin-3-yl-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (141) 3-Z- [1- ( 4- (7,8-dichloro-2,3,4,5-tetrahydro-benzo (d) aze? In-3-yl-methyl) -phenylamino) -l-methyl-methylene] -5-amido-2-indolinone (142) 3-Z- [l- (4- (7-bromo-2,3,4,5-tetrahydro-benzo (d) -azepin-3-yl-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (143) 3-Z- [1- (4- (7-fluoro-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl-methyl) -phenylamino) - 'l-methyl-methylene] -5-amido-2-indolinone (144) 3-Z- [l- (4- (7-methoxy-2,3,4,5-tetrahydro-benzo (d) azepin-3 -yl-methyl) -phenylamino) -1-methyl-rt-ethylene] -5-amido-2-indolinone (145) 3-Z- [1- (4- (7-methyl-2, 3, 4, 5 tetrahydro-benzo (d) azepin-3-yl-methyl) -phenylamino) -1-methyl-methylene] -5- amido-2-indolinone (146) 3-Z- [l- (4- (7,8-dimethoxy-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl-methyl) -phenylamino) - l-methyl-methylene] -5-amido-2-indolinone (147) 3-Z- [1- (4- (6,7-dichloro-l, 2,3,4-tetrahydro-isoquinoline-2-l il-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (148) 3-Z- [1- (4- (6,7-dimethyl-1, 2,3,4- tetrahydro-isoquinolin-2-yl-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinana (149) 3-Z- [1- (4- (6,7-dif luoro-1 , 2, 3, 4-tetrahydro-isoquinolin-2-yl-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (150) 3-Z- [1- (4- (6 -chloro-l, 2,3,4-tetrahydro-isoquinolin-2-yl-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (151) 3-Z- [l- ( 4- (7-chloro-l, 2,3,4-tetrahydro-isoquinolin-2-yl-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (152) 3-Z- [1- (4- (6-methoxy-l, 2,3,4-tetrahydro-isoquinolin-2-yl-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (153) .. 3-Z- [1- (4- (7-methoxy-1, 2, 3, 4-tetrahydro-isoquinolin-2-yl) -methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (154) 3-Z- [1- (4- (2,3,4,5-tetrahydro-azepine (4 , 5-b) pyrazin-3-yl-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (155) 3-Z- [1- (4- (7-amino-2 3,4,5-tetrahydro-azepino (4,5-b) pyrazin-3-ylmethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone (156) 3-Z- [1- (4- (2-amino-5,6,7,8-tetrahydro-azepino (4,5-d) -thiazol-6-ylmethyl) -phenylamino) -1-methyl-methylene] -5 -amido-2-in-dolinone (157) 3-Z- [1- (4 - (5,6,7,8-tetrahydro-azepino- (4,5-d) thiazol-6-yl-methyl) - phenylamino) -1-methyl-methylene) -5-amido-2-indolinana (158) 3-Z - [1 - (pyridin-3-yl-amino) -l-methyl-methylene] -5-amido-2-indolinone (159) 3-Z- [1- (thiazol-2-yl-amino) -l-methyl-methylene] -5-amido-2-indolinone (160) 3-Z - [1 - (benzimidazol-2-yl -amino) -1-methyl-methylene] -5-amido-2-indolinone (161) 3-Z- [1- (5-methyl-isoxazol-3-yl-amino) -1-methyl-methylene] -5 -amido-2-indolinone (162) 3-Z- [1- (imidazol-2-yl-amino) -l-methyl-methylene] -5- amido-2-indolinone (163) 3-Z- [1- (5-methyl-pyridin-2-yl-amino) -1-methyl-methylene] -5-amido-2-indolinone (164) 3-Z- [1- (5-bromo-pyridin-2-yl-amino) l-methyl-methylene] -5-amido-2-indolinone (165) 3-Z- [1- (2-chloro-pyridin-5-yl -Not me) 1-methyl-methylene] -5-amido-2-indolinone Example 2 3-Z- [1- (4-Diethylcarbamoyl-phenylamino) -1-methyl-methylene] -5-amido-2-indolinana 2 g of resin, from the resin prepared according to Example 5 IVb, are reacted , analogously to Example 1, with 2 g of 4-aminobenzoic acid ethyl ester in dimethylformamide at 110 ° C. The wet loaded resin is suspended in 15 ml of dioxane and 15 ml of methanol and stirred for 40 hours with 12 ml of IN sodium hydroxide solution. It is then neutralized with dilute hydrochloric acid and washed with methylene chloride, methanol and dimethylformamide. Then 300 mg of the resin is suspended in 3 ml of dimethylformamide and left to stand for 40 hours at room temperature with 0.2 ml of diethylamine, 0.5 g of TBTU (O-benzotriazole tetrafluoroborate-1). il-N, N, N ', N'-tetramethyluronium) and 0.8 ml of N-ethyl-1-di is op r op i 1 amine. Finally, the product is separated from the resin as described in Example 1. Yield: 61 mg, Rf value: 0.30 (silica gel, methylene chloride / methanol = 9: 1) C22H24N403 spectrum masses: m / z = 392 (M +) Analogously to Example 2 the following compounds are prepared: (1) 3-Z - [1 - (4-benzyl ca ca bama i 1 -f eni 1 ami no) - 1- phenyl-methylene] -5-amido-2-indolinone Prepared analogously to Example 2 with benzyl amine. Rf value: 0.30 (silica gel, methylene chloride / methanol = 9: 1) C25H22N4? 