DE10042696A1 - New 3-(amino-methylene)-2-indolinone derivatives are kinase inhibitors and cell proliferation inhibitors useful e.g. for treating tumors, metastasis, rheumatoid arthritis or psoriasis - Google Patents

Abstract

6-Carboxy-3-(anilino- or cycloalkylamino-methylene)-indolin-2-one or -thione derivatives (I) are new. 6-Carboxy-3-(anilino- or cycloalkylamino-methylene)-indolin-2-one or -thione derivatives of formula (I) and their tautomers, diastereomers, enantiomers (and mixtures) and salts are new. X = O or S; R1 = H or prodrug residue; R2 = COOH, (1-6C) alkoxycarbonyl (optionally substituted (os) terminally by Ph, heteroaryl, COOH, alkoxycarbonyl, CONH2, mono- or dialkylaminocarbonyl or (in the case of (2-6C) alkoxycarbonyl) Cl, OH, alkoxy, NH2 or mono- or dialkylamino), (5-7C) cycloalkoxycarbonyl, arylalkoxycarbonyl, CONH2, CONHMe or ethylaminocarbonyl (os in the 2-position by OH or alkoxy); or di-(1-2C alkyl)-aminocarbonyl if R4 is other than aminosulfonylphenyl or N-(1-5C alkyl)-alkylaminocarbonylphenyl; R3 = H, 1-6C alkyl, 3-7C cycloalkyl, CF3 or heteroaryl; or phenyl or naphthyl (both os by 1 or 2 of halo, CF3, alkyl or alkoxy, and further os by OH, hydroxyalkyl, alkoxyalkyl, CN, carboxyalkyl, alkoxycarbonyl, CONH2, mono- or dialkylaminocarbonyl, NO2, NH2, mono- or dialkylamino, aminoalkyl, alkylcarbonylamino, N-(alkyl)-alkylcarbonylamino, alkylcarbonylaminoalkyl, N-(alkyl)-alkylcarbonylaminoalkyl, alkylsulfonylamino, alkylsulfonylaminoalkyl, N-(alkyl)-alkylsulfonylamino, N-(alkyl)-alkylsulfonylaminoalkyl, arylalkylaminosulfonyl, 4-7C cycloalkylamino, Q, Q-CO-, Q-SO2-, Q-alkyl-, Q-CO-alkyl-, Q-SO2-alkyl-, heteroaryl or heteroarylalkyl); Q = 4-7 membered cycloalkyleneimino (CAI), where CH2 in the 4-position of 6- or 7-membered CAI is optionally replaced by O, S, SO, SO2, NH or N(alkyl); R4 = 3-7C cycloalkyl (in which the CH2 in the 4-position of 6-7 membered cycloalkyl is os by NH2 or mono- or dialkylamino or replaced by NH or N(alkyl)); or phenyl substituted by R6 and further os by 1 or 2 of halo, 1-5C alkyl, CF3, alkoxy, COOH, alkoxycarbonyl, NH2, NHCOMe, alkylsulfonylamino, CONH2, mono- or dialkylaminocarbonyl, SO2NH2, mono- or dialkylaminosulfonyl, NO2 or CN; R6 = e.g. (i) H, halo, CN, NO2, 1-5C alkyl, 3-7C cycloalkyl, CF3, heteroaryl, 2,4-dioxo-imidazolidin-5-ylidenemethyl (os by alkyl on either or both N), alkoxy, alkoxyalkoxy, phenylalkoxy, amino-(2-3C) alkoxy, mono- or dialkylamino-(2-3C) alkoxy, phenylalkylamino-(2-3C) alkoxy, N-(alkyl)-phenylalkylamino-(2-3C) alkoxy, 5-7 membered CAI-(2-3C) alkoxy, alkylthio, COOH, (1-4C) alkoxycarbonyl, CONH2, alkylaminocarbonyl, N-(1-5C alkyl)-alkylaminocarbonyl, phenylalkylaminocarbonyl, N-(alkyl)-phenylalkylaminocarbonyl, piperazinocarbonyl or N-(alkyl)-piperazinocarbonyl; (ii) alkylaminocarbonyl or N-(1-5C alkyl)-alkylaminocarbonyl, in which an alkyl group is substituted by COOH or alkoxycarbonyl or in the 2- or 3-position by di-(2-3C alkyl)-amino, piperazino, N-alkylpiperazino or 4-7 membered CAI; (iii) (3-7C) cycloalkylcarbonyl (in which the CH2 in the 4-position of 6-7 membered cycloalkyl is os by NH2 or mono- or dialkylamino or replaced by NH or N(alkyl)) or (iv) 4-7 membered CAI (in which (a) CH2 groups bonded to the imino can be replaced by CO or SO2, (b) the cycloalkylene part is optionally fused with phenyl, (c) 1 or 2 H can be replaced by alkyl and (d) CH2 in the 4-position of 6- or 7-membered CAI is os by COOH, alkoxycarbonyl, CONH2, mono- or dialkylaminocarbonyl, phenylalkylamino or N-(alkyl)-phenylalkylamino or replaced by O, S, SO, SO2, NH, N(alkyl), N(Ph), N(alkanoyl) or N(benzoyl)); R7 = e.g. (i) 3-7C cycloalkyl (in which the CH2 in the 4-position of 6-7 membered cycloalkyl is os by NH2 or mono- or dialkylamino or replaced by NH or N(alkyl); or in 5-7 membered cycloalkyl (CH2)2 is optionally replaced by CONH, (CH2)3 is optionally replaced by NHCONH or CONHCO or (CH2)4 is optionally replaced by NHCONHCO, where all N atoms are os by alkyl), or (ii) aryl, heteroaryl, OH, alkoxy, NH2, mono- or di-(1-7C alkyl)-amino, NHPh, N-(phenyl)-alkylamino, phenylalkylamino, N-(alkyl)-phenylalkylamino, di-(phenylalkyl)-amino, mono- or di-(w-hydroxy-(2-3C) alkyl)-amino, mono- or di-(w-hydroxy-(2-3C) alkyl)-amino, di-(w-alkoxy-(2-3C) alkyl)-amino, N-(dioxolan-2-yl)-alkylamino, alkylcarbonylamino-(2-3C) alkylamino, alkylcarbonylamino-(2-3C) alkyl-N-(alkyl)-amino, alkylsulfonylamino, N-(alkyl)-alkylsulfonylamino, alkylsulfonylamino-(2-3C) alkylamino, alkylsulfonylamino-(2-3C) alkyl-N-(alkyl)-amino, carboxyalkylamino, N-(alkyl)-carboxyalkylamino or guanidino (os by 1 or 2 alkyl) and R5 = H or alkyl. See DEFINITIONS for 'Full definitions'. An Independent claim is included for the preparation of (I).

Description

The present invention relates to new 6-position substituted indolinones of the general formula

their tautomers, their diastereomers, their enantiomers, their Mixtures and their salts, especially their physiological compatible salts, which have valuable properties.

The above compounds of general formula I, in which R _{1 represents} a hydrogen atom or a prodrug residue, have valuable pharmacological properties, in particular an inhibitory effect on various kinases, especially on receptor tyrosine kinases such as VEGFR2, PDGFRα, PDGFRβ, FGFR1, FGFR3, EGFR, HER2, IGF1R and HGFR, as well as on complexes of CDK's (Cyclin Dependent Kinases) such as CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8 and CDK9 with their specific cyclin (A, B1, B2, C, D1, D2, D3, E, F, G1, G2, H, I and K) and on viral cyclin (see L. Mengtao in J. Virology 71 (3), 1984-1991 (1997)), and on proliferation cultured human cells, especially those of endothelial cells, e.g. B. in angiogenesis, but also on the proliferation of other cells, especially tumor cells.

The other compounds of the above general formula I, in which R ₁ does not represent a hydrogen atom and no prodrug residue, are valuable intermediates for the preparation of the compounds mentioned above.

The present invention thus relates to the above compounds of the general formula I, the compounds in which R _{1 represents} a hydrogen atom or a prodrug residue have valuable pharmacological properties, the medicaments containing the pharmacologically active compounds, their use and process for their preparation position.

In the above general formula I mean
X is an oxygen or sulfur atom,
R _{1 is} a hydrogen atom or a prodrug residue such as a C _1-4 alkoxycarbonyl or C _2-4 alkanoyl group,
R _{2 is} a carboxy group, a linear or branched C _1-6 alkoxy-carbonyl group, a C _4-7 cycloalkoxycarbonyl or an aryloxycarbonyl group,
a linear or branched C _1-6 -alkoxy-carbonyl group which is terminated in the alkyl part by a phenyl, heteroaryl, carboxy, C _1-3 -alkoxy-carbonyl, aminocarbonyl, C _1-3 -alkylamino-carbonyl- or di (C _1-3 alkyl) aminocarbonyl group is substituted,
a linear or branched C _2-6 alkoxy carbonyl group which is terminated in the alkyl part by a chlorine atom or a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _{1- 3} alkyl) amino group is substituted,
an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group which is optionally substituted in the 2-position of the ethyl group by a hydroxy or C _1-3 alkoxy group or, if R _{4 is} not aminosulfonylphenyl or N- (C _1-5 alkyl) - C Represents _1-3 alkylaminocarbonylphenyl group, also a di (C _1-2 alkyl) aminocarbonyl group,
R _{3 is} a hydrogen atom, a C _1-6 alkyl, C _3-7 cycloalkyl, trifluoromethyl or heteroaryl group,
a phenyl or naphthyl group, one by a fluorine, chlorine, bromine or iodine atom, by a trifluoromethyl, C _1-3 alkyl or C _1-3 alkoxy group mono- or disubstituted phenyl or naphthyl group, in which In the case of disubstitution, the substituents may be the same or different and where the unsubstituted as well as the mono- and disubstituted phenyl and naphthyl groups mentioned above
by a hydroxy, hydroxyC _1-3 alkyl or C _1-3 alkoxyC _1-3 alkyl group,
by a cyano, carboxy, carboxyC _1-3 alkyl, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino carbonyl or di (C _1-3 alkyl) aminocarbonyl group ,
through a nitro group,
by an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or amino C _1-3 alkyl group,
by a C _1-3 alkylcarbonylamino, N- (C _1-3 alkyl) -C _1-3 alkyl kylcarbonylamino, C _1-3 alkylcarbonylamino C _1-3 alkyl, N- (C _{1 -3-} alkyl) -C _1-3 -alkylcarbonylamino-C _1-3 -alkyl-, C _1-3 -alkyl sulfonylamino-, C _1-3 -alkylsulfonylamino-C _1-3 -alkyl-, N- (C _{1 -3-} alkyl) -C _1-3 -alkylsulfonylamino-C _1-3 -alkyl- or aryl-C _1-3 -alkylsulfonylamino group,
by a Cycloalkylamino-, Cycloalkylenimino-, Cycloalkyleniminocarbonyl-, Cycloalkylenimino-C _1-3 -alkyl-, Cycloalkyleniminocarbonyl-C _1-3 -alkyl- or Cycloalkyleniminosulfonyl-C _1-3 -alkyl group each with 4 to 7 ring, whereby each the methylene group in position 4 in a 6- or 7-membered cycloalkyleneimino group can be replaced by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH or -N (C _1-3 -alkyl) group,
or can be substituted by a heteroaryl or heteroarylC _1-3 alkyl group,
R _{4 is} a C _3-7 cycloalkyl group,
wherein the methylene group in position 4 of a 6- or 7- membered cycloalkyl group is substituted by an amino, C _1-3 -alkylamino or di- (C _1-3 -alkyl) -amino group or by an -NH- or -N (C _1-3 alkyl) group can be replaced,
or a phenyl group substituted by the group R ₆ , which is additionally substituted by fluorine, chlorine, bromine or iodine atoms, by C _1-5 alkyl, trifluoromethyl, hydroxy, C _1-3 alkoxy, carboxy, C _1-3 alkoxycarbonyl, amino, acetylamino, C _1-3 alkyl sulfonyl amino, aminocarbonyl, C _1-3 alkyl aminocarbonyl, di (C _1-3 alkyl) aminocarbonyl, aminosulfonyl, C _1-3 alkylaminosulfonyl, di (C _1-3 alkyl) aminosulfonyl, nitro or cyano groups may be mono- or disubstituted, where the substituents may be the same or different and in which
R _{6 is} a hydrogen, fluorine, chlorine, bromine or iodine atom,
a cyano, nitro, amino, C _1-5 alkyl, C _3-7 cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl group,
the group of the formula

in which the hydrogen atoms bonded to a nitrogen atom can each be replaced independently of one another by a C _1-3 alkyl group,
a C _1-3 alkoxy group, a C _1-3 alkoxy C _1-3 alkoxy, phenyl C _1-3 alkoxy, amino C _2-3 alkoxy, C _1-3 alkylamino -C _2-3 -alkoxy-, di- (C _1-3 -alkyl) -amino-C _2-3 -alkoxy-, phenyl-C _1-3 -alkylamino- C _2-3 -alkoxy-, N- ( C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino-C _2-3 -alkoxy-, C _5-7 -cycloalkylenimino-C _2-3 -alkoxy- or C _1-3 -alkylmercapto group,
a carboxy-, C _1-4 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylamino-carbonyl-, N- (C _1-5 -alkyl) -C _1-3 -alkylaminocarbonyl-, phenyl-C _{1 -3-} alkylamino-carbonyl-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -al kylamino-carbonyl-, piperazinocarbonyl or N- (C _1-3 -alkyl) -pi perazinocarbonyl group,
a C _1-3 -alkylaminocarbonyl- or N- (C _1-5 -alkyl) -C _1-3 -al kylaminocarbonyl group, in which an alkyl part by a car boxy or C _1-3 -alkoxycarbonyl group or in 2- or 3 Position is substituted by a di- (C _1-3 alkyl) amino, piperazino, N- (C _1-3 alkyl) piperazino or a 4- to 7-membered cycloalkyleneimino group,
a C _3-7 cycloalkyl carbonyl group,
wherein the methylene group in position 4 of the 6- or 7- membered cycloalkyl part is substituted by an amino, C _1-3 -alkylamino or di- (C _1-3 -alkyl) -amino group or by an -NH- or -N (C _1-3 alkyl) group can be replaced,
a 4- to 7-membered cycloalkyleneimino group in which a methylene group linked to the imino group can be replaced by a carbonyl or sulfonyl group or
the cycloalkylene part can be condensed with a phenyl ring or
one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group or / and
each the methylene group in position 4 of a 6- or 7- membered cycloalkyleneimino group by a carboxy-, C _1-3 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocar bonyl-, di- (C _1-3 -alkyl) - aminocarbonyl, phenyl-C _1-3 alkyl amino or N- (C _1-3 alkyl) phenyl-C _1-3 alkylamino group or
through an oxygen or sulfur atom, through a sul finyl, sulfonyl, -NH,, -N (C _1-3 alkyl) -, -N (phenyl) -, N (C _1-3 alkyl carbonyl) - or -N (benzoyl) group can be replaced,
a C _1-4 alkyl group substituted by the group R ₇ , where
R _{7 is} a C _3-7 cycloalkyl group,
wherein the methylene group in position 4 of a 6 or 7-membered cycloalkyl group is substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or by an -NH- or -N (C _1-3 alkyl) group can be replaced or
in a 5- to 7-membered cycloalkyl group a - (CH ₂ ) ₂ group can be replaced by a -CO-NH group, a - (CH ₂ ) ₃ group by a -NH-CO-NH- or - CO-NH-CO group can be replaced or a - (CH ₂ ) ₄ group can be replaced by a -NH-CO-NH-CO group, where in each case a hydrogen atom bound to a nitrogen atom is replaced by a C _{1- 3} alkyl group can be replaced
an aryl or heteroaryl group,
a hydroxy or C _1-3 alkoxy group,
an amino, C _1-7 alkylamino, di (C _1-7 alkyl) amino, phenylamino, N-phenyl-C _1-3 -alkyl-amino-, phenyl-C _1-3 - alkyl amino, N- (C _1-3 alkyl) phenylC _1-3 alkylamino or di (phenylC _1-3 alkyl) amino group,
a ω-hydroxy-C _2-3 -alkyl-amino-, N- (C _1-3 -alkyl) -ω-hy droxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _{2 -3-} alkyl) -amino-, di- (ω- (C _1-3 -alkoxy) -C _2-3 -alkyl) -amino- or N- (dioxolan-2-yl) -C _1-3 - alkyl amino group,
a C _1-3 -alkylcarbonylamino-C _2-3 -alkylamino- or C _1-3 -alkylcarbonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
a C _1-3 alkylsulfonylamino, N- (C _1-3 alkyl) -C _1-3 alkylsulfonylamino, C _1-3 alkylsulfonylaminoC _2-3 alkylamino or C _1-3 Alkylsulfonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
a hydroxycarbonyl-C _1-3 -alkylamino or N- (C _1-3 -alkyl) -hydroxycarbonyl-C _1-3 -alkyl-amino group,
a guanidino group in which one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group,
a group of the formula

-N (R ₈ ) -CO- (CH ₂ ) _n -R ₉ (II),

in the
R _{8 is} a hydrogen atom or a C _1-3 alkyl group,
n one of the numbers 0, 1, 2 or 3 and
R _{9 is} an amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino, N- (C _1-4 alkyl) benzylamino or C _1-4 alkoxy group, a 4- to 7-membered cycloalkyleneimino group, the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group being substituted by an oxygen or Sulfur atom, through a sulfinyl, sulfonyl, -NH, -N (C _1-3 alkyl) -, -N (phenyl) -, -N (C _1-3 alkyl carbonyl) - or -N (Benzoyl) group can be replaced, or, if n represents one of the numbers 1, 2 or 3, also represent a hydrogen atom,
a group of the formula

-N (R ₁₀ ) - (CH ₂ ) _m - (CO) _o -R ₁₁ (III),

in the
R _{10 is} a hydrogen atom, a C _1-3 alkyl group, a C _1-3 alkylcarbonyl, arylcarbonyl, phenyl C _1-3 alkylcarbonyl, C _1-3 alkylsulfonyl, arylsulfonyl or phenyl-C _1-3 alkylsulfonyl group,
m one of the numbers 1, 2, 3 or 4,
o the number 1 or, if m is one of the numbers 2, 3 or 4, also the number 0 and
R _{11 is} an amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino, N- (C _1-4 alkyl) benzylamino, C _1-4 alkoxy or C _1-3 alkoxy-C _1-3 alkoxy group, a di optionally substituted in the 1-position by a C _1-3 alkyl group - (C _1-4 -Alkyl) -amino-C _1-3 alkylamino group or a 4- to 7-membered cycloalkyleneimino group, where the cycloalkylene part can be condensed with a phenyl ring or the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group through an oxygen or sulfur atom, through a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl) -, -N (phenyl) -, -N (C _{1- 3} -alkyl-carbonyl) - or -N (benzoyl) group may be replaced,
a C _4-7 cycloalkylamino, C _4-7 cycloalkyl-C _1-3 alkylamino or C _4-7 cycloalkenylamino group in which position 1 of the ring is not involved in the double bond and wherein the groups mentioned above can each additionally be substituted on the amine nitrogen atom by a C _5-7 -cycloalkyl, C _2-4 -alkenyl or C _1-4 -alkyl group,
a 4- to 7-membered cycloalkyleneimino group in which
the cycloalkylene part with a phenyl group or with an oxazolo, imida optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, C _1-3 alkyl, C _1-3 alkoxy or amino group zolo, thiazolo, pyridino, pyrazino or pyrimidino group can be condensed or / and
one or two hydrogen atoms can each be replaced by a C _1-3 alkyl, C _5-7 cycloalkyl or phenyl group or / and
the methylene group in position 3 of a 5-membered cycloalkyleneimino group may be substituted by a hydroxy, hydroxy c _1-3 alkyl, C _1-3 alkoxy or C _1-3 alkoxy-C _1-3 alkyl group can, in each case the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group by a hydroxy, hydroxy-C _1-3 -alkyl-, C _1-3 -alkoxy-, C _1-3 -alkoxy-C _1-3 alkyl, carboxy, C _1-4 alkoxycarbonyl, amino carbonyl, C _1-3 alkylaminocarbonyl, di (C _1-3 alkyl) aminocarbonyl, phenyl C _1-3 -alkylamino or N- (C _1-3 alkyl) phenyl-C _1-3 alkylamino group substituted or
by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 alkyl -) -, -N (phenyl) -, -N (phenyl-C _1-3 alkyl) -) -, -N (C _1-3 -Alkyl-carbonyl -) -, -N (C _1-4 -Hydroxy-carbonyl -) -, -N (C _1-4 -alkoxy-carbonyl -) -, -N (benzoyl -) - or -N (phenyl-C _1-3 alkylcarbonyl -) - group can be replaced,
where a methylene group linked to an imino nitrogen atom of the cycloalkyleneimino group can be replaced by a carbonyl or sulfonyl group or in a 5- to 7-membered monocyclic or fused to a phenyl group cycloalkyleneimino group both methylene groups linked to the imino nitrogen atom by one each Carbonyl group can be replaced
means
or R _{6 is} a C _1-4 alkyl group which is substituted by a carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 alkyl) aminocarbonyl group or is substituted by a 4- to 7-membered cycloalkyleneiminocarbonyl group,
an N- (C _1-3 -alkyl) -C _2-4 -alkanoylamino group which is additionally substituted in the alkyl part by a carboxy or C _1-3 -alkoxycarbonyl group,
a group of the formula

-N (R ₁₂ ) -CO- (CH ₂ ) _p -R ₁₃ (IV)

in the
R _{12 is} a hydrogen atom, a C _1-6 alkyl or C _3-7 cycloalkyl group or a terminal through a phenyl, hetero aryl, trifluoromethyl, hydroxy, C _1-3 alkoxy, aminocarbonyl -, C _1-4 -alkylamino-carbonyl-, di- (C _1-4 -alkyl) - amino-carbonyl-, C _1-3 -alkyl-carbonyl-, C _1-3 -alkyl-sulfonylamino-, N - (C _1-3 alkyl) -C _1-3 alkyl sulfonylamino, C _1-3 alkyl aminosulfonyl or di (C _1-3 alkyl) aminosulfonyl group substituted C _1-3 -Alkyl group and
p represents one of the numbers 0, 1, 2 or 3 and
R _{13 has} the meanings of the abovementioned group R ₇ , or, if p represents one of the numbers 1, 2 or 3, also denotes a hydrogen atom,
a group of the formula

N (R ₁₄ ) - (CH ₂ ) _q - (CO) _r -R ₁₅ (V)

in the
R _{14 is} a hydrogen atom, a C _1-4 alkyl group, a C _1-3 alkylcarbonyl, arylcarbonyl, phenylC _1-3 alkylcarbonyl, heteroarylcarbonyl, heteroarylC _1-3 alkylcarbonyl, C _1-4 -alkylsulfonyl-, arylsulfonyl-, phenyl-C _1-3 -alkylsulfonyl-, heteroarylsulfonyl- or heteroaryl-C _1-3 -alkylsulfonyl groups,
q one of the numbers 1, 2, 3 or 4,
r represents the number 1 or, if q is one of the numbers 2, 3 or 4, also the number 0 and
R _{15 has} the meanings of the aforementioned group R ₇ ,
a group of the formula

-N (R ₁₆ ) -SO ₂ -R ₁₇ (VI)

in the
R _{16 is} a hydrogen atom or a C _1-4 alkyl group optionally substituted by a cyano, trifluoromethyl-carbonyl-amino or N- (C _1-3 -alkyl) -trifluoromethyl-carbonyl-amino group and
R _{17 represents} a C _1-3 alkyl group,
one by a di (C _1-3 alkyl) amino C _1-3 alkyl carbonyl or di (C _1-3 alkyl) amino C _1-3 alkyl sulfonyl group and a di - (C _1-3 alkyl) aminocarbonylC _1-3 alkyl group substituted amino group,
or an N- (C _1-3 alkyl) -C _1-5 alkylsulfonylamino or N- (C _1-3 alkyl) phenylsulfonylamino group in which the alkyl part is additionally substituted by a cyano or carboxy group,
where all the single-bonded or fused-on phenyl groups contained in the radicals mentioned under R _{6 are represented} by fluorine, chlorine, bromine or iodine atoms, by C _1-5 -alkyl, trifluoromethyl, hydroxy, C _1-3 -alkoxy- , Carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-4 alkylamino car bonyl, di (C _1-4 alkyl) amino carbonyl, aminosulfonyl C _1-3 alkyl aminosulfonyl, di (C _1-3 alkyl) aminosulfonyl, C _1-3 alkyl sulfonylamino, nitro or cyano groups may be mono- or disubstituted, where the substituents may be the same or different, or two neighboring hydrogen atoms of the phenyl groups can be replaced by a methylene dioxy group,
and
R _{5 represents} a hydrogen atom or a C _1-3 alkyl group,
where under the expression an aryl group, optionally by a fluorine, chlorine, bromine or iodine atom, by a cyano, trifluoromethyl, nitro, carboxy, aminocarbonyl, C _1-3 alkyl or C _1-3 -Alkoxy group mono- or disubstituted phenyl or naphthyl group and
under the expression a heteroaryl group, a monocyclic 5- or 6-membered heteroaryl group optionally substituted by a C _1-3 alkyl group in the carbon, where
the 6-membered heteroaryl group has one, two or three nitrogen atoms and
the 5-membered heteroaryl group is an imino group optionally substituted by a C _1-3 alkyl or phenylC _1-3 alkyl group, an oxygen or sulfur atom or
an imino group optionally substituted by a C _1-3 alkyl or phenyl-C _1-3 alkyl group or an oxygen or sulfur atom and additionally a nitrogen atom or
contains an imino group optionally substituted by a C _1-3 alkyl or phenylC _1-3 alkyl group and two nitrogen atoms,
and in addition, a phenyl ring can be fused to the abovementioned monocyclic heterocyclic groups via two adjacent carbon atoms and the bond takes place via a nitrogen atom or via a carbon atom of the heterocyclic part or an annexed phenyl ring,
to understand
the hydrogen atoms in the alkyl and alkoxy groups mentioned above or in the alkyl parts contained in the groups of formula I defined above can be partially or completely replaced by fluorine atoms,
the saturated alkyl and alkoxy parts present in the groups defined above, which contain more than 2 carbon atoms, also include their branched isomers, such as the isopropyl, tert-butyl, isobutyl group, unless stated otherwise, and
where in addition the hydrogen atom of an existing carboxy group or a hydrogen atom bonded to a nitrogen atom, for example an amino, alkylamino or imino group or a saturated N-heterocycle such as the piperidinyl group, can each be replaced by a residue which can be split off in vivo.

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

A subgroup of compounds of the general formula I which should be mentioned in particular are those in which
X, R ₁ and R ₃ to R _{5 are} as defined above and
R _{2 is} a linear or branched C _1-6 alkoxycarbonyl group, a C _4-7 cycloalkoxycarbonyl or an aryloxycarbonyl group,
a linear or branched C _1-6 alkoxycarbonyl group which is terminated in the alkyl part by a phenyl, heteroaryl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di ( C _1-3 alkyl) aminocarbonyl group is substituted,
a linear or branched C _2-6 alkoxy carbonyl group which is terminated in the alkyl part by a chlorine atom or a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _{1- 3} -Alkyl) -amino group is substituted means
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

A second subgroup of compounds of the general formula I which should be particularly mentioned are those in which
X, R ₁ and R ₃ to R _{5 are} as defined above and
R _{2 is} an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2-position of the ethyl group by a hydroxy or C _1-3 alkoxy group, or, provided that R _{4 is} not an aminosulfonylphenyl or N- (C _1-5 -alkyl) ) -C _1-3 alkylaminocarbonylphenyl group, also means a di- (C _1-2 alkyl) aminocarbonyl group,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

A third subgroup of compounds of the general formula I which should be mentioned in particular are those in which
X, R ₁ to R ₃ and R _{5 are} as defined above and
R _{4 is} an R ₇ - (C _1-4 alkyl) phenyl group in which
R _{7 is} an amino, C _1-7 alkylamino, di (C _1-7 alkyl) amino, phenylamino, N-phenyl-C _1-3 alkylamino, phenyl-C _{1- 3} -alkylamino-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino- or di- (phenyl-C _1-3 -alkyl) -amino group,
or one through the group of formula

-N (R ₁₂ ) -CO- (CH ₂ ) _p -R ₁₃ (IV),

in which R ₁₂ , p and R _{13 are} as defined above means substituted phenyl group,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

Preferred compounds of general formula I are those in which
R ₁ and R _{3 are} as defined above and
X is an oxygen atom,
R _{2 is} a carboxy group, a linear or branched C _1-6 alkoxy-carbonyl group, a C _5-7 cycloalkoxycarbonyl or a phenoxycarbonyl group,
a linear or branched C _1-3 alkoxycarbonyl group which is terminated in the alkyl part by a phenyl, heteroaryl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di ( C _1-3 alkyl) aminocarbonyl group is substituted,
a linear or branched C _2-3 alkoxy-carbonyl group which is terminated in the alkyl part by a chlorine atom, by a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _{1 -3} -alkyl) -amino group is substituted,
an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group which is optionally substituted in the 2-position of the ethyl group by a hydroxy or C _1-3 alkoxy group or, if R _{4 is} not aminosulfonylphenyl or N- (C _1-5 alkyl) - C Represents _1-3 alkylaminocarbonylphenyl group, also a di (C _1-2 alkyl) aminocarbonyl group,
R _{4 is} a C _3-7 cycloalkyl group,
wherein the methylene group in position 4 of a 6- or 7-membered cycloalkyl group is substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or by an -NH- or -N (C _1-3 alkyl) group can be replaced,
or a phenyl group substituted by the group R ₆ , which is additionally substituted by fluorine, chlorine or bromine atoms, by C _1-3 alkyl, trifluoromethyl, hydroxy, C _1-3 alkoxy, carboxy, C _{1 -3-} alkoxycarbonyl, amino, acetylamino, aminocarbonyl, C _1-3 alkyl aminocarbonyl, di (C _1-3 alkyl) aminocarbonyl, nitro or cyano groups can be mono- or disubstituted, where the substituents can be the same or different and where
R _{6 is} a hydrogen, fluorine, chlorine, bromine or iodine atom,
a cyano, nitro, amino, C _1-5 alkyl, C _3-7 cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl group,
the group of the formula

in which a hydrogen atom bonded to a nitrogen atom can be replaced by a C _1-3 alkyl group,
a C _1-3 alkoxy group, an amino C _2-3 alkoxy, C _1-3 alkylamino C _2-3 alkoxy, di (C _1-3 alkyl) amino C _{2- 3} -alkoxy-, phenyl- C _1-3 -alkylamino-C _2-3 -alkoxy-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -al kylamino-C _2-3 -alkoxy- , Pyrrolidino-C _2-3 alkoxy, pipe ridino-C _2-3 alkoxy or C _1-3 alkyl mercapto group,
a carboxy, C _1-4 alkoxycarbonyl, aminocarbonyl, C _1-3 alkyl amino carbonyl, phenyl C _1-3 alkylamino carbonyl or N- (C _1-3 alkyl) phenyl -C _1-3 alkylamino carbonyl group,
a C _3-7 cycloalkyl carbonyl group,
where the methylene group in position 4 of the 6 or 7-membered cycloalkyl part can be replaced by a -NH or -N (C _1-3 alkyl) group,
a 4- to 7-membered cycloalkyleneimino group in which
a methylene group linked to the imino group can be replaced by a carbonyl or sulfonyl group or
one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group or / and
each the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group by a carboxy-, C _1-3 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocar bonyl-, di- (C _1-3 -alkyl) - aminocarbonyl, phenyl-C _1-3 alkyl amino or N- (C _1-3 alkyl) phenyl-C _1-3 alkylamino group or
can be replaced by an oxygen or sulfur atom, by a sul finyl, sulfonyl, -NH or -N (C _1-3 alkyl) group,
a C _1-4 alkyl group terminally substituted by the group R ₇ , where
R _{7 is} a C _5-7 cycloalkyl group,
wherein the methylene group in position 4 of a 6- or 7- membered cycloalkyl group can be replaced by a -NH or -N (C _1-3 alkyl) group or
in a 5- to 7-membered cycloalkyl group, a - (CH ₂ ) ₂ group can be replaced by a -CO-NH group, a - (CH ₂ ) ₃ group by a -NH-CO-NH- erse 99999 00070 552 001000280000000200012000285919988800040 0002010042696 00004 99880 or a - (CH ₂ ) ₄ group can be replaced by an -NH-CO-NH-CO group, each of which has a hydrogen atom attached to a nitrogen atom replaced by a C _1-3 alkyl group can be replaced
a phenyl or heteroaryl group,
a hydroxy or C _1-3 alkoxy group,
an amino, C _1-6 alkylamino, di (C _1-6 alkyl) amino, phenylamino, N-phenyl-C _1-3 -alkyl-amino-, phenyl-C _1-3 - al kylamino-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino- or di- (phenyl-C _1-3 -alkyl) -amino group,
a ω-hydroxy-C _2-3 -alkyl-amino-, N- (C _1-3 -alkyl) -ω-hy droxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _{2 -3-} alkyl) -amino-, di- (ω- (C _1-3 -alkoxy) -C _2-3 -alkyl) -amino- or N- (dioxolan-2-yl) -C _1-3 - alkyl amino group,
a C _1-3 -alkylcarbonylamino-C _2-3 -alkylamino- or C _1-3 -alkylcarbonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
a C _1-3 -alkylsulfonylamino-, N- (C _1-3 -alkyl) -C _1-3 -alkylsulfonylamino-, C _1-3 -alkylsulfonylamino-C _2-3 -alkylamino- or
C _1-3 alkylsulfonylamino-C _2-3 alkyl-N- (C _1-3 alkyl) amino group,
a hydroxycarbonyl-C _1-3 alkylamino or N- (C _1-3 alkyl) -hydroxycarbonyl-C _1-3 alkylamino group
a guanidino group in which a hydrogen atom can be replaced by a C _1-3 alkyl group,
a group of the formula