3 mass spectrum: m / z = 426 (M +) (2) 3-Z- [l- (4- ( N-methoxycarbonylmethylcarbamoyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared analogously to Example 2 with ester g 1 ic ine ti 1 i co. Rf value: 0.50 (silica gel, methylene chloride / methanol = 9: 1) C2? H2ON405 mass spectrum: m / z = 408 (M +) (3) 3-Z- [1- (4-dimethylcarbamoyl phenylamino) -1-phenyl-methylene] -5-amido-2-indoleone Prepared analogously to Example 2 with dimethylamine. Rf value: 0.40 (silica gel, methylene chloride / methanol = 9: 1); C2? H2? N403 mass spectrum: m / z = 364 (M +) _ (4) Trif luoroacet ato_ of 3 - Z - [L_- (4 - (N - (2-piperidino-ethyl) -ca rbamoyl) - phenylamino) -1-methyl-methylene] -5-am? do-2-indolinone Prepared analogously to Example 2 with 1- (2-amino-ethyl) -piperidine Rf value: 0.30 (silica gel, methylene chloride / methanol = 4: 1) C25H25N503 mass spectrum: m / z = 448 (M + H +) (5) 3-Z - [1 - (4 - (-methyl-1-piperazinecarbamoyl) -phenylamino) trifluoroacetate) -1-phenyl-methylene] -5-amido-2-indolinone Prepared analogously to Example 2 with N-methyl-piperazine. Rf value: 0.40 (silica gel, methylene chloride / methanol = 4: 1) C23H25N503 mass spectrum: m / z = 419 (M +) (6) 3 - Z - trifluoroacetate - [1 - (4 - ( N - (2-diethylamino-ethyl) -N-methyl-carbamoyl) -phenylamino) -1-phenyl-methylene] -5-amido-2-indolinone Prepared analogously to Example 2 with N, N-diethyl-N'-methyl -ethylenediamine. Rf value: 0.20 (silica gel, methylene chloride / methanol = 4: 1) C25H31N503 mass spectrum: m / z = 449 (M +) (7) 3-Z- [1- (4-butylcarbamoyl-phenylamino ) - 1-phenyl-methylene] -5-amido-2-indolinone Prepared analogously to Example 2 with butylamine. Rf value: 0.80 (silica gel, methylene chloride / methanol = 4: 1) C22H2 N O3 mass spectrum: m / z = 392 (M +) Example 3 3-z- [1- (4- (N-methyl-N-benzoyl-amino) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone 4.5 g of a The resin prepared according to Example IVb is reacted, analogously to Example 1, with 3.4 g of 4- (9H-f-lor-9-i 1 -me toxy-carboni-1) -methyl-1-amino) -ani 1 na in dimethylformamide. Then, the group 9 H-f 1 uo r en-9 -i 1 -methyl oxacabonboni is separated with 40 ml of 30% pyridine in dimethylformamide, and the resin is washed several times. Next, 400 mg of the resin is suspended in 4 ml of dimethylformamide and 0.3 ml of triethylamine and reacted for one hour at room temperature with 0.3 ml of benzoyl chloride. Finally, the product is separated from the resin with trifluoroacetic acid as described in Example 1. Yield: 25 mg, • Rf value: 0.51 (silica gel, methylene chloride / methanol = 9: 1) C30H24N4? 3 mass spectrum: m / z = 426 (M +) Analogously to Example 3 the following compounds are prepared: (1) ) 3-Z- [1- (4 - (N-met i 1 -N-pr op ioni 1 -amino) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared analogously to Example 3 with propionic acid chloride. Rf value: 0.52 (silica gel, methylene chloride / methanol = 9: 1) C? H22N40 mass spectrum: m / z = 378 (M +) (2) 3-Z- [l- (4- ( N-methyl-N-butyryl-amino) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared analogously to Example 3 with butyric acid chloride. Rf value: 0.28 (silica gel, methylene chloride / methanol = 9: 1) C22H24N403 mass spectrum: m / z = 392 (M +) (3) 3-Z- [l- (4- (N- methyl-N-ethanesulfonyl-amino) -phenylamino) -methyl-methylene] -5-amido-2-indolinone Prepared analogously to Example 3 with its acid chloride and its ionic acid. Rf value: 0.30 (silica gel, methylene chloride / methanol = 9: 1) C2oH22N404S mass spectrum: m / z = 413 (M-H +) (4) 3-Z- [1- (4 - ( N-methyl-N-propanesulfonylamino) -phenylamino) -1-methyl-methylene] -5-amido-2-indo-1-inone Prepared analogously to Example 3 with pr opoxide acid chloride.

Rf value: 0.31 (silica gel, methylene chloride / methanol = 9: 1) C2lH24N4? 4S mass spectrum: m / z = 451 (M + Na +) (5) 3-Z- [1- (4 - (N-Methyl-N-phenylsulfonylamino) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared analogously to Example 3 with phenyl-1-chloro-1-oneic acid chloride. Rf value: 0.46 (silica gel, methylene chloride / methanol = 9: 1) C24H22N4O4S mass spectrum: m / z = 462 (M +) (6) 3-Z- [l- (4- (N- methyl-N-acetylamino) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared analogously to Example 3 with acetyl chloride. Rf value: 0.20 (silica gel, methylene chloride / methanol = 9: 1) C20H20N4? 