-N (R ₈ ) -CO- (CH ₂ ) _n -R ₉ (II),

in the
R _{8 is} a hydrogen atom or a C _1-3 alkyl group,
n one of the numbers 0, 1, 2 or 3 and
R _{9 is} an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, phenylamino, benzylamino or C _1-4 alkoxy group, a 5- to 7-membered cycloalkyleneimino group, where the methylene group in position 4 of the piperidino group through an oxygen or sulfur atom, through an -NH-, -N (C _1-3 alkyl) -, -N (phenyl) -, -N ( _1-3 alkyl carbonyl) - or -N (benzoyl) group can be replaced, or, if n represents one of the numbers 1, 2 or 3, also denote a hydrogen atom,
a group of the formula

N (R ₁₀ ) - (CH ₂ ) _m - (CO) _o -R ₁₁ (III),

in the
R _{10 is} a hydrogen atom, a C _1-3 alkyl group, a C _1-3 alkylcarbonyl or C _1-3 alkylsulfonyl group,
m one of the numbers 1, 2 or 3,
o the number 1 or, if m is one of the numbers 2 or 3, also the number 0 and
R _{11 is} an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, C _1-4 alkoxy or C _1-3 alkoxyC _1-3 alkoxy group or a 5- to 7-membered cyoloalkyleneimino group, the methylene group in position 4 of the piperidino group being represented by an oxygen or sulfur atom, by a -NH-, -N (C _1-3 -alkyl) -, -N (phenyl) -, - N (C _1-3 alkylcarbonyl) - or -N (benzoyl) group can be replaced, mean a C _4-7 cycloalkylamino or C _4-7 cycloalkenylamino group in which position 1 of the ring is not involved in double binding,
a 4- to 7-membered cycloalkyleneimino group in which
the cycloalkylene part can be condensed with a phenyl group or
one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group or / and
the methylene group in position 3 of the pyrrolidino group can be substituted by a hydroxy or C _1-3 alkoxy group,
each the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group by a hydroxy, hydroxy-C _1-3 alkyl, C _1-3 alkoxy, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl -, C _1-3 alkylamino carbonyl, di (C _1-3 alkyl) aminocarbonyl, phenyl-C _1-3 alkylamino or N- (C _1-3 alkyl) phenyl-C _1-3 alkyl amino group substituted or
by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl) -, -N (phenyl) -, -N (phenyl-C _1-3 -alkyl- ) -, -N (C _1-3 -Alkyl-carbonyl) -, -N (C _1-4 -alkoxy-carbonyl -) -, -N (benzoyl) - or -N (phenyl-C _1-3 - alkyl-carbonyl) group can be replaced,
wherein a methylene group linked to an imino nitrogen atom of the cycloalkyleneimino group can be replaced by a carbonyl or sulfonyl group or in a 5- to 6-membered monocyclic or fused to a phenyl group cycloalkyleneimino group both methylene groups linked to the imino nitrogen atom each by a carbonyl group can be replaced
means
or R _{6 is} a C _1-4 alkyl group which is terminated by a carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino carbonyl or di (C _1-3 alkyl) - aminocarbonyl group or substituted by a 4- to 7-membered cycloalkyleneiminocarbonyl group,
a group of the formula

-N (R ₁₂ ) -CO- (CH ₂ ) _p -R ₁₃ (IV),

in the
R _{12 is} a hydrogen atom, a C _1-3 alkyl, C _5-7 cycloalkyl, phenyl C _1-3 alkyl or heteroaryl C _1-3 alkyl group and
p represents one of the numbers 0, 1, 2 or 3 and
R _{13 has} the meanings of the abovementioned group R ₇ or, if p represents one of the numbers 1, 2 or 3, also denotes a hydrogen atom,
a group of the formula

N (R ₁₄ ) - (CH ₂ ) _q - (CO) _r -R ₁₅ (V)

in the
R _{14 is} a hydrogen atom, a C _1-4 alkyl group, a C _1-3 alkyl carbonyl, phenyl carbonyl, phenyl C _1-3 alkyl carbonyl heteroaryl carbonyl, heteroaryl C _1-3 alkyl carbonyl, C _{1 -4-} alkylsulfonyl, phenylsulfonyl, phenyl-C _1-3 -alkylsulfonyl- heteroarylsulfonyl or heteroaryl-C _1-3 -alkyl sulfonyl groups,
q one of the numbers 1, 2, 3 or 4,
r represents the number 1 or, if q is one of the numbers 2, 3 or 4, also the number 0 and
R _{15 has} the meanings of the aforementioned group R ₇ ,
a group of the formula

-N (R ₁₆ ) -SO ₂ -R ₁₇ (VI)

in the
R ₁₆ is a hydrogen atom or a terminally substituted by a cyano, trifluoromethyl-carbonyl-amino or N- (C _1-3 alkyl) -trifluoromethyl-carbonyl-amino group of sub-substituted C _1-4 alkyl group and
R _{17 represents} a C _1-3 alkyl group,
one by a di (C _1-3 alkyl) amino C _1-3 alkyl carbonyl or di (C _1-3 alkyl) amino C _1-3 alkyl sulfonyl group and a di - (C _1-3 alkyl) aminocarbonylC _1-3 alkyl group substituted amino group,
where all the single-bonded or fused-on phenyl groups contained in the radicals mentioned under R ₆ by fluorine, chlorine or bromine atoms, by C _1-3 alkyl, trifluoromethyl, hydroxy, C _1-3 alkoxy, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino carbonyl, aminosulfonyl, C _1-3 alkylaminosulfonyl, nitro or cyano groups may be mono- or disubstituted, the substituents being the same or different may be, or two adjacent hydrogen atoms of the phenyl groups may be replaced by a methylenedioxy group, and
R _{5 represents} a hydrogen atom or a C _1-3 alkyl group,
where, under a heteroaryl group mentioned above, a pyridinyl, pyrazinyl, pyrimidinyl, pyridazyl, pyrrolyl, furyl, thienyl, oxazolyl, thiazolyl, pyrazolyl, optionally substituted in the carbon skeleton by a C _1-3 alkyl group, Imidazolyl or triazolyl group, in which a hydrogen atom bonded to a nitrogen atom can be replaced by a C _1-3 alkyl or phenyl C _1-3 alkyl group and wherein the 5-membered, at least one imino group contain the heteroaryl groups via a carbon - or nitrogen atom are bound to understand
a hydrogen atom bonded to a nitrogen atom in the abovementioned radicals can be replaced by a radical which can be split off in vivo, in particular by an acetyl or tert-butoxycarbonyl group,
the carboxy groups contained in the abovementioned radicals are likewise each substituted by a radical which can be split off in vivo and can be present, for example, in the form of the tert-butoxycarbonyl group,
the hydrogen atoms in the alkyl and alkoxy groups mentioned above or in the alkyl parts contained in the groups of formula I defined above can be replaced in whole or in part by fluorine atoms and
the saturated alkyl and alkoxy parts which contain more than 2 carbon atoms and which are present in the radicals mentioned above may be linear or branched, unless stated otherwise,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

A subgroup of preferred compounds of the general formula I which should be mentioned in particular are those in which
X, R ₁ and R ₃ to R _{5 are} as defined above and
R _{2 is} a linear or branched C _1-6 alkoxycarbonyl group, a C _5-7 cycloalkoxycarbonyl or a phenoxycarbonyl group,
a linear or branched C _1-3 -alkoxy-carbonyl group which is terminated in the alkyl part by a phenyl-carboxy-, C _1-3 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocarbonyl- or di- (C _{1- 3-} alkyl) -aminocarbonyl group is substituted,
a linear or branched C _2-3 alkoxy-carbonyl group which is terminated in the alkyl part by a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _1-3 alkyl ) amino group is substituted means
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

A second, particularly to be mentioned subset of preferred compounds of general formula I are those in which
X, R ₁ and R ₃ to R _{5 are} as defined above and
R _{2 is} an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2-position of the ethyl group by a hydroxy or C _1-3 alkoxy group, or, provided that R _{4 is} not an aminosulfonylphenyl or N- (C _1-5 -alkyl) ) -C _1-3 alkylaminocarbonylphenyl group, also means a di- (C _1-2 alkyl) aminocarbonyl group,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

A third subgroup of preferred compounds of the general formula I which should be mentioned in particular are those in which
X, R ₁ to R ₃ and R _{5 are} as defined above and
R _{4 is} an R ₇ - (nC _1-4 alkyl) phenyl group in which
R _{7 is} an amino, C _1-6 alkylamino, di (C _1-6 alkyl) amino, phenylamino, N-phenyl-C _1-3 alkylamino, phenyl-C _{1- 3} -alkylamino-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino- or di- (phenyl-C _1-3 -alkyl) -amino group,
or one through the group of formula

-N (R ₁₂₎ -CO- (CH ₂ ) _p -R ₁₃ (IV)

in which R ₁₂ , p and R _{13 are} as defined above means substituted phenyl group,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

Particularly preferred compounds of the general formula I are those in which
X is an oxygen atom,
R _{1 is} a hydrogen atom,
R _{2 is} a carboxy group, a linear or branched C _1-4 alkoxycarbonyl group or a phenoxycarbonyl group,
a linear or branched C _1-3 alkoxycarbonyl group which is terminated in the alkyl part by a phenyl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _{1- 3-} alkyl) -aminocarbonyl group is substituted,
a linear or branched C _2-3 alkoxy-carbonyl group which is terminated in the alkyl part by a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _1-3 alkyl ) amino group is substituted,
an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2-position of the ethyl group by a hydroxyl or C _1-3 alkoxy group or, provided that R _{4 is} not an aminosulfonylphenyl or N- (C _1-5 -alkyl) group, C _1-3 alkylaminocarbonylphenyl group, also a di (C _1-2 alkyl) aminocarbonyl group,
R _{3 is} a C _1-4 alkyl group or a phenyl group which can be substituted by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C _1-3 alkyl, hydroxy or C _1-3 alkoxy group,
R _{4 is} a C _5-6 cycloalkyl group,
wherein the methylene group in position 4 of the cyclohexyl group is substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or by an -NH- or -N (C _1-3 Alkyl) group can be replaced,
a phenyl group, a phenyl group disubstituted by C _1-3 alkyl, C _1-3 alkoxy or nitro groups, where the substituents can be identical or different, or
a phenyl group substituted by the group R ₆ , which may additionally be substituted by a fluorine, chlorine or bromine atom or by an amino or nitro group, where R _{6 is} a fluorine, chlorine or bromine atom,
a C _1-3 alkyl, C _1-3 alkoxy, nitro, amino or C _5-6 cycloalkyl group,
a pyrrolyl, pyrazolyl, imidazolyl, triazolyl or tetrazolyl group bonded via a carbon atom, it being possible for the heteroaromatic groups mentioned in the carbon skeleton to be substituted by a C _1-3 alkyl group or a hydrogen atom bonded to a nitrogen atom by a C _{1- 3} -Alkyl- or phenyl-C _1-3 alkyl group can be replaced,
the group of the formula

a carboxy, C _1-4 alkoxycarbonyl, phenylC _1-3 alkyl amino carbonyl or C _5-7 cycloalkyl carbonyl group,
a 5- or 6-membered cycloalkyleneimino group, where
the methylene group in position 4 of the piperidino group can be replaced by an oxygen or sulfur atom, by an -NH or -N (C _1-3 alkyl) group,
an unbranched C _1-3 alkyl group which is terminally substituted by the group R ₇ , where
R _{7 is} a C _5-7 cycloalkyl group,
in a 5- or 6-membered cycloalkyl group a - (CH ₂ ) ₂ group can be replaced by a -CO-NH group, a - (CH ₂ ) ₃ group can be replaced by a -NH-CO-NH- may be or a - (CH ₂ ) ₄ group may be replaced by a -NH-CO-NH-CO group, where in each case a hydrogen atom bonded to a nitrogen atom may be replaced by a C _1-3 alkyl group,
a phenyl or pyridinyl group or a pyrrolyl, pyrazolyl, imidazolyl or triazolyl group bonded via a carbon or nitrogen atom, it being possible for the heteroaromatic groups mentioned in the carbon skeleton to be substituted by a C _1-3 alkyl group or a hydrogen atom bonded to a nitrogen atom can be replaced by a C _1-3 alkyl group,
a hydroxy or C _1-3 alkoxy group,
an amino-, C _1-6 -alkylamino-, di- (C _1-6 -alkyl) -amino-, phenylamino-, N-phenyl-C _1-3 -alkyl-amino-, phenyl-C _{1 -3-} alkylamino or N- (C _1-3 alkyl) phenyl- C _1-3 alkylamino group,
an ω-hydroxy-C _2-3 -alkyl-amino-, N- ( _1-3 -alkyl) -ω-hydroxy-C _2-3 -alkyl-amino-, di- (ω-hy droxy-C _{2 -3-} alkyl) -amino- or di- (ω- (C _1-3 -alk oxy) -C _2-3 -alkyl) -amino group,
a C _1-3 -alkylcarbonylamino-C _2-3 -alkylamino- or C _1-3 -alkylcarbonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
a C _1-3 -alkylsulfonylamino-, N- (C _1-3 -alkyl) -C _1-3 -alkylsulfonylamino-, C _1-3 -alkylsulfonylamino-C _2-3 -alkylamino- or
C _1-3 alkylsulfonylamino-C _2-3 alkyl-N- (C _1-3 alkyl) amino group,
a hydroxycarbonyl-C _1-3 -alkylamino- or N- (C _1-3 -alkyl) -hydroxycarbonyl-C _1-3 -alkyl-amino group,
a guanidino group in which a hydrogen atom can be replaced by a C _1-3 alkyl group,
a group of the formula

-N (R ₈ ) -CO- (CH ₂ ) _n -R ₉ (II),

in the
R _{8 is} a hydrogen atom or a C _1-3 alkyl group,
n one of the numbers 0, 1, 2 or 3 and
R _{9 is} an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or C _1-4 alkoxy group, a 5- or 6-membered cycloalkyleneimino group, the methylene group in Posi tion 4 of the piperidino group can be replaced by an -NH-, -N (C _1-3 -alkyl) - or -N (C _1-3 -alkylcarbonyl) group, or, if n is one of the numbers 1, 2 or 3 also represents a hydrogen atom,
a group of the formula

-N (R ₁₀ ) - (CH ₂ ) _m - (CO) _o -R ₁₁ (III),

in the
R _{10 represents} a hydrogen atom or a C _1-3 alkyl group,
m one of the numbers 1, 2 or 3,
o the number 1 or, if m is one of the numbers 2 or 3, also the number 0 and
R _{11 is} an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, C _1-4 alkoxy or methoxyC _1-3 alkoxy group or a 5- or 6th -linked cycloalkyleneimino group, where the methyl group in position 4 of the piperidino group can be replaced by an -NH-, -N (C _1-3 -alkyl) - or -N (C _1-3 -alkyl-carbonyl) group ,
an azetidino, pyrrolidino, piperidino, 2,6-dimethyl-piperidino, 3,5-dimethyl-piperidino or azepino group, where
the methylene group in position 3 of the pyrrolidino group can be substituted by a hydroxyl group,
the methylene group in position 4 of the piperidino group is substituted by a hydroxy, hydroxyC _1-3 alkyl or C _1-3 alkoxy group or
through an oxygen or sulfur atom, through a sulfinyl, sulfonyl, -NH-, -N (C _1-3 alkyl) -, -N (C _1-3 alkyl carbonyl) -, -N (benzoyl) - or -N (phenyl-C _1-3 -alkylcarbonyl) group can be replaced,
where a methylene group linked to an imino nitrogen atom of the pyrrolidino, piperidino or piperazino group can be replaced by a carbonyl group,
means
or R _{6 is} a straight-chain C _1-3 alkyl group which is terminally substituted by a carboxy or C _1-3 alkoxy carbonyl group,
a group of the formula

-N (R ₁₂ ) -CO- (CH ₂ ) _p -R ₁₃ (IV),

in the
R _{12 is} a hydrogen atom, a C _1-3 alkyl or phenylC _1-3 alkyl group,
p one of the numbers 0, 1 or 2 and
R _{13 is} an amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, benzylamino, N- (C _1-3 alkyl) benzylamino, C _1-3 - Alk oxy-C _1-3 -alkylamino-, N- (C _1-3 -alkyl) -C _1-3 -alkoxy-C _1-3 -alkylamino-, di- (2-methoxy-ethyl) -amino- , Di- (ω-hydroxy-C _2-3 -alkyl) -amino or aminocarbonyl-methyl-N- (methyl) -amino group,
a pyrrolyl, pyrazolyl or imidazolyl group bonded via a nitrogen atom and optionally substituted by a C _1-3 alkyl group,
a pyrrolidino, piperidino, morpholino, thio morpholino or in the 4-position, optionally by a C _1-3 alkyl, phenyl C _1-3 alkyl, C _1-3 alkyl carbonyl or C _1-4 alkoxycarbonyl group substituted piperazino group or, if n represents the number 1 or 2, also represent a hydrogen atom,
a group of the formula

-N (R ₁₄ ) - (CH ₂ ) _q - (CO) _r -R ₁₅ (V)

in the
R _{14 is} a hydrogen atom, a C _1-4 alkyl, C _1-3 alkyl carbonyl, phenylcarbonyl, phenyl C _1-3 alkylcarbonyl, furyl carbonyl, pyridinyl carbonyl, furyl C _{1- 3-} alkylcarbonyl, pyridinyl-C _1-3 -alkylcarbonyl, C _1-4 -alkylsulfonyl, phenylsulfonyl or phenyl-C _1-3 -alkylsulfonyl group,
q one of the numbers 1, 2 or 3,
r represents the number 1 or, if q is one of the numbers 2 or 3, also the number 0 and
R _{15 is} an amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino or N- (C _1-4 alkyl) benzylamino group,
or a group of the formula

-N (R ₁₆ ) -SO ₂ -R ₁₇ (VI),

in the
R ₁₆ is a hydrogen atom or a terminally substituted by a cyano, trifluoromethyl-carbonyl-amino or N- (C _1-3 alkyl) -trifluoromethyl-carbonyl-amino group, substituted C _1-3 alkyl group and
R _{17 represents} a C _1-3 alkyl group,
where all of the monobonded or fused phenyl groups contained in the radicals mentioned under R ₆ can be substituted by a fluorine, chlorine or bromine atom, by a methyl, trifluoromethyl, methoxy, nitro or cyano group and
R _{5 represents} a hydrogen atom,
where a hydrogen atom bonded to a nitrogen atom in the abovementioned radicals can be replaced by an acetyl or tert-butoxycarbonyl group,
the carboxy groups contained in the abovementioned radicals can also be in the form of the tert-butoxycarbonyl precursor group and
the saturated alkyl and alkoxy parts which contain more than 2 carbon atoms and which are present in the radicals mentioned above may be linear or branched, unless stated otherwise,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

A particularly noteworthy subgroup of particularly preferred compounds of the general formula I are those in which
X, R ₁ , R ₃ and R ₅ are defined as mentioned above,
R _{2 is} a linear or branched C _1-4 alkoxycarbonyl group or a phenoxycarbonyl group,
a linear or branched C _1-3 alkoxycarbonyl group which is terminated in the alkyl part by a phenyl carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 - Alkyl) aminocarbonyl group is substituted, or
a linear or branched C _2-3 alkoxy-carbonyl group which is terminated in the alkyl part by a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _1-3 alkyl ) amino group is substituted, and
R _{4 is} an R ₇ - (nC _1-3 alkyl) phenyl group in which
R _{7 is} an amino, C _1-6 alkylamino, di (C _1-4 alkyl) amino, ω-hydroxy-C _2-3 alkylamino, N- (C _1-3 - Alkyl) -ω-hydroxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _2-3 -alkyl) -amino- or di- (ω- (C _1-3 -alkoxy) - C _2-3 alkyl) amino group,
or one through the group of formula

-N (R ₁₂ ) -CO- (CH ₂ ) _p -R ₁₃ (IV),

in which R ₁₂ , p and R _{13 are} as defined above means substituted phenyl group,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

A second, particularly noteworthy subgroup of particularly preferred compounds of the general formula I are those in which
X, R ₁ , R ₃ and R ₅ are defined as mentioned above,
R _{2 is} an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2-position of the ethyl group by a hydroxy or C _1-3 alkoxy group, or, provided that R _{4 is} not an aminosulfonylphenyl or N- (C _1-5 -alkyl) ) -C _1-3 alkylaminocarbonylphenyl group, also a di (C _1-2 alkyl) aminocarbonyl group and
R _{4 is} an R ₇ - (nC _1-3 alkyl) phenyl group in which
R _{7 is} an amino, C _1-6 alkylamino, di (C _1-4 alkyl) amino, ω-hydroxy-C _2-3 alkylamino, N- (C _1-3 - Alkyl) -ω-hydroxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _2-3 -alkyl) -amino- or di- (ω- (C _1-3 -alkoxy) - C _2-3 alkyl) amino group,
or one through the group of formula

-N (R ₁₂ ) -CO- (CH ₂ ) _p -R ₁₃ (IV),

in which R ₁₂ , p and R _{13 are} as defined above means substituted phenyl group,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

Very particularly preferred compounds of the general formula I are those in which
X is an oxygen atom,
R ₁ and R ₅ each represent a hydrogen atom,
R _{2 is} a methoxycarbonyl, ethoxycarbonyl or aminocarbonyl group,
R _{3 is} a phenyl group and
R _{4 is} a phenyl group monosubstituted by the group R ₆ , where at
R _{6 is} an N-methylimidazol-2-yl group,
an unbranched C _1-3 alkyl group which is terminally substituted by a C _1-4 alkylamino, di (C _1-4 alkyl) amino, piperidino or 2,6-dimethylpiperidino group,
a group of the formula

-N (R ₁₂ ) -CO- (CH ₂ ) _p -R ₁₃ (IV),

in the
R _{12 is} a C _1-3 alkyl group,
p one of the numbers 1 or 2 and
R _{13 is} a di (C _1-3 alkyl) amino group,
or a group of the formula

-N (R ₁₄ ) - (CH ₂ ) _q - (CO) _r -R ₁₅ (V)

in the
R _{14 is} a C _1-3 alkylcarbonyl or C _1-3 alkylsulfonyl group,
q one of the numbers 1, 2 or 3,
r the number 1 or, if q is one of the numbers 2 or 3, the number 0 and
R _{15 represents} a di (C _1-3 alkyl) amino group,
represent
where the saturated alkyl parts which contain more than 2 carbon atoms contained in the abovementioned radicals can be linear or branched, unless stated otherwise,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

A subgroup of very particularly preferred compounds of the general formula I which should be mentioned in particular are those in which
X, R ₁ , R ₃ and R ₅ are defined as mentioned above,
R _{2 is} a methoxycarbonyl or ethoxycarbonyl group and
R _{4 is} a di (C _1-3 alkyl) amino C _1-3 alkylphenyl group or
one by the group of formula

-N (R ₁₂ ) -CO- (CH ₂ ) _p -R ₁₃ (IV)

in which R ₁₂ , p and R _{13 are} as defined above means substituted phenyl group,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts.

The following are particularly preferred compounds:

• a) 3-Z- [1- (4- (Piperidin-1-ylmethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone,
• b) 3-Z - [(1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylme ethylene] -6-carbamoyl-2-indolinone,
• c) 3-Z- [1- (4- (Piperidin-1-ylmethyl) anilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone,
• d) 3-Z- [1- (4- (Dimethylaminomethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone,
• e) 3-Z- [1- (4 - ((2,6-dimethylpiperidin-1-yl) methyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• f) 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-acetylamino) -ani lino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• g) 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) -ani lino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• h) 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonyl-ami no) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• i) 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone,
• j) 3-Z- [1- (4- (N-acetyl-N-dimethylaminocarbonylmethylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,
• k) 3-Z- [1- (4-ethylaminomethyl-anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone,  
• l) 3-Z- [1- (4- (1-methylimidazol-2-yl) anilino) -1-phenyl methylene] -6-methoxycarbonyl-2-indolinone,
• m) 3-Z- [1- (4- (N-dimethylaminomethylcarbonyl-N-methylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,
• n) 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonyl-ami no) -anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,
• o) 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-methylsulfonyl amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indoli non,
• p) 3-Z- [1- (4- (N-Dimethylaminocarbonylmethyl-N-methylsulfonyl amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indoli non,
• q) 3-Z- [1- (4- (N - ((2-Dimethylaminoethyl) carbonyl) -N-methyl amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indo linon,
• r) 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-acetylamino) -ani lino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone and
• s) 3-Z- [1- (4-methylaminomethyl-anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone,

their tautomers, their mixtures and their salts.

A further subgroup of compounds of the general formula I are those in which
X is an oxygen or sulfur atom,
R _{1 is} a hydrogen atom or a prodrug residue such as a C _1-4 alkoxycarbonyl or C _2-4 alkanoyl group,
R _{2 is} a carboxy group, a linear or branched C _1-6 alkoxycarbonyl group, a C _5-7 cycloalkoxycarbonyl or phenyl-C _1-3 alkoxycarbonyl group, an aminocarbonyl or C _1-2 alkylaminocarbonyl group or, if so R ₄ does not represent an aminosulfonylphenyl or N- (C _1-5 -alkyl) -C _1-3 -alkylaminocarbonyl-phenyl group, also a di- (C _1-2 -alkyl) -aminocarbonyl group,
R _{3 is} a hydrogen atom, a C _1-6 alkyl, C _1-7 cycloalkyl, trifluoromethyl or heteroaryl group,
a phenyl or naphthyl group, one by a fluorine, chlorine, bromine or iodine atom, by a trifluoromethyl, C _1-3 alkyl or C _1-3 alkoxy group mono- or disubstituted phenyl or naphthyl group, in which In the case of disubstitution, the substituents can be the same or different and the above-mentioned unsubstituted as well as the mono- and disubstituted phenyl and naphthyl groups additionally
by a hydroxy, hydroxyC _1-3 alkyl or C _1-3 alkoxyC _1-3 alkyl group,
by a cyano, carboxy, carboxyC _1-3 alkyl, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino carbonyl or di (C _1-3 alkyl) aminocarbonyl group ,
through a nitro group,
by an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or amino C _1-3 alkyl group,
by a C _1-3 alkylcarbonylamino, N- (C _1-3 alkyl) -C _1-3 alkyl kylcarbonylamino, C _1-3 alkylcarbonylamino C _1-3 alkyl, N- (C _{1 -3-} alkyl) -C _1-3 -alkylcarbonylamino-C _1-3 -alkyl-, C _1-3 -alkyl sulfonylamino-, C _1-3 -alkylsulfonylamino-C _1-3 -alkyl-, N- (C _{1 -3-} alkyl) -C _1-3 -alkylsulfonylamino-C _1-3 -alkyl- or aryl-C _1-3 -alkylsulfonylamino group,
by a Cycloalkylamino-, Cycloalkylenimino-, Cycloalkyleniminocarbonyl-, Cycloalkylenimino-C _1-3 -alkyl-, Cycloalkyleniminocarbonyl-C _1-3 -alkyl- or Cycloalkylen iminosulfonyl-C _1-3 -alkyl group each with 4 to 7 ring, whereby in each case the methylene group in position 4 in a 6- or 7-membered cycloalkyleneimino group can be replaced by an oxygen or sulfur atom, by a sul finyl, sulfonyl, -NH or -N (C _1-3 -alkyl) group ,
or can be substituted by a hetexoaryl or heteroarylC _1-3 alkyl group,
R _{4 is} a C _3-7 cycloalkyl group,
wherein the methylene group in position 4 of a 6- or 7- membered cycloalkyl group is substituted by an amino, C _1-3 -alkylamino or di- (C _1-3 -alkyl) -amino group or by an -NH- or -N (C _1-3 alkyl) group can be replaced,
or a phenyl group substituted by the group R ₆ , which is additionally substituted by a fluorine, chlorine, bromine or iodine atom, by a C _1-5 alkyl, trifluoromethyl, C _1-3 alkoxy, carboxy, C _1-3 alkoxycarbonyl, aminosulfonyl, nitro or cyano group may be substituted, wherein
R _{6 is} a hydrogen, fluorine, chlorine, bromine or iodine atom,
a cyano, nitro, C _1-5 alkyl, C _3-7 cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl group,
a C _1-3 alkoxy group optionally substituted by 1 to 3 fluorine atoms, a C _1-3 alkoxy-C _1-3 alkoxy, phenyl alkoxy, amino-C _2-3 alkoxy, C _1-3 - Alkylamino-C _2-3 -alkoxy-, di- (C _1-3 -alkyl) -amino-C _2-3 -alkoxy-, phenyl-C _1-3 -alkylamino- C _2-3 -alkoxy-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino-C _2-3 -alkoxy-, C _5-7 -cycloalkylenimino-C _2-3 -alkoxy- or C _1-3 -alkylmercapto group,
a carboxy-, C _1-4 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylamino-carbonyl-, N- (C _1-5 -alkyl) -C _1-3 -alkylaminocarbonyl-, phenyl-C _{1 -3-} alkylamino-carbonyl-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -al kylamino-carbonyl-, piperazinocarbonyl or N- (C _1-3 -alkyl) -pi perazinocarbonyl group,
a C _1-3 alkylaminocarbonyl or N- (C _1-5 alkyl) -C _1-3 alkyl alkaminocarbonyl group in which an alkyl part is replaced by a carboxy or C _1-3 alkoxycarbonyl group or in 2- or 3- Position is substituted by a di- (C _1-3 alkyl) amino, piperazino, N- (C _1-3 alkyl) piperazino or a 4- to 7-membered cycloalkyleneimino group,
a 4- to 7-membered cycloalkyleneimino group in which
a methylene group linked to the imino group can be replaced by a carbonyl or sulfonyl group or
the cycloalkylene part can be condensed with a phenyl ring or
one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group or / and
each the methylene group in position 4 of a 6- or 7- membered cycloalkyleneimino group by a carboxy-, C _1-3 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocar bonyl-, di- (C _1-3 -alkyl) - aminocarbonyl, phenyl-C _1-3 alkyl amino or N- (C _1-3 alkyl) phenyl-C _1-3 alkylamino group or
through an oxygen or sulfur atom, through a sul finyl, sulfonyl, -NH,, -N (C _1-3 alkyl) -, -N (phenyl) -, -N (C _1-3 alkyl carbonyl ) - or -N (benzoyl) group can be replaced,
a C _1-4 alkyl group, the
by a hydroxy or C _1-3 alkoxy group,
by an amino-, C _1-7 -alkylamino-, di- (C _1-7 -alkyl) -amino-, di-N- (C _1-3 -alkyl) -amino-C _2-3 -alkylamino-, Tri-N, N, N '- (C _1-3 -alkyl) -amino-C _2-3 -alkylamino-, phenylamino-, N-phenyl-C _1-3 -alcyl-amino-, phenyl-C _1-3 alkylamino, N- (C _1-3 alkyl) phenylC _1-3 alkylamino or di (phenylC _1-3 alkyl) amino group,
by a C _1-3 -alkylcarbonylamino-, N- (C _1-3 -alkyl) -C _1-3 -alkylcarbonylamino-, C _1-3 -alkoxycarbonyl-C _1-3 -alkylamino- or N- (C _{1 -3-} alkyl) -C _1-3 -alkoxycarbonyl-C _1-3 -alkylamino group,
by a C _4-7 cycloalkylamino, C _4-7 cycloalkyl-C _1-3 alkyl amino or C _4-7 cycloalkenylamino group, in which the position 1 of the ring is not involved in the double bond, and wherein the Groups mentioned above each additional Lich on the amine nitrogen atom by a C _1-3 alkyl group, in which the hydrogen atoms are partially or completely replaced by fluorine atoms, by a C _5-7 cycloalkyl, C _2-4 alkenyl or C _1-4 alkyl group can be substituted,
by a 4- to 7-membered cycloalkyleneimino group in which
a methylene group linked to the imino group can be replaced by a carbonyl or sulfonyl group or
the cycloalkylene part with a phenyl group or with an oxazolo or imidazolo optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, C _1-3 alkyl, C _1-3 alkoxy or amino group -, Thiazolo, Pyridino, Pyrazino or Pyrimidino group can be condensed or
one or two hydrogen atoms can each be replaced by a C _1-3 alkyl, C _5-7 cycloalkyl or phenyl group or / and
each the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group by a hydroxy, carboxy, C _1-4 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl, di (C _1-3 - alkyl) -aminocarbonyl-, phenyl-C _1-3 -alkylamino- or N- (C _1-3 -alkyl) -phenyl-C _1-3 -al kylamino group substituted or
through an oxygen or sulfur atom, through a sulfinyl, sulfonyl, -NH-, -N (C _1-3 alkyl) -, -N (phenyl) -, -N (C _1-3 alkyl carbonyl) - or -N (benzoyl) group can be replaced,
by a carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 alkyl) aminocarbonyl group or
is substituted by a 4- to 7-membered cycloalkyleneiminocarbonyl group,
an amino, pyrrolidino, piperidino, morpholino, benzoylamino or N- (C _1-3 -alkyl) -benzoylamino group,
an N- (C _1-3 -alkyl) -C _2-4 -alkanoylamino group which is additionally substituted in the alkyl part by a carboxy or C _1-3 -alkoxycarbonyl group,
a group of the formula

-N (R ₈ ) -CO- (CH ₂ ) _n -R ₉ (II),

in the
R _{8 is} a hydrogen atom or a C _1-3 alkyl group,
n one of the numbers 0, 1, 2 or 3 and
R _{9 is} an amino, C _1-4 alkylamino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino, N- (C _1-4 alkyl) benzyl amino or Di- (C _1-4 -alkyl) -amino group, a 4- to 7-membered cycloalkyleneimino group, the methyl group in position 4 of a 6- or 7-membered cycloalkyleneimino group being represented by an oxygen or sulfur atom, by a sulfinyl , Sulfonyl, -NH-, -N (C _1-3 alkyl) -, -N (phenyl) -, -N (C _1-3 alkyl carbonyl) - or -N (benzoyl) group can be replaced, or, if n represents one of the numbers 1, 2 or 3, also mean a hydrogen atom,
a group of the formula