3 mass spectrum: m / z = 364 (M +) (7) 3-Z- [1- (4- ( N-methyl-N-phenylmethylsulfonyl-amino) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared analogously to Example 3 with f-hydrophilic acid chloride. Rf value: 0.43 (silica gel, methylene chloride / methanol = 9: 1) C25H24N404S mass spectrum: m / z = 475 (M-H +) EXAMPLE 4 3-Z - [1- (4 - (N-Benzyl-N-methyl-butyl-methyl) -phenylamino) -1-methyl-methylene] -5-amido-2-indolinone- methyl ester 5-carboxylic acid 8.0 g (28 mmol) of l-acetyl-3- (1-ethoxy-l-methyl-methylene) -2-indolinone-5-ca-carboxylic acid methyl ester are dissolved in 60 ml of dimethylformamide and shaken with 6.3 g (28 mmol) of 4 - (N-benzyl-N-methyl-1-aminome-ti-1-an-i-na) for 6 hours at 80 ° C. Then, 30 ml of concentrated ammonia is added and it is allowed to stand for 2 hours at 45 ° C. The solution is concentrated by evaporation and the residue is washed with ethanol and ether. It is then chromatographed through a small column of silica gel with ethyl ester of acetic acid / ethane 1 (9: 1). Yield: 8.6 g (70% of theory), melting point: 150-152 ° C C27H27 303 mass spectrum: m / z = 442 (M +) Analogously to Example 4 the following compounds are prepared: (1) Ester 3-Z- [l- (4- (piperidino-methyl) -phenylamino) -1-methyl-methylene] -2-indolinone-5-carboxylic acid methyl C24H27N303 mass spectrum: m / z = 406 (M + H +) (2) 3-Z- [1- (4-bromo-phenylamino) -1-methyl-methylene] -2-indolinone-5-ca-carboxylic acid methyl ester C? 8H? 5BrN203 mass spectrum: m / z = 386/388 (M +) (3) 3-Z- [1- (4-Chloro-phenylamino) -1-methyl-methylene] -2-indolinone-5-carboxylic acid methyl ester C18H15C1N203 masses: m / z = 342/344 (M +) (4) 3-Z - [1 - (4 - (-methyl-N-methylsulfonyl-amino) -phenylamino) -1-ethyl-methylene] - methyl ester - 2-indolinone-5-carboxylic C2oH2? N305S mass spectrum: m / z = 415 (M +) (5) 3-Z- [l - (4 (2, 3, 4, 5-tetrahydro-benzo) methyl ester (d) azepin-3-yl-methyl) -phenylamino) -1-methyl-methylene] - 2-indolinone-5-carboxylic C29H 9N 02 mass spectrum: m / z = 467 (M +) E n g lis 5 Acid 3-Z- [1- (4- (N-benzyl-N-methyl-aminomethyl) -phenylamino) -1-methyl-methylene-1-2-indollnana-5-carboxylic acid 2.3 g (5 mmol) of 3-Z - [1- (4- (N-benzyl-N-methyl-aminomethyl) -phenylamino) -1-methyl-methylene] -2-indolinone-5-carboxylic acid methyl ester are dissolved in 50 ml of methanol and 50 ml of dioxane and stirred with 25 ml of IN sodium hydroxide solution for 1 hour at 70 ° C. It is then neutralized with 25 ml of IN hydrochloric acid and concentrated to dryness. The residue is washed several times with water and dried. Yield: 1.9 g (85% of theory), C2SH25N303 mass spectrum: m / z = 428 (M + H +) Analogously to Example 5 the following compounds are prepared: (1) Acid 3 -Z - [1 - ( 4 - (piper idino-me ti 1) -phenylamino) -1-methyl-methylene] -2-indolinone-5-carboxylic acid C23H2sN30 mass spectrum: m / z = 392 (M + H +) (2) 3-Z acid - [1 - (4-bromo-phenyl-1-amino) -1-methyl-methylene] -2-indolinone-5-carboxylic acid (3) 3-Z - [1 - (4-c 1 -o -f in i 1 amino) -1-methyl-methylene] -2-in-dolinone-5-carboxylic acid C? 7H? 3 ClN203 mass spectrum: m / z = 327/329 (M-H +) (4) 3-Z- [1-Acid] - (4 - (N-Methyl-N-methylsulfonyl-amino) -phenylamino) -1-methyl-methylene] -2-indolinone-5-carboxylic C19H19N305S mass spectrum: m / z = 401 (M +) (5) Acid 3-Z- [1- (4 - (2, 3, 4, 5-tet) rahydro-benzo (d) azepin-3-yl-methyl) -phenylamino) -1-methyl-methylene] -2-indolinone-5 -carboxylic C28H27N303 mass spectrum: m / z = 453 (M +) Example 6 3-Z- [l- (4- (N-benzyl-N-methyl-aminomethyl) -phenylamino) -1-methyl-methylene] -2-indolinone-5-diethylcarbamoyl-2-indolinone 0 , 3 g of 3-z - [1 - (4 - (N-benzyl-1-N-methyl-1-aminomethyl) -phenylamino) -1-methyl-methylene] -2-n-1-inone-2-indole inona-5-caboxy 1 i co are dissolved with 1.2 g of N-ethyl-1-di-op-i-1 and 1-amine in 8 ml of dimethylformamide. Then 0.1 g of diethylamine and 0.4 g of TBTU (0-benzo-triazol-1-yl-, N, ', tetramethyluronium tetrafluoroborate) are added and the mixture is stirred for 20 hours. the room temperature. It is then concentrated and the residue is suspended in water and extracted with methylene chloride. The organic phase is concentrated and chromatographed through a column of silica gel with methylene oruro / methanol (19: 1). Yield: 0.2 g (68% of theory), Rf value: 0.36 (silica gel, methylene chloride / ethanol = 9: 1) C30H34N402 mass spectrum: m / z = 482 (M +) Analogously to Example 6 the following compounds are prepared: (1) 3-Z- [1- (4- (piperidin-methyl) -phenylamino) -1-methyl-methylene] -2-indolinone-5-diethylcarbamoyl-2-indolinone Prepared from of the compound prepared according to Example 5 (1) and diethylamine. C27H34N402 mass spectrum: m / z = 446 (M +) (2) 3-Z- [l- (4- (N-met lN-methylsulfonyl-a-ino) -phenylamino) -1-methyl-methylene] -2 -indolinone-5-di et ilcarbamo i 1 -2-indole inona Prepared from the compound prepared according to Example 5 (4) and diethylamine. C23H28N40lS mass spectrum: m / z = 457 (M + H +) (3) 3-Z- [1- (4 - (2, 3, 4, 5-tetrahydro-benzo (d) azepin-3-yl-methyl ) -phenylamino) -1-methyl-ethylene] -5-diethylcarbamoyl-2-indolinone (4) 3-Z- [l- (4- (2,3,4,5-tetrahydro-benzo (d) azepin-3) -yl-methyl) -phenylamino) -1-methyl-methylene] -5-dimethylcarbamoyl-2-indolinana (5) 3-Z- [1- (4- (N-phenylmethyl-N-methylamino-methyl) -phenylamino) -1-methyl-methylene] -5-methylcarbamoyl-2-lindolinone (6) 3-Z- [1- (4- (N-phenylmethyl-N-methylamino-methyl) -phenylamino) -1-methyl-methylene] - 5-dimethyl-c a rb amo i 1 - 2 - i ndo 1 inona (7) 3-Z- [1- (4- (N-phenylmethyl-N-methylamino-methyl) -phenylamino) -1-methyl-methylene ] -5-diethyl-ca rb amo i 1 - 2 - i ndo 1 inona (8) 3-Z- [1- (4- (N-phenylmethyl-N-methylamino-methyl) -phenylamino) -1-methyl- methylene] -5-propyl-carbamoyl-2-indolinone (9) 3-Z- [1- (4- (N-phenylmethyl-N-methylamino-methyl) -phenylamino) -1-methyl-methylene] -5-dipropyl- carbamoyl-2-indolinone (10) 3-Z- [1- (4- (dimethylamino-methyl) -phenylamino) -1-methyl-methylene] -5-me Tilcarbamoyl-2-indolinone (11) 3-Z- [l- (4- (dimethylamino-methyl) -phenylamino) -1-methyl-methylene] -5-dimethylcarbamoyl-2-indolinone (12) 3-Z- [l - (4- (dimethylamino-metll) -phenylamino) -1-methyl-methylene] -5-diethylcarbamoyl-2-indolinone (13) 3-Z- [1- (4- (dimethylamino-methyl) -phenylamino) -1 -methyl-methylene] -5-propylcarbamoyl-2-indolinone (14) 3-Z- [1- (4- (dimethylamino-methyl) -phenylamino) -1-methyl-methylene] -5-dipropyl-carbamoyl-2- indolinone (15) 3-Z- [1- (3- (dimethylamino-methyl) -phenylamino) -1-methyl-methylene] -5-methylcarbamoyl-2-indolinone (16) 3-Z- [1- (3- (dimethylamino-methyl) -phenylamino) -1-methyl-methylene] -5-dimethylcarbamoyl-2-indolinone (17) 3-Z- [1- (3- (dimethylamino-methyl) -phenylamino) -1-methyl-methylene ] -5-dimethylcarbamoyl-2-indolinone (18) 3-Z- [1- (3- (dimethylamino-methyl) -phenylamino) -1-methyl-methylene] -5-propylcarbamoyl-2-indolinone (19) 3- Z- [1- (3- (dimethylamino-methyl) -phenylamino) -1-methyl-methylene] -5-dipropyl-carbamoyl-2-indolinone (20) 3-Z- [1- (4-chloro-phenylamino) -l-methyl-methylene] -5- methylcarbamoyl-2-indolinone (21) 3-Z- [1- (4-chloro-phenylamino) -l-methyl-methylene] -5-dimethylcarbamoyl-2-indolinana (22) 3-Z- [1- (4- chloro-phenylamino) -l-methyl-methylene] -5-diethyl-carbamoyl-2-indolinone (23) 3-Z- [1- (4-chloro-phenylamino) -l-methyl-methylene] -5-propyl-carbamoyl- 2-indolinone (24) 3-Z- [1- (4-chloro-phenylamino) -l-methyl-methylene] -5-dipropyl-carbamoyl-2-indolinone (25) 3-Z - (1-phenylamino-l- methyl-methylene) -5-methylcarbamoyl-2-lindolinone (26) 3 -Z - (1-phenylamino-1-methyl-methylene) -5-dimethylcarbamoyl-2-indolinone (27) 3-Z - (1-phenylamino-1) -methyl-methylene) - 5-diethylcarbamoyl-2-indolinone Example 7 3-Z- l- (4-methyl-3-amino-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone 130 mg of 3-Z - [1 - ( 4-methyl 1- (3-nitro-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone are dissolved in 9 ml of methanol and hydrogenated with 50 mg of Raney nickel at room temperature and at a pressure of hydrogen of 3 bars. The catalyst is filtered off and the solution is concentrated. Yield: 97 mg (70% of theory), Rf value: 0.60 (silica gel, methylene chloride / ethanol = 4: 1) C? 8H? 8N402 mass spectrum: m / z = 322- (M +) Analogously to Example 7, the following compound is prepared: (1) 3-Z - [1- (4-piperidino-methyl) -3-amino-phenylamino) -1-methyl-methylene] -5-amido-2-indolinone Prepared starting from 3-Z - [1 - (4-p ipe ri dino-methyl) -3-nitro-phenylamino) -1-methyl-methylene] - 5 -amido-2-indolinone Rf value: 0.15 (gel of silica, methylene chloride / ethanol 9: 1) C23H27N5? 2 mass spectrum: m / z = 406 (M + H +) E xemple 8 Dry ampoule with 75 mg of active ingredient per 10 ml Compound: Active ingredient 75.0 mg Mannitol 150.0 mg Water for injection purposes up to 10.0 ml Preparation: The active principle and mannitol dissolve in water. After filling, it is lyophilized. The solution to give the ready-to-use solution is made with water for injection purposes.

Example 9 Dry ampule with 35 mg of active ingredient per 2 ml Compound: Active ingredient 35.0 mg Mannitol 100, 0 mg Water for injection purposes up to 2.0 ml Preparation: The active principle and mannitol dissolve in water. After filling, it is lyophilized. The solution to give the ready-to-use solution is made with water for injection purposes.

Example 10 Tablet with 50 mg of active ingredient Composition: (1) Active ingredient 50.0 mg (2) Lactose 98.0 mg (3) Corn starch 50.0 mg 4) Polyvinyl pyrrolidone 15.0 mg 5) Magnesium stearate 2.0 mq 215.0 mg Preparation: (1), (2) and (3) are mixed and granulated with an aqueous solution of (4). The dried granulate is added by mixing (5). Compressed, biplanes, faceted on both sides and dividing notch on one side are pressed from this mixture. Diameter of the tablets: 9 mm.