-N (R ₁₀ ) - (CH ₂ ) _m - (CO) _o -R ₁₁ (III),

in the
R _{10 is} a hydrogen atom, a C _1-3 alkyl group, a C _1-3 alkyl carbonyl, arylcarbonyl, phenyl C _1-3 alkylcarbonyl, C _1-3 alkylsulfonyl, arylsulfonyl or phenyl-C _1-3 -al kylsulfonyl group,
m one of the numbers 1, 2, 3 or 4,
o one of the numbers 0 or 1 and
R _{11 is} an amino, C _1-4 alkylamino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino, N- (C _1-4 alkyl) benzyl amino or Di- (C _1-4 alkyl) amino group, a 4- to 7-membered cycloalkyleneimino group, where the cycloalkylene part can be fused with a phenyl ring or each because the methylene group in position 4 of a 6- or 7- membered cycloalkyleneimino group by an oxygen - or sulfur atom, through a sulfinyl, sulfonyl, -NH, -N (C _1-3 alkyl) -, -N (phenyl) -, -N (C _1-3 alkyl carbonyl) - or - N (benzoyl) group can be replaced, a C _1-3 alkoxy group or a di- (C _1-4 alkyl) amino-C _1- optionally substituted in the 1-position by a C _1-3 alkyl group ₃ - alkylamino group,
or an N- (C _1-3 alkyl) -C _1-5 alkylsulfonylamino or N- (C _1-3 alkyl) phenylsulfonylamino group in which the alkyl part is additionally substituted by a cyano or carboxy group,
where all the single-bonded or fused-on phenyl groups contained in the radicals mentioned under R _{6 are represented} by fluorine, chlorine, bromine or iodine atoms, by C _1-5 -alkyl, trifluoromethyl, C _1-3 -alkoxy-, carboxy- , C _1-3 alkoxycarbonyl, aminosulfonyl, nitro or cyano groups can be mono- or disubstituted, where the substituents can be the same or different, or two adjacent hydrogen atoms of the phenyl groups can be replaced by a methylenedioxy group,
and
R _{5 represents} a hydrogen atom or a C _1-3 alkyl group,
where under the expression an aryl group, a phenyl or naphthyl group which is mono- or di-substituted by a fluorine, chlorine, bromine or iodine atom, by a trifluoromethyl, C _1-3 alkyl or C _1-3 alkoxy group and
a heteroaryl group means a monocyclic 5- or 6-membered heteroaryl group which is optionally substituted by a C _1-3 alkyl group, the 6-membered heteroaryl group having one, two or three nitrogen atoms and the 5-membered heteroaryl group one optionally having a C _{1 -3-} alkyl group-substituted imino group, an oxygen or sulfur atom or an imino group optionally substituted by a C _1-3 alkyl group and an oxygen or sulfur atom or one or two nitrogen atoms, and also to the above-mentioned monocyclic heterocyclic groups A phenyl ring can be fused on via two adjacent carbon atoms.
the saturated alkyl and alkoxy parts present in the groups defined above, which contain more than 2 carbon atoms, also include their branched isomers, such as the isopropyl, tert-butyl, isobutyl group, unless stated otherwise, and
an existing carboxy, amino or imino group can additionally be substituted by a residue which can be split off in vivo,
their isomers and their salts.

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

• a) implementation of a compound of the general formula
  in the
  X and R ₃ are defined as mentioned at the beginning,
  R ₂ 'has the meanings mentioned above for R ₂ ,
  R _{18 is} a hydrogen atom or a protective group for the nitrogen atom of the lactam group, where one of the radicals R ₂ 'and R _{18 can} also be a bond, optionally formed via a spacer, to a solid phase and the other of the radicals R ₂ ' and R ₇ is has the meanings mentioned above, and Z _{1 is} a halogen atom, a hydroxyl, alkoxy or aryl-alk oxy group, for. B. a chlorine or bromine atom, a methoxy, ethoxy or benzyloxy group,
  with an amine of the general formula
  in the
  R ₄ and R ₅ are defined as mentioned in the introduction, and if necessary subsequent cleavage of a protective group used for the nitrogen atom of the lactam group or from a solid phase.
  A protective group for the nitrogen atom of the lactam group is, for example, an acetyl, benzoyl, ethoxycarbonyl, tert-butyloxycarbonyl or benzyloxycarbonyl group and
  as a solid phase, a resin such as a 4- (2 ', 4'-dimethoxyphenylamino methyl) phenoxy resin, the binding advantageously taking place via the amino group, or a p-benzyloxybenzyl alcohol resin, the binding advantageously via an intermediate member such as 2.5 -Dimethoxy-4-hydroxy-benzyl derivative is considered.
  The reaction is advantageously carried out in a solvent such as dimethylformamide, toluene, acetonitrile, tetrahydrofuran, dimethyl sulfoxide, methylene chloride or mixtures thereof, if appropriate in the presence of an inert base such as triethylamine, N-ethyl-diisopropylamine or sodium hydrogen carbonate at temperatures between 20 and 175 ° C. a protective group used can be split off simultaneously as a result of transamidation.
  If Z ₁ in a compound of the general formula VII denotes a halogen atom, the reaction is preferably carried out in the presence of an inert base at temperatures between 20 and 120 ° C.
  If Z ₁ in a compound of the general formula VII denotes a hydroxyl, alkoxy or arylalkoxy group, the reaction is preferably carried out at temperatures between 20 and 200 ° C.
  Any subsequent cleavage of a protective group used is advantageously carried out either hydrolytically in an aqueous or alcoholic solvent, for. B. in methanol / water, ethanol / water, isopropanol / water, tetrahydrofuran / water, dioxane / water, dimethylformamide / - water, methanol or ethanol in the presence of an alkali base such as lithium hydroxide, sodium hydroxide or potassium hydroxide at temperatures between 0 and 100 ° C. , preferably at temperatures between 10 and 50 ° C,
  or advantageously by Umamidierung with an organic base's such as ammonia, butylamine, dimethylamine or Pipe ridin in a solvent such as methanol, ethanol, dimethylformamide and mixtures thereof or in an excess of an amine used at temperatures between 0 and 100 ° C, preferably before at temperatures between 10 and 50 ° C.
  The cleavage of a solid phase used takes place before preferably using 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 R _2, with the exception of the carboxy group, is defined as mentioned at the beginning:
  Implementation of a compound of the general formula
  in the
  R ₁ and R ₃ to R ₅ are defined as mentioned at the outset, or their reactive derivatives with a compound of the general formula
  HR ₁₉ (X),
  in the
  R _{19 is} a C _1-6 alkanol, a C _4-7 cycloalkanol or an aromatic alcohol,
  a C _1-6 alkanol, which is terminated in the alkyl part by a phenyl, heteroaryl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino carbonyl or di (C _1-3 alkyl) aminocarbonyl group is substituted,
  a C _2-6 alkanol which is terminal in the alkyl part by a chlorine atom or a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group is substituted,
  is an amino or methylamino group, an ethylamino group which is optionally substituted by a hydroxy or C _1-3 alkoxy group in the 2-position of the ethyl group or a di (C _1-2 -alkyl) amino group.
  The esterification or amidation is preferably carried out in a solvent such as methylene chloride, diethyl ether, tetrahydrofuran, toluene, dioxane, acetonitrile, dimethyl sulfoxide or dimethylformamide, optionally in the presence of an inorganic or a tertiary organic base, preferably at temperatures between 20 ° C. and the boiling point of the used solvent performed. Here, the reaction with an appropriate acid is preferably in the presence of a dehydrating agent, for. B. in the presence of chloroformic acid isobutyl ester, orthocarbonic acid tetraethyl ester, ortho acetic acid trimethyl ester, 2,2-dimethoxypropane, tetramethoxy silane, thionyl chloride, trimethylchlorosilane, phosphorus trichloride, phosphorus pentoxide, N, N'-dicyclohexylcarbodiimidiimide, cyclin N, N'-dicyclohexyl carbodiimide / 1-hydroxy-benzotriazole, 2- (1H-benzotriazol-1-yl) - 1,1,3,3-tetramethyluronium tetrafluoroborate, 2- (1H-benzotria zol-1-yl) -1,1,3,3-tetramethyluronium tetrafluoroborate / 1-hy droxy-benzotriazole, N, N'-carbonyldiimidazole or triphenyl phosphine / carbon tetrachloride, and optionally with the addition of a base such as pyridine, 4-dimethylaminopyridine, N-methyl morpholine or triethylamine expediently at temperatures between 0 and 150 ° C, preferably at temperatures between 0 and 100 ° C, and the acylation with a corresponding reactive compound such as its anhydride, ester, imidazolide or halide, optionally in the presence of a tertiary n organic base such as triethylamine, N-ethyl-diisopropylamine or N-methyl-morpholine at temperatures between 0 and 150 ° C, preferably at temperatures between 50 and 100 ° C.
• c) For the preparation of a compound of general formula I in which R _{4 represents} a C _1-4 alkyl group substituted by the group R ₇ , where
  R _{7 is} an amino, C _1-7 alkylamino, di (C _1-7 alkyl) amino, phenylamino, N-phenyl-C _1-3 alkylamino, phenyl-C _{1- 3} -alkylamino-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino- or di- (phenyl-C _1-3 -alkyl) -amino group,
  a ω-hydroxy-C _2-3 -alkyl-amino-, N- (C _1-3 -alkyl) -ω-hy droxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _{2 -3-} alkyl) -amino-, di- (ω- (C _1-3 -alkoxy) -C _2-3 -alkyl) -amino- or N- (dioxolan-2-yl) -C _1-3 - alkyl amino group,
  a C _1-3 -alkylcarbonylamino-C _2-3 -alkylamino- or C _1-3 -alkylcarbonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
  a C _1-3 -alkylsulfonylamino-, N- (C _1-3 -alkyl) -C _1-3 -alkylsulfonylamino-, C _1-3 -alkylsulfonylamino-C _2-3 -alkylamino- or
  C _1-3 alkylsulfonylamino-C _2-3 alkyl-N- (C _1-3 alkyl) amino group,
  a group of the formula
  -N (R ₁₀ ) - (CH ₂ ) _m - (CO) _o -R ₁₁ (III),
  in the
  R _{10 is} a hydrogen atom, a C _1-3 alkyl group, a C _1-3 alkylcarbonyl, arylcarbonyl, phenylC _1-3 alkylcarbonyl, C _1-3 alkylsulfonyl, arylsulfonyl or phenyl group C _1-3 alkylsulfonyl group,
  m one of the numbers 1, 2, 3 or 4,
  o the number 1 and
  R _{11 is} an amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino, N- (C _1-4 -alkyl) -benzylamino-, C _1-4 -alkoxy or C _1-3 -alkoxy-C _1-3 -alkoxy group, optionally in the 1-position substituted by a C _1-3 -alkyl group Di (C _1-4 alkyl) aminoC _1-3 alkylamino group or a 4- to 7-membered cycloalkyleneimino group, where the cycloalkylene part can be fused with a phenyl ring or the methylene group in position 4 of a 6- or 7th -linked cycloalkyleneimino group by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 alkyl) -, -N (phenyl) -, -N (C _1-3 alkyl) -carbonyl) - or -N (benzoyl) - group can be replaced, mean
  a C _4-7 cycloalkylamino, C _4-7 cycloalkyl-C _1-3 alkylamino or C _4-7 cycloalkenylamino group in which the 1 position of the ring is not involved in the double bond and where in the aforementioned Groups in each case may additionally be substituted on the amine nitrogen atom by a C _5-7 cycloalkyl, C _2-4 alkenyl or C _1-4 alkyl group,
  or a 4- to 7-membered cycloalkyleneimino group in which
  the cycloalkylene part with a phenyl group or with an oxazolo, imida optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, C _1-3 alkyl, C _1-3 alkoxy or amino group zolo, thiazolo, pyridino, pyrazino or pyrimidino group can be condensed or / and
  one or two hydrogen atoms can each be replaced by a C _1-3 alkyl, C _5-7 cycloalkyl or phenyl group or / and
  the methylene group in position 3 of a 5-membered cycloalkyleneimino group may be substituted by a hydroxy, hydroxy c _1-3 alkyl, C _1-3 alkoxy or C _1-3 alkoxy-C _1-3 alkyl group can,
  each the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group by a hydroxy, hydroxyC _1-3 alkyl, C _1-3 alkoxy, C _1-3 alkoxyC _1-3 -alkyl-, C _1-4 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocarbonyl-, di- (C _1-3 -alkyl) -aminocarbonyl-, phenyl-C _1-3 -alkylamino- or N- ( C _1-3 alkyl) phenyl-C _1-3 alkylamino group substituted or
  by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 alkyl -) -, -N (phenyl) -, -N (phenyl-C _1-3 alkyl) -) -, -N (C _1-3 -Alkyl-carbonyl -) -, -N (C _1-4 -alkoxy-carbonyl -) -, -N (Ben zoyl -) - or -N (phenyl-C _1-3 alkylcarbonyl -) - group can be replaced,
  where a methylene group linked to an imino nitrogen atom of the cycloalkyleneimino group can be replaced by a carbonyl or sulfonyl group or in a 5- to 7-membered monocyclic or fused to a phenyl group cycloalkylene lenimino group, both methylene groups linked to the imino nitrogen atom, each by a car bonyl group can be replaced
  means:
  Implementation of a compound of the general formula
  in the
  R ₃ , R ₅ and X are defined as mentioned at the beginning,
  R ₂ 'has the meanings mentioned above for R ₂ ,
  R _{18 is} a hydrogen atom or a protective group for the nitrogen atom of the lactam group, it being possible for one of the radicals R ₂ 'and R _{18 to} also form a bond to a solid phase which may have been formed via a spacer and the other of the radicals R ₂ ' and R _{18 to be} the above has the meanings mentioned, A is a C _1-4 alkyl group and 22 is a leaving group, for example an alkyl or arylsulfonyloxy group such as methylsulfonyloxy, ethylsulfonyloxy, p-toluenesulfonyloxy or trifluoromethanesulfonyloxy group, with an amine of the general formula
  HR ₇ , (XII),
  in the
  R ₇ , which has the meanings given above for R ₇ , and if necessary subsequent cleavage of a protective group used for the nitrogen atom of the lactam group or from a solid phase.

The reaction is advantageously carried out in a solvent such as methylene chloride, tetrahydrofuran, 1,4-dioxane, toluene, Acetonitrile, dimethyl sulfoxide, dimethylformamide, dimethyl acetamide, N-methylpyrrolidone or mixtures thereof if necessary with the addition of water as cosolvent and / or under Addition of an inert auxiliary base, for example sodium hydro gene carbonate, pyridine, 2,4,6-trimethylpyridine, quinoline, tri ethylamine, N-ethyldiisopropylamine, N-ethyl-dicyclohexylamine, 1,4-diazabicyclo [2,2,2] octane or 1,8-diazabicyclo [5,4,0] - undec-7-en, at temperatures between -50 ° C and + 100 ° C, preferably between -10 ° C and + 50 ° C, where a protective group used as a result of transamidation at the same time can be split off.

The necessary splitting off of a used one Protecting group for the nitrogen atom of the lactam group or of a solid phase takes place as above under method (a) wrote.  

If, according to the invention, a compound of the general formula I is obtained which contains an alkoxycarbonyl group, this can be converted into a corresponding carboxy compound by means of hydrolysis, or
a compound of the general formula I which contains an amino or alkylamino group, this can be converted into a corresponding alkylamino or dialkyl amino compound by means of reductive alkylation, or
a compound of general formula I which contains an amino or alkylamino group, this can be converted into a corresponding acyl or sulfonyl compound by means of acylation or sulfonation, or
a compound of general formula I which contains a carboxy group, this can be converted into an appropriate ester or aminocarbonyl compound by esterification or amidation, or
a compound of the general formula I which contains a cycloalkyleneimino group in which a methylene group is replaced by a sulfur atom, this can be converted into a corresponding sulfinyl or sulfonyl compound by means of oxidation, or
a compound of the general formula I which contains a nitro group, this can be converted into a corresponding amino compound by reduction, or
a compound of the general formula I in which R _{4 represents} a phenyl group substituted by an amino, alkylamino, aminoalkyl or N-alkylamino group, this can then send by reaction with a corresponding cyanate, isocyanate or carbamoyl halide in a corresponding urea compound of the general formula I are converted or
a compound of the general formula I in which R _{4 represents} a phenyl group substituted by an amino, alkylamino, aminoalkyl or N-alkylamino group, this can then be carried out by reaction with a corresponding compound transferring the amidino group or by reaction be converted into a corresponding guanidino compound of the general formula I with an appropriate nitrile.

The subsequent hydrolysis is preferably carried out in an aq Rigen solvent, for. B. in water, methanol / water, ethanol / Water, isopropanol / water, tetrahydrofuran / water or Dioxane / water, in the presence of an acid such as trifluoroacetic acid acid, hydrochloric acid or sulfuric acid or in the presence of a Alkali base such as lithium hydroxide, sodium hydroxide or potassium hydroxide at temperatures between 0 and 100 ° C, preferably at temperatures between 10 and 50 ° C.

The subsequent reductive alkylation is preferably carried out in a suitable solvent such as methanol, methanol / water, Methanol / water / ammonia, ethanol, ether, tetrahydrofuran, di oxane or dimethylformamide, optionally with the addition of a Acid such as hydrochloric acid in the presence of catalytically excited Hydrogen, e.g. B. of hydrogen in the presence of Raney Nickel, platinum or palladium / carbon, or in the presence of a Metal hydrides such as sodium borohydride, lithium borohydride, sodium cyanoborohydride or lithium aluminum hydride at temperatures between 0 and 100 ° C, preferably at temperatures between 20 and 80 ° C carried out.

The subsequent acylation or sulfonylation is used moderately with the corresponding free acid or one appropriate reactive compound such as its anhydride, Ester, imidazolide or halide preferably in one Solvents such as methylene chloride, diethyl ether, tetrahydrofu ran, toluene, dioxane, acetonitrile, dimethyl sulfoxide or dime thylformamide optionally in the presence of an inorganic  or a tertiary organic base at temperatures between between -20 and 200 ° C, preferably at temperatures between 20 ° C and the boiling point of the solvent used, carried out. The reaction with the free acid can counter also in the presence of an acid activating agent or a dehydrating agent, e.g. B. in the presence of Isobutyl chloroformate, tetraethyl orthocarbonate esters, trimethyl orthoacetate, 2,2-dimethoxypropane, Tetramethoxysilane, thionyl chloride, trimethylchlorosilane, Phosphorus trichloride, phosphorus pentoxide, N, N'-dicyclohexyl carbodiimide, N, N'-dicyclohexylcarbodiimide / N-hydroxysuccinimide, N, N'-dicyclohexylcarbodiimide / 1-hydroxy-benzotriazole, 2- (1H-Ben zotriazol-1-yl) -1,1,3,3-tetramethyluronium tetrafluoroborate, 2- (1H-Benzotriazol-1-yl) -1,1,3,3-tetramethyluronium tetra fluoroborate / 1-hydroxy-benzotriazole, N, N'-carbonyldiimidazole or Triphenylphosphine / carbon tetrachloride, and optionally with the addition of a base such as pyridine, 4-dimethylamino-pyridine, N-methyl-morpholine or triethylamine expediently Temperatures between 0 and 150 ° C, preferably at tempera between 0 and 100 ° C. Implementation with a corresponding reactive connection can be given if in the presence of a tertiary organic base such as tri ethylamine, N-ethyl-diisopropylamine, N-methyl-morpholine or Pyridine or when using an anhydride in the presence of the corresponding acid at temperatures between 0 and 150 ° C, preferably at temperatures between 50 and 100 ° C.

The subsequent esterification or amidation is convenient partially by implementing a reactive appropriate Carboxylic acid derivatives with an appropriate alcohol or Amine performed as described above.

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

To prepare a corresponding sulfinyl compound general formula I, the oxidation is conveniently with one equivalent of the oxidizing agent used leads, e.g. B. with hydrogen peroxide in glacial acetic acid, trifluoroacetic acid acid or formic acid at 0 to 20 ° C or in acetone at 0 up to 60 ° C, with a peracid such as performic acid in glacial acetic acid or trifluoroacetic acid at 0 to 50 ° C or with m-chloroperbene zoic acid in methylene chloride, chloroform or dioxane at -20 to 80 ° C, with sodium metaperiodate in aqueous methanol or Ethanol at -15 to 25 ° C, with bromine in glacial acetic acid or aqueous Acetic acid optionally in the presence of a weak base like sodium acetate, with N-bromosuccinimide in ethanol, with tert.- Butyl hypochlorite in methanol at -80 to -30 ° C, with iodine zodichloride in aqueous pyridine at 0 to 50 ° C, with saltpetre acid in glacial acetic acid at 0 to 20 ° C, with chromic acid in glacial acetic acid or in acetone at 0 to 20 ° C and with sulfuryl chloride in Me ethylene chloride at -70 ° C, the thioether obtained Chlorine complex is expediently with aqueous ethanol hydrolyzed.

For the preparation of a sulfonyl compound of the general For mel I is the oxidation based on a corresponding Sulfinyl compound conveniently with one or more equi valents of the oxidizing agent used or starting from a corresponding mercapto compound expediently with two or more equivalents of the oxidizing agent used performed, e.g. B. with hydrogen peroxide in glacial acetic acid / acetane hydride, trifluoroacetic acid or in formic acid at 20 to 100 ° C or in acetone at 0 to 60 ° C, with a peracid like Performic acid or m-chloroperbenzoic acid in glacial acetic acid, tri fluoroacetic acid, methylene chloride or chloroform at Tempe temperatures between 0 and 60 ° C, with nitric acid in glacial acetic acid 0 to 20 ° C, with chromic acid, sodium periodate or potassium pers ganate in acetic acid, water / sulfuric acid or in acetone at 0 up to 20 ° C.  

The subsequent reduction of a nitro group is preferred wise hydrogenolytically, e.g. B. with hydrogen in the presence a catalyst such as palladium / carbon or Raney nickel in a solvent such as methanol, ethanol, ethyl acetate ester, dimethylformamide, dimethylformamide / acetone or glacial acetic acid optionally with the addition of an acid such as hydrochloric acid or Glacial acetic acid at temperatures between 0 and 50 ° C, preferably however at room temperature and at a hydrogen pressure of 1 to 7 bar, but preferably from 3 to 5 bar.

The subsequent production of an appropriate urea compound of the general formula I is advantageously with an inorganic cyanate or a corresponding isocyanate or carbamoyl chloride, preferably in a solvent such as Dimethylformamide and optionally in the presence of a ter tertiary organic base such as triethylamine at temperatures between 0 and 50 ° C, preferably at room temperature, carried out.

The subsequent production of a corresponding guanidino compound of general formula I is convenient by reaction with one which transfers the amidino group Compound such as 3,5-dimethylpyrazole-1-carboxamide preferably in a solvent such as dimethylformamide and optionally in the presence of a tertiary organic base like triethylamine at temperatures between 0 and 50 ° C, before preferably carried out at room temperature.

In the implementations described above, given if reactive groups such as carboxy, hydroxy, Amino, alkylamino or imino groups during the reaction are protected by usual protective groups, which after the Implementation to be split off again.  

For example, the trimethylsilyl, methyl, ethyl, tert-butyl, benzyl or tetrahydropyranyl group and comes as a protective radical for a carboxy group
as a protective radical for a hydroxyl, amino, alkylamino or imino group, the acetyl, trifluoroacetyl, benzoyl, ethoxycarbonyl, tert.butoxycarbonyl, benzyloxycarbonyl, benzyl, methoxybenzyl or 2,4-dimethoxybenzyl group and for the amino group additionally the phthalyl group into consideration.

The subsequent subsequent splitting off of one used Protective residue takes place, for example, hydrolytically in an aqueous solution Rigen solvent, for. B. in water, isopropanol / water, Te trahydrofuran / water or dioxane / water, in the presence of a Acid such as trifluoroacetic acid, hydrochloric acid or sulfuric acid or in the presence of an alkali base such as lithium hydroxide, natri Umhydroxid or potassium hydroxide at temperatures between 0 and 100 ° C, preferably at temperatures between 10 and 50 ° C.

The removal of a benzyl, methoxybenzyl or benzyloxy However, carbonyl radical is carried out, for example, by hydrogenolysis, e.g. B. with hydrogen in the presence of a catalyst such as Pal ladium / coal in a solvent such as methanol, ethanol, Es ethyl acetate, dimethylformamide, dimethylformamide / acetone or glacial acetic acid, optionally with the addition of an acid such as Hydrochloric acid or glacial acetic acid at temperatures between 0 and 50 ° C, but preferably at room temperature and with water fabric pressure from 1 to 7 bar, but preferably from 3 to 5 bar.

A methoxybenzyl group can also be split off in counter were an oxidizing agent such as cerium (IV) ammonium nitrate in a solvent such as methylene chloride, acetonitrile or ace tonitrile / water at temperatures between 0 and 50 ° C, preferred however, at room temperature.  

However, a 2,4-dimethoxybenzyl radical is split off preferably in trifluoroacetic acid in the presence of anisole.

The cleavage of a tert-butyl or tert-butyloxycarbonyl the rest is preferably done by treatment with an acid such as trifluoroacetic acid or hydrochloric acid optionally under Use of a solvent such as methylene chloride, dioxane, Ethyl acetate or ether.

A phthalyl radical is preferably cleaved in Presence of hydrazine or a primary amine such as methyl amine, ethylamine or n-butylamine in a solvent such as Methanol, ethanol, isopropanol, toluene / water or dioxane Temperatures between 20 and 50 ° C.

Further obtained chiral compounds of the general Formula I in their enantiomers and / or diastereomers be separated.

For example, the compounds obtained from general formula I, which occur in racemates, according to known methods (see Allinger N. L. and Eliel E. L. in "Topics in Stereochemistry", Vol. 6, Wiley Interscience, 1971) in their optical antipodes and connections of the general my formula I with at least 2 asymmetrical carbon atoms due to their physico-chemical differences methods known per se, e.g. B. by chromatography and / or fractional crystallization, in their diastereomers separate which, if they occur in racemic form, on finally, as mentioned above, separated into the enantiomers that can.

The separation of enantiomers is preferably carried out by columns separation on chiral phases or by recrystallization an optically active solvent or by reacting with one with the racemic compound salts or derivatives such as e.g. B. ester or amide-forming optically active substance, in particular  Acids and their activated derivatives or alcohols, and separating the mixture thus obtained reomeric salts or derivatives, e.g. B. due to various Solubilities, being from the pure diastereomeric salts or Derivatives the free antipodes by the action of appropriate Funds can be released. Particularly common, op Table active acids are e.g. B. the D and L forms of wine acid, dibenzoyltartaric acid, di-o-tolyltartaric acid, malic acid, Mandelic acid, camphorsulfonic acid, glutamic acid, N-acetylglu tamic acid, aspartic acid, N-acetyl-aspartic acid or Quinic acid. As an optically active alcohol comes for example (+) - or (-) - menthol and as an optically active acyl residue in Amides, for example, the (+) - or (-) - menthyloxycarbonyl radical into consideration.

Furthermore, the compounds of formula I obtained in their salts, especially for pharmaceutical use in their physiologically compatible salts with inorganic or organic acids. Come as acids for this, for example hydrochloric acid, hydrobromic acid, Schwe rock acid, phosphoric acid, fumaric acid, succinic acid, milk acid, citric acid, tartaric acid, maleic acid or methanesul fonic acid into consideration.

In addition, the new compounds of Formula I, if they contain a carboxy group, desired if necessary then in their salts with inorganic or ganic bases, especially for pharmaceutical applications convert them into their physiologically acceptable salts. The bases here are, for example, sodium hydroxide, Ka lium hydroxide, cyclohexylamine, ethanolamine, diethanolamine and Triethanolamine into consideration.

Some of the compounds of general formulas VII to XII used as starting products are known from the literature or can be obtained by processes known from the literature or can be obtained by the processes described above and in the examples. For example, the compounds of general formula IX are described in German patent application 198 24 922.5. Furthermore, the compounds of the general XI are accessible from the compounds of the general formula I in which R _{4 is} a C _1-4 -alkylphenyl group substituted in the alkyl part by a hydroxyl group, for example by reaction with alkyl or arylsulfonyl chlorides.

As already mentioned at the beginning, the new compounds of the general formula I, in which R _{1 represents} a hydrogen atom or a prodrug residue, have valuable pharmacological properties, in particular an inhibitory effect on various kinases, especially on receptor tyrosine kinases such as VEGFR2,. PDGFRα, PDGFRβ, FGFR1, FGFR3, EGFR, HER2, IGF1R and HGFR, as well as on complexes of CDK's (Cyclin Dependent Kinases) such as CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8 and CDK9 with their specific cyclins (A , B1, B2, C, D1, D2, D3, E, F, G1, G2, H, I and K) and on viral cyclin, on the proliferation of cultured human cells, especially those of endothelial cells, e.g. B. in angiogenesis, but also on the proliferation of other cells, especially tumor cells.

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

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

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

The compounds of the invention were in 100% dimethyl sulfoxide dissolved and in different dilutions as three technical provisions added to the cultures, the maximum Dimethyl sulfoxide concentration was 0.3%.

The cells were incubated for 76 hours at 37 ° C., then ³ H-thymidine (0.1 μCi / well, Amer sham) was added for a further 16 hours in order to determine the DNA synthesis. The radioactively labeled cells were then immobilized on filter mats and the radioactivity incorporated was determined in a β-counter. To determine the inhibitory activity of the compounds according to the invention, the mean value of the non-stimulated cells was subtracted from the mean value of the factor-stimulated cells (in the presence or absence of the compounds according to the invention).

The relative cell proliferation was calculated as a percentage of the control (HUVEC without inhibitor) and the active ingredient concentration, which inhibits cell proliferation by 50% (IC ₅₀ ), was derived.

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

• a) 3-Z- [1- (4- (Piperidin-1-ylmethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone,  
• b) 3-Z - [(1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylme ethylene] -6-carbamoyl-2-indolinone,
• c) 3-Z- [1- (4- (Piperidin-1-ylmethyl) anilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone,
• d) 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone,
• e) 3-Z- [1- (4 - ((2,6-dimethylpiperidin-1-yl) methyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• f) 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-acetylamino) -ani lino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• g) 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) -ani lino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• h) 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonyl-ami no) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• i) 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethyl leni-6-methoxycarbonyl-2-indolinone,
• j) 3-Z- [1- (4- (N-acetyl-N-dimethylaminocarbonylmethylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,
• k) 3-Z- [1- (4-ethylaminomethyl-anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone,
• l) 3-Z- [1- (4- (1-methylimidazol-2-yl) anilino) -1-phenylme ethylene] -6-methoxycarbonyl-2-indolinone,
• m) 3-Z- [1- (4- (N-dimethylaminomethylcarbonyl-N-methylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,  
• n) 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonyl-ami no) -anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,
• o) 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-methylsulfonyl amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indo linon,
• p) 3-Z- [1- (4- (N-Dimethylaminocarbonylmethyl-N-methylsulfonyl amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indoli non,
• q) 3-Z- [1- (4- (N - ((2-Dimelhylaminoethyl) carbonyl) -N-methyl amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indo linon,
• r) 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-acetylamino) -ani lino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone and
• s) 3-Z- [1- (4-methylaminomethyl-anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone.

The following table contains the results found:

Because of their inhibitory effect on cell proliferation, especially of endothelial cells and tumor cells the compounds of general formula I for treatment of diseases in which the proliferation of cells, esp especially that of endothelial cells, plays a role.

For example, the proliferation of endothelial cells and the associated neovascularization makes a difference the next step in tumor progression (Folkman J. et al., Nature 339, 58-61, (1989); Hanahan D. and Folkman J., Cell 86, 353-365, (1996)). The proliferation of Endothelial cells also in hemangiomas, in metastasis, rheumatoid arthritis, psoriasis and ocular Neovascularization of importance (Folkman J., Nature Med. 1, 27-31, (1995)). The therapeutic benefit of inhibitors of Endothelial cell proliferation was used in the animal model, for example by O'Reilly et al. and Parangi et al. shown (O'Reilly M. S. et al., Cell 88, 277-285, (1997); Parangi S. et al., Proc Natl Acad Sci USA 93, 2002-2007, (1996)).

The compounds of the general formula I, their tautomers, their stereoisomers or their physiologically acceptable ones Salts are therefore suitable, for example, for the treatment of Tumors (e.g. squamous cell carcinoma, astrocytoma, Kahosi's Sarcoma, glioblastoma, lung cancer, bladder cancer, cervical and Neck carcinoma, melanoma, ovarian carcinoma, prostate carcinoma, Breast cancer, small cell lung cancer, glioma, colorectal carcinoma, urogenital cancer and gastrointestinal carcinoma as well haematological cancers, such as multiple myeloma),  Psoriasis, arthritis (e.g. rheumatoid arthritis), Häman gioma, angiofibroma, eye diseases (e.g. diabetic Retinopathy), neovascular glaucoma, kidney disease (e.g. Glomerulonephritis), diabetic nephropathy, malignant Nephrosclerosis, thrombic microangiopathic syndromes, Transplant rejection and glomerulopathy, fibrotic Diseases (e.g. cirrhosis of the liver), mesangial cell proliferative Diseases, atherosclerosis, nerve tissue injuries and to inhibit reocclusion of vessels after balloon catheter treatment, in vascular prosthetics or after Use of mechanical devices to keep open Vessels (e.g. stents), or other diseases in which Cell proliferation or angiogenesis play a role.

Due to their biological properties, inventions compounds according to the invention alone or in combination with whose pharmacologically active compounds are used den, for example in tumor therapy in monotherapy or in combination with other anti-tumor therapeutic agents, for example in combination with topoisomerase inhibitors (e.g. Eto poside), mitosis inhibitors (e.g. vinblastine, taxol), with nu compounds interacting with small acids (e.g. cis-platinum, Cyclophosphamide, adriamycin), hormone antagonists (e.g. Ta moxifene), inhibitors of metabolic processes (e.g. 5-FU etc.), Cytokines (e.g. interferons), kinase inhibitors, antibodies pern, or in combination with radiation therapy etc. This Combinations can be administered either simultaneously or sequentially be enough.