E xemplo 11 Tablet with 350 mg of active ingredient Composition: (1) Active ingredient 350.0 mg (2) Lactosal 36.0 mg (3) Corn starch 80.0 mg (4) Polyvinyl pyrrolidone 30.0 mg (5) ) Magnesium stearate 4.0 mg 600.0 mg Preparation: (1), (2) and (3) are mixed and granulated with an aqueous solution of (4). The dried granulate is added by mixing (5). Compressed, biplanes, faceted on both sides and dividing notch on one side are pressed from this mixture. Diameter of the tablets: 12 mm.

Example 12 Capsules with 50 mg of active ingredient Compound: (1) Active ingredient 50.0 mg (2) Dried corn starch 58.0 mg (3) Powdered lactose 2.0 mg (4) Magnesia stearate 50.0 mg 160 , 0 mg Preparation: (1) is mixed by grinding with (3). This ground mixture is added, under intensive mixing, to the mixture based on (2) and (4). This powder mixture is introduced into a capsule filling machine in hard gelatin plug-in size 3 capsules.

E xemployment 13 Capsules with 350 mg of active ingredient Compo sition: (1) Active ingredient 350.0 mg (2) Dried corn starch 46.0 mg (3) Powdered lactose 30.0 mg (4) Magnesia stearate 4 , 0 mg 430.0 mg Preparation: (1) is mixed by grinding with (3). This crushed mixture is added, under intense mixing, to the mixture based on (2) and (4). This powder mixture is introduced into a capsule filling machine in hard gelatin plug-in capsules of size 0. E xample 14 Suppositories with 100 mg of active ingredient 1 suppository contains: Active ingredient 100.0 mg Polyethylene glycol (MW 1500) 600, 0 mg Polyethylene glycol (MW 6000) 460.0 mg Polystyrene monostearate 1 in orbit 840.0 mg 600.0 mg Preparation: Polyethylene glycol is fused together with polystyrene monostearate 1 in soy. At 40 ° C, the milled active substance is dispersed homogeneously in the melt. It is cooled to 38 ° C and poured into weakly cooled suppository molds beforehand.

Claims (13)

CLAIMS Substituted indolinones of the general formula wherein X means an oxygen or sulfur atom, Ri means a hydrogen atom, a C 1 -C-alkoxycarbonyl or C 2-4 alkanoyl group, R 2 means a carboxy or C 4 -C 4 -alkoxy group, or a aminocarbonyl group optionally substituted with one or two C? _3 alkyl groups, wherein the substituents may be the same or different, R means a hydrogen atom or a Cl-6 alkyl group which, from the 2-position referred to the carbon of the group R3-C (R4NR5) =, may be substituted with a fluorine, chlorine or bromine atom, with a hydroxy group, C1-3 alkoxy, alkyl C? -3-sui phenyl, alkyl C? -3-sulf Inyl, C C-3-sulfonyl alkyl, phenyl 1 s, phenyl, 1-phenyl, phenylsulfonyl, amino, C ?3-amino alkyl, di- (C C3 alkyl) -amino , C2-5-aminoalkanoyl or N- (C1-3alkylamino) - a1Cy an1C2-5_amino, R4 means a hydrogen atom, a C1-6 alkyl group or a C5_7 cycloalkyl group optionally substituted with a group at C 1 -C 3, in which a methylene group in the 3 or 4 position, referred to the carbon atom of the group R 3 -C (R 4 NR 5) =, can be substituted with an imino group optionally substituted with a C 3 - 3 alkyl group, a phenyl or naphthyl group, which may be substituted with a fluorine, chlorine, bromine or iodine atom, with a methoxy group, optionally substituted with 1 to 3 fluorine atoms, with a C2-3 alkoxy group, in position 2 or 3, it can be substituted with an alkyl group C? _3-amino, di- (C3_3 alkyl) -amino or cycloalkyleneimino of 5 to 7 members, wherein, in each case, additionally an alkyl part in the alkylamino groups and The aforementioned dialkylamino can be substituted with a phenyl group, with a trifluoromethyl, amino, C alqu-3-amino alkyl, di- (C C _3) alkyl- amino, C2-s-amino-alkanoyl, N- (C-alkyl) group. ? _3) - at 1 cano i 1 C2-5- amino, C1-5 alkyl- s ul f on i 1 ami no, N- (C 1 - 3 alkyl) -alkyl C 1-5 - su 1 fo or 1 ami no, feni 1 its 1 f on i 1 ami no, N- (C 1-3 alkyl) -phenyl-sulphonylamino, aminosulfonyl, alkyl C 3-aminosulphonyl or di- (C 1 -C 3 alkyl) -aminosulfonyl, where, in each case, additionally an alkyl part in the aforementioned alkylamino and dialkylamino groups can be substituted with a phenyl group, with a carbonyl group, which is substituted by a hydroxy group, C? _3 alkoxy, amino, C? -3 alkyl -amino or N- (C 1-5 alkyl) -alkyl C 3 -amino, wherein, in each case, additionally an alkyl part in the groups mentioned above may be substituted with a carboxy, alkoxy group C.sub.3 - ca.sub.1 or phenyl or, in position 2 or 3, with a di- (Ci.sub.3) -amino, piperazino, N- (C.sub.C.sub.3.sub.3) -pipene or cycloalkyleneimino group. to 7 members, with a C? -3 alkyl group, which is substituted with an amino group, C? -7-amino alkyl, Cs-7-amino-cycloalkyl or C? _3-amino phenylalkyl, which in each case may be substituted additionally at the nitrogen atom with a C 1-3 alkyl group, in which the hydrogen atoms are replaced, partially or completely, by fluorine atoms, with a C 5-7 cycloalkyl group, C 2-4 alkenyl or C 1 alkyl 4, wherein the above-mentioned C s _4 alkyl substitute may in each case be further substituted with a cyano, carboxy, C 1 -C 3 alkoxy, pyridyl, imidazolyl, ben zo [1] group. 3] di oxc 1 or phenyl, the phenyl group being mono-, di- or tri-substituted with fluorine, chlorine or bromine atoms, with a methyl, methoxy, trifluoromethyl, cyano or nitro, and the substituents may be the same or different, or it may be substituted in position 2, 3 or 4 with a hydroxy group, with a C? _3 alkyl group which may be substituted with a hydroxy, carboxy, thi group or group 1 Inno, 1 - ox i do - ti omo rfo 1 i no, 1,1-di x i do - ti omo rfo lino, piperazino, N- (alkyl C? _3) -piperazino or N-feni 1 -p ipe razino, with a cycloalkyleneimino group of 5 to 7 members or with a cycloalkyleneimino group of 4 to 7 members, wherein the cycloalkyleneimino groups of 5 to 7 members mentioned above may be substituted with one or two C?-3 alkyl groups, with one group C5-7 cycloalkyl or phenyl, with a C 1-3 alkyl, C 5-7 cycloalkyl, phenyl, carboxy or C 1-4 alkoxycarbonyl group with a hydroxy group, and in the aforementioned cycloalkyleneimino groups a methylene group contiguous with Nitrogen atom can be replaced by a carbonyl group, with a C3_3 alkyl group, which is substituted with a cycloalkyleneimino group of 5 to 7 members, being condensed to the aforementioned cycloalkyleneimino groups of 5 to 7 members, through contiguous carbon atoms, a phenyl group optionally mono- or di-substituted with fluorine, chlorine or bromine atoms, with methyl or methoxy groups, the substituents being the same or different, or a group or oxazolo, imidazolo, thiazolo, pyridino, pyrazino or pyrimidino optionally substituted with a methyl, methoxy or amino group, the substituted phenyl groups, previously mentioned, having a fluorine, chlorine or bromine atom, may be further substituted with a methyl, methoxy or nitro group, a 5-membered heteroaromatic group, containing an imino group, an oxygen or sulfur atom, or an imino group, an oxygen or sulfur atom and one two nitrogen atoms, a heteroaromatic group of 6 members, which contains one, two or three nitrogen atoms, wherein the above-mentioned 5 and 6 membered heteroaromatic groups can be further substituted with a chlorine or bromine atom or with a methyl group, or with the heteroaromatic groups of 5 and 6 repreferably mentioned members can be condensed a phenyl ring through 2 contiguous carbon atoms, and R5 means a hydrogen atom or an alkyl group or C? _3, the carboxy, amino or imino groups present with separable radicals in vivo, their isomers and their salts may be substituted. 2. Substituted indolinones of the general formula 1 according to claim 1, wherein X means an oxygen atom, Ri means a hydrogen atom, R2 means an aminocarbonyl group, R3 means a hydrogen atom or a C1-4 alkyl group which, from position 2 referred to the carbon atom of the group R3-C (R4NR5) =, may be substituted with a chlorine or bromine atom or with a group phenylsulfonyl, R 4 means a hydrogen atom, a C 1 -C 3 alkyl group or a cyclopentyl or cyclohexyl group, optionally substituted with a methyl group, wherein in the cyclopentyl and cyclohexyl group a methylene group in the 3 or 4 position, referred to carbon atom of the group R -C (R4NR5) =, may be replaced by an imino group occasionally substituted with a methyl group, a phenyl group, which may be substituted by a fluorine, chlorine, bromine or iodine atom, with nn methoxy group, optionally substituted with 1 to 3 fluorine atoms, with a C3 alkoxy group which, in position 2 or 3, can be substituted with a methylamino, dimethylamino or cycloalkyleneimino group of 5 to 7 members, wherein, in each In addition, a methyl group in the above-mentioned amino groups can be substituted with a phenyl group, with a trifluoromethyl, amino, C2-5-amino-alkanoyl, N- (C1-3-alkyl) -C2-5-aminoalkanoyl, C5-5 alkyl-1-amino 1 ami no, N- (alkyl C? _3) - a 1 qui 1 C1-5-s ul f oni lamino, feni 1 su 1 f on i 1 ami no, N- (C1-3 alkyl) -f eni 1 its 1-onylamino or aminosulfonyl, wherein, in each case, additionally an alkyl part in the aforementioned alkylamino and dialkylamino groups can be substituted with a phenyl group, with a carbonyl group, which is substituted with a hydroxy group, alkoxy C ? 3, amino, C? _3-amino alkyl or N- (C 1-5 alkyl)-C? -3-amino alkyl, wherein, in each case, an alkyl part of the groups mentioned above can be further substituted with a carboxy group, C1-3 alkoxy -carbonyl or phenyl or, in position 2 or 3, with a di- (C1-3 alkyl) -amino, piperazino, N- (C1-3 alkyl) -piperazino group or cycloalkyleneimin or from 5 to 7 members, with a C1-3 alkyl group, which is substituted with an amino group, C1-.7-alkylamino, C5_7-amino cycloalkyl or phenyl-C? -3-amino alkyl, which in each case can be further substituted in the atom, with nitrogen with a C? _3 alkyl group, in which the hydrogen atoms are replaced, partially or completely, by fluorine atoms, with a cyclohexyl group, C2- alkenyl or C1 alkyl -4, wherein the above-mentioned C? -4 alquilo alkyl substituent can each be additionally substituted with a cyano, carboxy, C1-3 alkoxy- ca rb oni 1, pyridyl, imidazolyl, ben zo [1, 3] group di oxo 1 or phenyl, the phenyl group being unsubstituted with a fluorine, chlorine or bromine atom, with a methyl, methoxy, cyano, trifluoromethyl or nitro group, or di-substituted with fluorine, chlorine or bromine, with methyl or methoxy groups, and the substituents may be the same or different, or may be substituted ion 2, 3 or 4 with a hydroxy group, with a C1-3 alkyl group which may be substituted with a hydroxy, carboxy, thi or rfo 1 i, no, 1-oxide-thiomorpholino, 1,1-dioxido-thiomorpholino group, piperazino, N- (C 1 -) alkylpiperazino or N-pheni 1 -piperazino, with a cycloalkyleneimino group of 5 to 7 members or with a cycloalkyleneimino group of 4 to 7 members, wherein the cycloalkyleneimino groups of to 7 members mentioned above may be substituted with one or two C? _3 alkyl groups, with a cyclohexyl or phenyl group, with a C?