In pharmaceutical application, the fiction moderate connections usually in warm-blooded vertebrates, especially in humans, in doses of 0.01-100 mg / kg Body weight, preferably used at 0.1-20 mg / kg. To These are administered using one or more common methods inert carriers and / or diluents, e.g. B. with Corn starch, milk sugar, cane sugar, microcrystalline cell loose, magnesium stearate, polyvinylpyrrolidone, citric acid,  Tartaric acid, water, water / ethanol, water / glycerin, water / - Sorbitol, water / polyethylene glycol, propylene glycol, stearylal alcohol, carboxymethyl cellulose or fatty substances such as Hard fat or their suitable mixtures in conventional galenic Preparations such as tablets, coated tablets, capsules, powder, injek tion solutions, ampoules, suspensions, solutions, sprays or Suppository incorporated.  

The following examples are intended to illustrate the invention purify:

used abbreviations

FMOC = 9-fluorenylmethoxycarbonyl
HOBt = 1-hydroxy-1H-benzotriazole
TBTU = O-benzotriazol-1-yl-N, N, N ', N'-tetramethyluronium tetrafluoroborate
DBU = 1,8-diazabicyclo [5.4.0] undec-7-ene

Preparation of the starting compounds Solid phase example 1

2.0 g of Rink resin (MBHA resin, Novablochem) is allowed to swell in 30 ml of dimethylformamide. Then 40 ml of 30% piperidine in dimethylformamide are added and the mixture is shaken for 7 minutes in order to remove the FMOC protective group. Then the resin is washed several times with dimethylformamide. Then 0.4 g of 2-indolinone-6-carboxylic acid (prepared analogously to Langenbeck et al., Justus Liebigs Ann. Chem. 499, 201-208 (1932)), 297 mg of HOBt, 706 mg of TBTU and 0.9 ml of N-ethyl diisopropylamine in 30 ml of dimethylformamide and shake for 1 hour. Then the solution is suctioned off and the resin is washed five times with 30 ml of dimethylformamide and three times with 30 ml of methylene chloride. Nitrogen is blown through the resin to dry.
Yield: 1.9 g loaded resin

Solid phase example II

1.9 g of the resin obtained according to Example I are stirred for 3 hours at 110 ° C. with 6 ml of acetic anhydride and 6 ml of triethyl orthobenzoate. Then allowed to cool and the resin washed with dimethylformamide and then with methylene chloride.
Yield: 1.9 g wet resin

The following loaded resins are prepared analogously to Example II:

• 1. Resin coated with 3-Z- (1-ethoxy-methylene) -6-carbamoyl-2-indolinone
  Prepared by reacting the resin obtained according to Example I with triethyl orthoformate
• 2. Resin coated with 3-Z- (1-methoxy-1-methylmethylene) -6-carbamoyl-2-indoline
  Prepared by reacting the resin obtained according to Example I with trimethyl orthoacetic acid
• 3. Resin coated with 3-Z- (1-methoxy-1-ethylmethylene) -6-carbamoyl-2-indoline
  Prepared by reacting the resin obtained according to Example I with trimethyl orthopropionate
• 4. Resin coated with 3-Z- (1-methoxy-1-propylmethylene) -6-carbamoyl-2-indoline
  Prepared by reacting the product from Example I and trimethyl orthobutyrate

Example III N- (4-nitrophenyl) -N-methyl-methanesulfonamide

3.0 g of N-methyl-4-nitroaniline are dissolved in 20 ml of pyridine and 2.4 g of methanesulfonic acid chloride are added dropwise at room temperature. The mixture is stirred for 12 hours at room temperature. After this time, the mixture is poured onto water, the precipitate which has separated out is filtered off and dried at 50 ° C. in vacuo.
Yield: 4.0 g (87% of theory),
R _f value: 0.5 (silica gel, ethyl acetate / toluene = 7: 3)
Melting point: 107-108 ° C

Example IV N- (2-Dimethylamino-ethyl) -N-methylsulfonyl-4-nitroaniline

38.9 g of N-methylsulfonyl-4-nitroaniline are dissolved in 2.0 l of acetone, 51.9 g of 1-chloro-2-dimethylamino-ethane, 77.4 g of potassium carbonate and 5.0 g of sodium iodide are added, and the mixture is stirred for a total of 4 days at 50 ° C. where after 12 hours another 25.9 g of 1-chloro-2-dimethylamino-ethane, 49.8 g of potassium carbonate and 5.0 g of sodium iodide in 500 ml of acetone and after 36 hours of another 26.0 g of 1-chloro-2-dimethylamino-ethane, 50.0 g of potassium carbonate and 5.0 g of sodium iodide in 100 ml of acetone are added. After this time, the mixture is filtered and the filtrate is concentrated. The residue is stirred with ether, suction filtered and dried at 40 ° C.
Yield: 25.3 g (49% of theory),
R _f value: 0.5 (silica gel, methylene chloride / methanol / ammonia = 9: 1: 0.1)
C ₁₁ H ₁₇ N ₃ O ₄ S
ESI mass spectrum: m / z = 288 [M + H ⁺ ]

The following compounds are prepared analogously to Example IV:

• 1. 4- [N- (3-Dimethylamino-propyl) -N-methylsulfonylamino] - nitrobenzene
• 2. N-carboxymethyl-N-methylsulfonyl-4-nitroaniline
• 3. N-cyanomethyl-N-methylsulfonyl-p-phenylenediamine  
• 4. 4- [N- (2- (N-benzyl-N-methylamino) ethyl) -N-methylsulfonyl amino] nitrobenzene
• 5. 4- [N- (3-phthalimido-2-yl-propyl) -N-methylsulfonylamino] - nitrobenzene
• 6. 4- [N- (3- (N-Benzyl-N-methylamino) propyl) -N-methylsul fonylamino] nitrobenzene

Example V N- (dimethylaminocarbonyl-methyl) -N-methylsulfonyl-4-nitro aniline

7.0 g of N-carboxymethyl-N-methylsulfonyl-4-nitroaniline, 2.5 g of dimethylamine hydrochloride, 8.1 g of TBTU and 3.9 g of HOBT are dissolved in 125 ml of dimethylformamide and 17.6 ml of N-ethyl diisopropylamine are added at 0 ° C. The mixture is stirred for 4 hours at room temperature, diluted with 1 l of water and the precipitate which has precipitated is filtered off with suction. After washing with water, ethanol and ether, the residue is dried at 70 ° C in a vacuum.
Yield: 5.3 g (69% of theory),
R _f value: 0.40 (silica gel, methylene chloride / methanol = 9: 1)
C ₁₁ H ₁₅ N ₃ O ₅ S
ESI mass spectrum: m / z = 300 [M - H ^- ]

The following compounds are produced analogously to Example V:

• 1. 4 - [(N-Dimethylaminocarbonylmethyl) amino] nitrobenzene
  Made from 4- (N-carboxymethylamino) nitrobenzene and dimethylamine hydrochloride
• 2. 4- (N-methylaminocarbonylmethyl-N-methylsulfonylamino) nitrobenzene
  Made from N-carboxymethyl-N-methylsulfonyl-4-nitroaniline and methylamine hydrochloride
• 3. 4 - [(N- (Methylcarbamoyl-methyl) -N-methyl-amino) -methyl] - nitrobenzene
  Made from 4 - [(N-carboxymethyl-N-methylamino) methyl] nitrobenzene and methylamine hydrochloride
• 4. 4 - [(N- (Dimethylcarbamoyl-methyl) -N-methyl-amino) -methyl] - nitrobenzene
  Made from 4 - [(N-carboxymethyl-N-methylamino) methyl] nitrobenzene and dimethylamine hydrochloride

Example VI 4- [N- (2-Dimethylamino-ethyl) -N-acetylamino] nitrobenzene

3.6 g of 4- (2-dimethylamino-ethylamino) nitrobenzene (according to Gabbay et al., J. Am. Chem. Soc. 91, 5136 (1969)) are dissolved in 50 ml of methylene chloride and 5.0 ml of triethylamine are added. 1.3 ml of acetyl chloride are slowly added dropwise to this mixture at room temperature and the mixture is stirred at room temperature for 2 hours. After this time, another 5.0 ml of triethylamine and 1.3 ml of acetyl chloride are added and the mixture is refluxed for a further 2 hours. The solvent is stripped off, the residue is taken up in ethyl acetate and the organic phase is extracted twice with water. After drying over MgSO ₄ , the solvent is stripped off and the residue is dried in vacuo.
Yield: 2.0 g (45% of theory),
R _f value: 0.55 (silica gel, methylene chloride / methanol / ammonia = 9: 1: 0.1)
C ₁₂ H ₁₇ N ₃ O ₃
ESI mass spectrum: m / z = 252 [M + H ⁺ ]

The following compounds are prepared analogously to Example VI:

• 1. 4- [N- (3-Dimethylamino-propyl) -N-acetylamino] nitrobenzene
  Made from 4- (3-dimethylamino-propylamino) nitrobenzene (according to Gabbay et al., J. Am. Chem. Soc. 91, 5136 (1969) and acetyl chloride
• 2. 4- [N- (2-Dimethylamino-ethyl) -N-propionylamino] nitrobenzene
  Made from 4- (2-dimethylamino-ethylamino) nitrobenzene and propionyl chloride
• 3. 4- [N-acetyl-N- (dimethylaminocarbonylmethyl) amino] nitrobenzene
  Made from 4- [N- (dimethylaminocarbonylmethyl) amino] nitrobenzene and acetyl chloride
• 4. 4- [N- (2-Dimethylamino-ethyl) -N-butyrylamino] nitrobenzene
  Made from 4- (2-dimethylamino-ethylamino) nitrobenzene and butyryl chloride
• 5. 4- [N- (2-Dimethylaminoethyl) -N-isobutyrylamino] nitrobenzene
  Made from 4- (2-dimethylamino-ethylamino) nitrobenzene and isobutyryl chloride
• 6. 4- [N- (2-Dimethylamino-ethyl) -N-benzoyl-amino] -nitrobenzene
  Made from 4- (2-dimethylamino-ethylamino) nitrobenzene and benzoyl chloride
• 7. 4- [N- (2-Dimethylaminoethyl) -N-acetylamino] -1,3-dinitro benzene
  Made from 4- (2-dimethylamino-ethyl-amino) -1,3-dinitrobenzene and acetyl chloride
• 8. 4- [N- (2-Dimethylaminoethyl) -N- (furan-2-carbonyl) amino] nitrobenzene
  Made from 4- (2-dimethylamino-ethylamino) nitrobenzene and furan-2-carbonyl chloride
• 9. 4- [N- (2-Dimethylamino-ethyl) -N- (2-methoxy-benzoyl) amino] -nitrobenzene
  Made from 4- (2-dimethylamino-ethylamino) nitrobenzene and 2-methoxy-benzoyl chloride
• 10. 4- [N- (2-Dimethylaminoethyl) -N- (pyridine-3-carbonyl) amino] nitrobenzene
  Made from 4- (2-dimethylamino-ethylamino) nitrobenzene and nicotinic acid chloride
• 11. 4- [N- (2-Dimethylaminoethyl) -N- (phenylacetyl) amino] nitrobenzene
  Made from 4- (2-dimethylamino-ethylamino) nitrobenzene and phenylacetyl chloride
• 12. 4- [N- (2-Dimethylaminoethyl) -N-acetylamino] -3-bromo-nitrobenzene
  Made from 4- [N- (2-Dimethylamino-ethyl) -amino] -3-bromo-nitrobenzene and acetyl chloride
• 13. N-Acryloyl-N-methyl-4-nitro-aniline
  Made from 4-methylamino-nitrobenzene and acrylic acid chloride
• 14. N-Acryloyl-N-isopropyl-4-nitro-aniline
  Made from 4-isopropylamino-nitrobenzene and acrylic acid chloride
• 15. N-Acryloyl-N-benzyl-4-nitro-aniline
  Made from 4-benzylamino-nitrobenzene and acrylic acid chloride
• 16. N-bromoacetyl-N-methyl-4-nitro-aniline
  Made from 4-methylamino-nitrobenzene and bromoacetyl chloride
• 17. N-bromoacetyl-N-isopropyl-4-nitro-aniline
  Made from 4-isopropylamino-nitrobenzene and bromoacetyl chloride
• 18. N-bromoacetyl-N-benzyl-4-nitro-aniline
  Made from 4-benzylamino-nitrobenzene and bromoacetyl chloride

Example VII N- (dimethylaminomethylcorbonyl) -N-methyl-4-nitro-aniline

1.8 g of dimethylamine hydrochloride and 5.5 g of potassium carbonate are placed in 80 ml of acetone and 4.2 g of N-bromoacetyl-N-methyl-4-nitroaniline are added in three portions at room temperature. The mixture is stirred for 12 hours at room temperature. After this time the mixture is filtered and the filtrate is concentrated. The residue is dissolved in ethyl acetate, washed twice with water, dried over sodium sulfate and finally evaporated.
Yield: 2.8 g (79% of theory),
R _f value: 0.5 (silica gel, ethyl acetate / methanol = 7: 3)
Melting point: 121-122 ° C

The following compounds are prepared analogously to Example VII:

• 1. N- (piperidin-1-yl-methylcarbonyl) -N-methyl-4-nitroaniline
• 2. N- (morpholin-4-yl-methylcarbonyl) -N-methyl-4-nitroaniline
• 3. N - [(4-benzyl-piperazin-1-yl) methylcarbonyl] -N-methyl-4- nitroaniline
• 4. N- (pyrrolidin-1-yl-methylcarbonyl) -N-methyl-4-nitroaniline
• 5. N - [(N-aminocarbonylmethyl-N-methylamino) methylcarbonyl] - N-methyl-4-nitroaniline
• 6. N - [(N-benzyl-N-methylamino) methylcarbonyl] -N-methyl-4- nitroaniline  
• 7. N- [Di- (2-methoxyethyl) amino-methylcarbonyl] -N-methyl-4- nitroaniline
• 8. N- (Dimethylaminomethylcarbonyl) -N-isopropyl-4-nitro-aniline
• 9. N- (piperidin-1-yl-methylcarbonyl) -N-isopropyl-4-nitro aniline
• 10. N - [(4-tert. 99999 00070 552 001000280000000200012000285919988800040 0002010042696 00004 99880 butoxycarbonyl-piperazin-1-yl) - methylcarbonyl] -N-isopropyl-4-nitro-aniline
• 11. N - [(N-benzyl-N-methylamino) methylcarbonyl] -N-benzyl-4- nitro-aniline
• 12. N- (Dimethylaminomethylcarbonyl) -N-benzyl-4-nitro-aniline
• 13. N- (piperidin-1-yl-methylcarbonyl) -N-benzyl-4-nitro-aniline
• 14. N- [di- (2-hydroxyethyl) amino-methylcarbonyl] -N-methyl-4- nitroaniline
• 15. N - [(N- (2-methoxyethyl) -N-methylamino) methylcarbonyl] -N- methyl-4-nitroaniline
• 16. N - [(N- (2-dimethylaminoethyl) -N-methylamino) - methylcarbonyl] -N-methyl-4-nitroaniline
• 17. N - [(4-methyl-piperazin-1-yl) methylcarbonyl] -N-methyl-4- nitroaniline
• 18. N - [(imidazol-1-yl) methylcarbonyl] -N-methyl-4-nitroaniline
• 19. N - [(Phthalimido-2-yl) methylcarbonyl] -N-methyl-4-nitro aniline

Example VIII N - [(2-dimethylaminoethyl) carbonyl] -N-benzyl-4-nitro-aniline

0.5 g of dimethylamine hydrochloride, 1.1 ml of triethylamine and 1.2 g of N-acryloyl-N-benzyl-4-nitro-aniline are dissolved in 50 ml of methanol and stirred for 24 hours at room temperature. After this time the mixture is concentrated. The residue is purified on an aluminum oxide column (activity 2-3) with methylene chloride / ethanol 50: 1 as the eluent.
Yield: 1.4 g (98% of theory),
R _f value: 0.8 (aluminum oxide, methylene chloride / ethanol = 20: 1)
Melting point: 73 ° C

The following compounds are prepared analogously to Example VIII:

• 1. N - [(2-Dimethylaminoethyl) carbonyl] -N-isopropyl-4-nitro aniline
  Made from N-Acryloyl-N-isopropyl-4-nitro-aniline and dimethylamine hydrochloride
• 2. N - [(2-dimethylaminoethyl) carbonyl] -N-methyl-4-nitro aniline
  Made from N-Acryloyl-N-methyl-4-nitro-aniline and dimethylamine hydrochloride
• 3. N - [(2- (4-tert-butoxycarbonyl-piperazin-1-yl) ethyl) carbonyl] -N-methyl-4-nitro-aniline
  Made from N-Acryloyl-N-methyl-4-nitro-aniline and N-tert-butoxycarbonyl-piperazine
• 4. N - [(2- (piperidin-1-yl) ethyl) carbonyl] -N-methyl-4-nitro aniline
  Made from N-Acryloyl-N-methyl-4-nitro-aniline and piperidine
• 5. N - [(2- (N-benzyl-N-methylamino) ethyl) carbonyl] -N-methyl-4-nitro-aniline
  Made from N-Acryloyl-N-methyl-4-nitro-aniline and N-Benzyl-N-methyl-amine