-3 alkyl, cyclohexyl, phenyl, carboxy or C-4-4 alco-alkoxycarbonyl group and with a group hydroxy, and in the aforementioned cycloalkyleneimino groups a methylene group contiguous to the nitrogen atom can be replaced by a carbonyl group, with a C? _3 alkyl group, which is substituted with a cycloalkyleneimino group of 5 to 7 members, being condensed to the Cycloalkyleneimino groups of 5 to 7 members precedent mentioned above, through 2 contiguous carbon atoms, a phenyl group optionally mono- or di-substituted with fluorine, chlorine or bromine atoms, with methyl or methoxy groups, the substituents being the same or different, or a pyrazine or thiazolo group optionally substituted with an amino group, it being possible for the mono-substituted phenyl groups mentioned above to be further substituted with a fluorine, chlorine or bromine atom, with a methyl, methoxy or nitro group, a pyridyl group, optionally substituted with a chlorine or bromine atom or with a methyl group, an oxazolyl, isoxazolyl, imidazolyl or thiazolyl group optionally substituted with a methyl group, to which a phenyl ring may be condensed through 2 adjacent carbon atoms, and R5 means a hydrogen atom or an alkyl group C1 -3, its isomers and its salts. 3. Substituted indolinones of the general formula I according to claim 1 or 2, wherein R2 is in the 5-position, its isomers and its salts. 4. Substituted indolinones of the general formula I according to claim 1, in which X is an oxygen atom, Ri is a hydrogen atom, R 2 is an aminocarbonyl group in the 5-position, R 3 is a hydrogen atom or a group C alquilo alkyl which in terminal position can be substituted with a chlorine or bromine atom or with a phenylsulfonyl group, R 4 signifies a hydrogen atom, a C? _3 alkyl group or a cyclopentyl or cyclohexyl group optionally substituted with a methyl group, wherein in the cyclohexyl group a methylene group in the 4-position, referred to the carbon atom of the group R 3 -C (R 4 NR 5) =, can be replaced by an imino group, optionally substituted with a methyl group, a phenyl group, which may be substituted with a fluorine, chlorine, bromine or iodine atom, with a methyl or ethyl group, which in each case is substituted with a C 1 _ 3-amino alkyl, di- (C 1-3 alkyl) amino group, ti omo rfo 1 i no, 1 - óx i I do not know, 1,1-dioxido- ti omo rfolino, N-phenyl-piperazino, ci c 1 oal queni 1 enimino of 5 to 6 members or with a cycloalkyleneimino group of 5 to 7 members, the cycloalkyleneimino groups of 5 to 7 members mentioned above having one or two methyl groups, with a cyclohexyl or phenyl group, with a methyl, cyclohexyl or phenyl group, and with a hydroxy group, or with a methyl or ethyl group, can be substituted. which can be substituted in each case with a phenyl group which is substituted with a cycloalkyleneimino group of 5 to 7 members, being condensed to the aforementioned cycloalkyleneimino groups, through 2 contiguous carbon atoms, additionally a phenyl ring, with a a methyl or ethyl group, which is substituted by an amino, methylamino or ethylamino group which, in each case, is additionally substituted at the nitrogen atom of the amine with a benzyl or phenylethyl group, and may be mono substituted. phenyl of the groups mentioned above in each case with a fluorine, chlorine or bromine atom, with a methyl, methoxy, cyano, trifluoromethyl or nitro group, or di-substituted with fluorine, chlorine or bromine atoms, with methyl or methoxy groups, and the substituents thereof may be the same or different, wherein additionally the above-mentioned phenyl groups may be substituted with a fluorine, chlorine or bromine atom, with a methyl, methoxy or nitro group, and R5 means a hydrogen atom or a C1-4 alkyl group, its isomers and its salts. 5. Substituted indolinones of the general formula I according to claim 1, wherein X means an oxygen atom, Ri means a hydrogen atom, R2 means an aminocarbonyl group in the 5-position, R3 means a hydrogen atom or a group alkyl C? _4, R4 means a phenyl group which may be substituted with a fluorine, chlorine, bromine or iodine atom, with a methyl or ethyl group, which in each case is substituted with an alkyl C? _3-amino group, di - (alkyl C 1 _3) - ami no, as a follicle, 1-oxo-doo-1-oxo, 1,1-dioxido-thiomorpholino, N-phenyl-piperazino, cyc 1 or 1 quen i 1 enimi, not from 5 to 6 members or with one group cycloalkyleneimino of 5 to 7 members, the cycloalkyleneimino groups of 5 to 7 members mentioned above having one or two methyl groups, with a cyclohexyl or phenyl group, with a methyl, cyclohexyl or phenyl group, and with a hydroxy group, or with a methyl or ethyl group, which may be substituted in each case with a phenyl group which is substituted at the 4 position with a cycloalkyleneimino group of 5 to 7 members, being condensed to the aforementioned cycloalkyleneimino groups, through 2 contiguous carbon atoms, additionally a phenyl ring, with a methyl or ethyl group, which they are substituted with an amino, methylamino or ethylamino group which, in each case, is additionally substituted on the nitrogen atom of the amine with a benzyl group, and in which the phenyl part can be mono-substituted with a fluorine atom. , chlorine or bromine, with a methyl, methoxy, cyano, trifluoromethyl or nitro group, or substituted with methyl or methoxy groups or substituted with methyl or methoxy groups, and the substituents may be the same or different, wherein additionally the monomeric phenyl groups mentioned above can be substituted with a fluorine, chlorine or bromine atom, with a methyl, methoxy or nitro group, and R5 means a tome hydrogen or C1-4 alkyl, their isomers and salts group. 6. The following substituted indolinones of the general formula I according to claim 1: (a) 3-Z - [1 - (4-p ipe ri di nome ti 1 - f eni 1 ami no) - 1 -me ti 1 - me ti 1 in] - 5 - ami do - 2 - i ndo 1 i nona, (b) 3-Z- [l- (4-bromo-phenylamino) -1-methyl-methylene] -5-amido-2- indolinone, (c) 3 - Z - [1 - (4-p ipe ri di nome ti 1 -phenylamino) -1-butyl-methylene] -5-amido-2-indolinone, (d) 3-Z - [1 - (4-chloro-f eni lamino) - 1 -me ti 1 -me ti len] - 5 -ami do - 2 - i ndo 1 i nona and (e) 3 - Z - (1 - pheni 1 ami nome ti 1 en] -5-amido-2-indolinone, (f) 3-Z - [1 - (4 - (N -benzyl-N-methyl-aminomethyl) -phenylamino) -1-methyl-me ti 1 in] - 5-ami do -2-indo 1 inona, (g) 3-Z - [1 - (4 - (N - (4-chlorobenzyl) -aminomethyl) -phenylamino) -1-methyl-me ti 1 in] - 5 - ami do - 2 - indole inona, (h) 3 - Z - [1 - (4 - (-benzyl-N-ethyl-aminomethyl) -phenylamino) -1-methyl-me ti 1 in] - 5 - ami do - 2 - ndol inona, (i) 3 - Z - [1 - (4 - (N -benzyl-amin omethyl) -phenylamino) -1-methyl-methylene] -5-amido-2-lndolinone, (j) 3-Z - [1 - (4 - (N -benz 1-N -methyl-amino-methyl) -phenylamino ) -methylene] -5-amido-2-indolinone, (k) 3-Z- [1- (4 - (2, 3, 4, 5- te t rahidro-benzo (d) azepin-3-yl-methyl) ) -phenylamino) -1-methyl-me ti 1 in] - 5 - ami do - 2 - indo 1 inona, (1) 3-Z- [l- (4-piperidinomethyl-3-nitro-phenylamino) -1- methyl-me ti 1 in] - 5 - ami do - 2 - indo 1 i none and (m) 3 - Z - [l- (4-methyl-3-nitro-phenylamino) -1-methyl-methylene] -5 -amido-2 - i ndo 1 inona, as well as its isomers and its salts. 7. 3-Z- [l- (4- (N-benzyl-N-methyl-aminomethyl) -f in i-amino) -1-methyl-1-methyl-1 in] -5-ami-do-2- in do 1 ino na and its salts. 8. 3-Z- [l- (4- (2,3,4,5-tetrahydro-benzo (d) -azepin-3-yl-methyl) -phenylamino) -

1-methyl-methylene] - 5 -ami do -

2 - indo 1 inona and its salts. 9. Physiologically compatible salts of the compounds according to claims 1 to 8. Medicament containing a compound according to at least one of claims 1 to 8 or a salt according to claim 9 together with optionally one or more support substances and / or inert diluent agents. 11. Use of a compound according to at least one of claims 1 to 8 or a salt according to claim 9 for the preparation of a medicament that is suitable for the treatment of excessive or abnormal cell proliferations. Method for the preparation of a medicament according to claim 10, characterized in that, by non-chemical route, a compound according to at least one of claims 1 to 8 or a salt according to claim 9 is incorporated in one or more support substances and / or inert diluent agents. 13. Process for the preparation of the compounds according to claims 1 to 9, characterized in that a. a compound of the general formula is reacted wherein X and R3 are defined as mentioned in claims 1 to 8R2 'has the meanings mentioned in claims 1 to 8 for R2, Re means a hydrogen atom or a protecting group for the nitrogen atom of the lactam group, which may represent one of the radicals R2' or R? also a bond to a solid phase optionally formed through a spacer, and the other of the radicals R2 'or R has the meanings mentioned above, and Zi means a halogen atom, a hydroxy, alkoxy or aralkoxy group, with an amine of the general formula wherein R 4 and R 5 are defined as mentioned in claims 1 to 8 and, if necessary, then a protective group used for the nitrogen atom of the lactam group or a compound thus obtained is separated from a compound thus obtained. separates from a solid phase, or b. for the preparation of a compound of the general formula I, wherein R 2 represents one of the aminocarbonyl groups mentioned in claims 1 to a compound of the general formula wherein Ri and R to R5 are defined as mentioned in claims 1 to 6, or their reactive derivatives, with an amine of the general formula H - (R7NR8) (V), wherein R7 and Ro, which may be equal or different, they mean hydrogen atoms or C? _3 alkyl groups and if desired, then a compound of the general formula I, thus obtained, which contains an alkoxycarbonyl group, is transformed, by hydrolysis, into a corresponding carboxy compound. , or a compound of the general formula I, thus obtained, containing an amino or alkylamino group, is transformed, by alkylation or reductive alkylation, into a corresponding alkylamino or dialkylamino compound, or a compound of the general formula I, thus obtained , which contains an amino or alkylamino group, is transformed, by acylation, into a corresponding acyl compound, or, a compound of the general formula I, thus obtained, which contains a carboxy group, is transformed, by esterification or amidation, in a corresponding ester or aminocarbonyl compound, or a compound of the general formula I, thus obtained, which contains a nitro group, is transformed, by reduction, into a corresponding amino compound, or if necessary, separates a protective radical used during the reactions for the protection of reactive groups, or a compound of the general formula I, thus obtained, is separated into its stereoisomers, or a compound of the general formula I, thus obtained, is transformed into its salts , in particular for the pharmaceutical application, in their physiologically compatible salts, with an inorganic or organic acid or base.