Example IX 4- (4-methyl-piperazin-1-yl) nitrobenzene

31.5 g of 4-chloro-1-nitrobenzene and 44.4 ml of 1-methylpiperazine are combined and stirred at 90 ° C for 18 hours. The solution is then poured onto ice water and the precipitate which has separated out is filtered off with suction, washed with water and recrystallized from ethanol / water 1: 1. The residue is dried in vacuo at 75 ° C.
Yield: 44.0 g (99% of theory),
R _f value: 0.5 (silica gel, methylene chloride / methanol = 10: 1)
Melting point: 108-112 ° C

The following compounds are prepared analogously to Example IX:

• 1. N- (2-Dimethylaminoethyl) -N-methyl-4-nitroaniline
  Made from 1-fluoro-4-nitrobenzene and 1-dimethylamino-2-methylamino-ethane
• 2. N- (3-dimethylaminopropyl) -N-methyl-4-nitroaniline
  Made from 1-fluoro-4-nitrobenzene and 1-dimethylamino-3-methylamino-propane
• 3. 4- (N-carboxymethylamino) nitrobenzene
  Made from 1-fluoro-4-nitrobenzene and glycine
• 4. N-cyclohexyl-p-phenylenediamine
  Made from 1-fluoro-4-nitrobenzene and cyclohexylamine
• 5. 6- [N- (2-Dimethylamino-ethyl) -N-methylsulfonylamino] -3-phthalimido-2-yl-nitrobenzene
  Made from 2-nitro-4-phthalimido-2-yl-fluorobenzene, N- (2-dimethylamino-ethyl) methanesulfonamide and sodium hydride as a base
• 6. 6- [N- (2-Dimethylaminoethyl) -N-methylsulfonylamino] -1,3-dinitrobenzene
  Made from 2,4-dinitro-chlorobenzene, N- (2-dimethylamino ethyl) methanesulfonamide and sodium hydride as a base
• 7. 4- [N- (2-Dimethylamino-ethyl) -N-methylsulfonylamino] -3-chloro-nitrobenzene
  Made from 2-fluoro-5-nitro-chlorobenzene, N- (2-dimethylaminoethyl) methanesulfonamide and sodium hydride as a base
• 8. 4- (2-Dimethylaminoethylamino) -1,3-dinitrobenzene
  Made from 1-chloro-2,4-dinitro-benzene and N, N-dimethyl ethylene diamine
• 9. 4- [N- (2-Dimethylaminoethyl) -N- (ethylsulfonyl) amino] nitrobenzene
  Made from 1-fluoro-4-nitro-benzene, N- (2-dimethylamino ethyl) ethanesulfonamide and sodium hydride as a base
• 10. 4- [N- (2-Dimethylaminoethyl) -N- (propylsulfonyl) amino] - nitrobenzene
  Made from 1-fluoro-4-nitro-benzene, N- (2-dimethylamino ethyl) propane sulfonamide and sodium hydride as a base
• 11. 4- [N- (2-Dimethylaminoethyl) -N- (butylsulfonyl) amino] - nitrobenzene
  Made from 1-fluoro-4-nitro-benzene, N- (2-dimethylamino ethyl) -butanesulfonamide and sodium hydride as a base
• 12. 4- [N- (2-Dimethylaminoethyl) -N- (benzylsulfonyl) amino] - nitrobenzene
  Made from 1-fluoro-4-nitro-benzene, N- (2-dimethylamino ethyl) -C-phenylmethanesulfonamide and sodium hydride as a base
• 13. 4- [N- (2-Dimethylaminoethyl) -N- (phenylsulfonyl) amino] nitrobenzene
  Made from 1-fluoro-4-nitro-benzene, N- (2-dimethylamino ethyl) -benzenesulfonamide and sodium hydride as a base
• 14. 4- [N- (2-Dimethylamino-ethyl) -N- (isopropylsulfonyl) amino] nitrobenzene
  Made from 1-fluoro-4-nitro-benzene, N- (2-dimethylamino ethyl) -isopropylsulfonamide and sodium hydride as a base
• 15. 4- [N- (2-Dimethylaminoethyl) amino] -3-bromo-nitrobenzene
  Made from 2-bromo-1-fluoro-4-nitro-benzene and N, N-dimethylethylene diamine
• 16. 4-isopropylamino-nitrobenzene
  Made from 1-fluoro-4-nitrobenzene and isopropylamine
• 17. 4-Benzylamino-nitrobenzene
  Made from 1-fluoro-4-nitrobenzene and benzylamine

Example X 4- (imidazol-4-yl) nitrobenzene

9.5 g of 2-phenylimidazole are carefully dissolved in 50 ml of concentrated sulfuric acid and 5.8 g of ammonium nitrate are added to this solution at 0 ° C. After stirring for a further 60 minutes at 0 ° C., the batch is poured onto ice water, blown with ammonia water and the precipitate which has separated out is filtered off with suction and recrystallized from ethanol.
Yield: 8.0 g (64% of theory),
R _f value: 0.6 (silica gel, ethyl acetate / ethanol = 10: 1)
C ₉ H ₇ N ₃ O ₂
Mass spectrum: m / z = 189 [M ⁺ ]

The following compounds are produced analogously to Example X:

• 1. 4- (imidazol-2-yl) nitrobenzene
  Made from 4- (imidazol-2-yl) benzene
• 2. 4- (5-methylimidazol-4-yl) nitrobenzene
  Made from 4-methyl-5-phenyl-imidazole (J. Heterocycl. Chem. 1983, 20, 1277-1281)

Example XI 4- (2- (imidazol-4-yl) ethylene) nitrobenzene

1.5 g of 4-nitrobenzaldehyde and 7.45 g of (N-trityl-imidazol-4-yl-methyl) triphenylphosphonium chloride are dissolved in 75 ml of tetra hydrofuran and 3.0 ml of DBU are added dropwise to this solution at room temperature. After stirring for a further 120 minutes at room temperature, the mixture is poured onto water and the precipitate which has separated out is filtered off with suction. The product is taken up in 25 ml of 1N hydrochloric acid and refluxed for 4 hours. After this time, the mixture is neutralized with ammonia water, extracted with ethyl acetate and the organic phase is washed with water, dried over sodium sulfate and evaporated. The residue is purified on a silica gel column using methylene chloride / methanol 10: 1 as the eluent.
Yield: 1.0 g (47% of theory),
R _f value: 0.6 (silica gel, ethyl acetate / ethanol = 10: 1)
Melting point: 185-188 ° C

Example XII 4- (piperidin-1-ylmethyl) nitrobenzene

40.0 g of 4-nitrobenzyl bromide are dissolved in 500 ml of methylene chloride, 51.5 ml of triethylamine are added and 18.3 ml of piperidine are carefully added dropwise. After the exothermic reaction has ended, the mixture is refluxed for a further 30 minutes. After cooling, it is washed with water and the organic phase is dried over sodium sulfate. Finally, the organic phase is concentrated.
Yield: 36.3 g (89% of theory),
R _f value: 0.6 (silica gel, methylene chloride / methanol = 9: 1)
C ₁₂ H ₁₆ N ₂ O ₂
Mass spectrum: m / z = 221 [M ⁺ ]

The following compounds are prepared analogously to Example XII:

• 1. 4 - [(2,6-Dimethyl-piperidin-1-yl) methyl] nitrobenzene
• 2. 3- (N, N-Dimethylaminomethyl) nitrobenzene
• 3. 4- (N, N-dimethylaminomethyl) nitrobenzene
• 4. 4- (2-dimethylamino-ethyl) nitrobenzene
• 5. 4- (2-diethylamino-ethyl) nitrobenzene
• 6. 4- (diethylamino-methyl) nitrobenzene
• 7. 4- (N-Benzyl-N-methylaminomethyl) nitrobenzene
• 8. 4- (N-ethyl-N-methylaminomethyl) nitrobenzene
• 9. 4- [N- (n-Hexyl) -N-methylaminomethyl] nitrobenzene
• 10. 4- (Thiomorpholin-4-yl-methyl) nitrobenzene
• 11. 4 - [(4-Methylpiperazin-1-yl) methyl] nitrobenzene
• 12. 4- (imidazol-1-ylmethyl) nitrobenzene
• 13. 4- [2- (4-Hydroxy-piperidin-1-yl) ethyl amino] nitrobenzene
• 14. 4 - [(3-Hydroxy-pyrrolidin-1-yl) methyl] nitrobenzene
• 15. 4- (1,2,4-triazol-1-ylmethyl) nitrobenzene
• 16. 4- (1,2,3-triazol-2-ylmethyl) nitrobenzene
• 17. 4- (1,2,3-triazol-1-ylmethyl) nitrobenzene  
• 18. 4 - [(N-ethoxycarbonylmethyl-N-methylamino) methyl] - nitrobenzene
• 19. 4 - [(N-aminocarbonylmethyl-N-methylamino) methyl] - nitrobenzene
• 20. 4- (Azetidin-1-ylmethyl) nitrobenzene
• 21. 4 - [(Di- (2-methoxyethyl) amino) methyl] nitrobenzene
• 22. 4- [N- (N-tert-butoxycarbonyl-3-aminopropyl) -N-methyl- aminomethyl] nitrobenzene
• 23. 4 - [(N-Propyl-N-methylamino) methyl] nitrobenzene
• 24. 4 - [(N- (2-Dimethylamino-ethyl) -N-methyl-amino) -methyl] - nitrobenzene
• 25. 4 - [(N- (3-Dimethylamino-propyl) -N-methylamino) methyl] - nitrobenzene
• 26. 4 - [(N- (2-methoxyethyl) -N-methylamino) methyl] - nitrobenzene
• 27. 4 - [(N- (2-Hydroxyethyl) -N-methylamino) methyl] nitro benzene
• 28. 4 - [(N- (Dioxolan-2-ylmethyl) -N-methylamino) methyl] - nitrobenzene
• 29. 4- (3-oxopiperazin-1-ylmethyl) nitrobenzene

Example XIII 4 - [(N-Carboxymethyl-N-methylamino) methyl] nitrobenzene

7.33 g of 4 - [(N-ethoxycarbonylmethyl-N-methylamino) methyl] nitrobenzene are dissolved in 140 ml of ethanol, 34.0 ml of 1N sodium hydroxide solution are added and the mixture is stirred for half an hour at room temperature. After this time, the mixture is neutralized with 34 ml of 1N hydrochloric acid, the solvent is stripped off, the residue is taken up in methylene chloride and extracted with water. The aqueous phase is concentrated and the residue is recrystallized from methylene chloride.
Yield: 5.43 g (84% of theory),
R _f value: 0.4 (silica gel, methylene chloride / methanol = 2: 1)
C ₁₀ H ₁₂ N ₂ O ₄
Mass spectrum: m / z = 223 [M ⁺ ]

Example XIV 4- (N-ethylaminomethyl) nitrobenzene

6.0 g of 4-nitrobenzyl bromide are dissolved in 25 ml of ethanol, mixed with 25 ml of 10% ethanolic ethylamine solution and boiled under reflux for 2 hours. Then the solution is rotated, the residue taken up with methylene chloride and washed with dilute sodium hydroxide solution. Finally, the organic phase is concentrated.
Yield: 2.3 g (46% of theory),
R _f value: 0.2 (silica gel, methylene chloride / methanol = 9: 1)
C ₉ H ₁₂ N ₂ O ₂
ESI mass spectrum: m / z = 179 [M - H ^- ]

The following compounds are produced analogously to Example XIV:

• 1. 4- [N- (4-chlorobenzyl) aminomethyl] nitrobenzene
• 2. 4- (N-Cyclohexylaminomethyl) nitrobenzene
• 3. 4- (N-isopropylaminomethyl) nitrobenzene
• 4. 4- (N-propylaminomethyl) nitrobenzene
• 5. 4- (N-methylaminomethyl) nitrobenzene  
• 6. 4- (N-butylaminomethyl) nitrobenzene
• 7. 4- (N-methoxycarbonylmethylaminomethyl) nitrobenzene
• 8. 4- (N-benzylaminomethyl) nitrobenzene
• 9. 4- (aminomethyl) nitrobenzene
• 10. 4- (pyrrolidin-1-ylmethyl) nitrobenzene
• 11. 4- (morpholin-4-ylmethyl) nitrobenzene
• 12. 4- (Hexamethyleneiminomethyl) nitrobenzene
• 13. 4- (4-Hydroxy-piperidin-1-ylmethyl) nitrobenzene
• 14. 4- (4-methoxy-piperidin-1-ylmethyl) nitrobenzene
• 15. 4- (4-methylpiperidin-1-ylmethyl) nitrobenzene
• 16. 4- (4-ethyl-piperidin-1-ylmethyl) nitrobenzene
• 17. 4- (4-isopropyl-piperidin-1-ylmethyl) nitrobenzene
• 18. 4- (4-phenylpiperidin-1-ylmethyl) nitrobenzene
• 19. 4- (4-Benzylpiperidin-1-ylmethyl) nitrobenzene
• 20. 4- (4-ethoxycarbonyl-piperidin-1-ylmethyl) nitrobenzene
• 21. 4- (N, N-Dipropylaminomethyl) nitrobenzene
• 22. 4- (4-tert-butoxycarbonyl-piperazin-1-yl-methyl) - nitrobenzene
• 23. 4- (2-morpholin-4-yl-ethyl) nitrobenzene  
• 24. 4- (2-pyrrolidin-1-yl-ethyl) nitrobenzene
• 25. 4- (2-piperidin-1-yl-ethyl) nitrobenzene
• 26. 4- (N-ethyl-N-benzylaminomethyl) nitrobenzene
• 27. 4- (N-Propyl-N-benzylaminomethyl) nitrobenzene
• 28. 4- [N-Methyl-N- (4-chlorobenzyl) aminomethyl] nitrobenzene
• 29. 4- [N-Methyl-N- (4-bromobenzyl) aminomethyl] nitrobenzene
• 30. 4- [N-Methyl-N- (4-fluorobenzyl) aminomethyl] nitrobenzene
• 31. 4- [N-Methyl-N- (4-methylbenzyl) aminomethyl] nitrobenzene
• 32. 4- [N-Methyl-N- (3-chlorobenzyl) aminomethyl] nitrobenzene
• 33. 4- [N-Methyl-N- (3,4-dimethoxybenzyl) aminomethyl] - nitrobenzene
• 34. 4- [N-Methyl-N- (4-methoxybenzyl) aminomethyl] nitrobenzene
• 35. 4- (N-2,2,2-trifluoroethyl-N-benzylaminomethyl) - nitrobenzene
• 36. 4- [N-2,2,2-trifluoroethyl-N- (4-chlorobenzyl) aminomethyl] - nitrobenzene
• 37. 4- (Thiomorpholin-4-ylmethyl) nitrobenzene
• 38. 4- (Azetidion-1-yl-methyl) nitrobenzene
• 39. 4- (3,4-Dihydropyrrolidin-1-ylmethyl) nitrobenzene
• 40. 4- (3,4-Dihydropiperidin-1-ylmethyl) nitrobenzene  
• 41. 4- (2-Methoxycarbonyl-pyrrolidin-1-yl-methyl) -nitrobenzene
• 42. 4- (3,5-Dimethylpiperidin-1-ylmethyl) nitrobenzene
• 43. 4- (4-phenylpiperazin-1-ylmethyl) nitrobenzene
• 44. 4- (4-phenyl-4-hydroxy-piperidin-1-ylmethyl) nitrobenzene
• 45. 4- [N- (3,4,5-Trimethoxybenzyl-N-methylaminomethyl) - nitrobenzene
• 46. 4- [N- (3,4-Dimethoxybenzyl) -N-ethylaminomethyl] - nitrobenzene
• 47. 4- [N- (2,6-dichlorobenzyl) -N-methyl) aminomethyl] - nitrobenzene
• 48. 4- [N- (4-Trifluoromethylbenzyl) -N-methyl) aminomethyl] - nitrobenzene
• 49. 4- (N-Benzyl-N-isopropylaminomethyl) nitrobenzene
• 50. 4- (N-Benzyl-N-tert.butylaminomethyl) nitrobenzene
• 51. 4- (N, N-Diisopropylaminomethyl) nitrobenzene
• 52. 4- (N, N-Diisobutylaminomethyl) nitrobenzene
• 53.4- (2,3,4,5-Tetrahydro-benzo (d) azepin-3-yl-methyl) - nitrobenzene
• 54. 4- (2,3-Dihydro-isoindol-2-ylmethyl) nitrobenzene
• 55. 4- (6,7-Dimethoxy-1,2,3,4-tetrahydro-isoquinolin-2-yl- methyl) nitrobenzene  
• 56. 4- (1,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) nitro benzene
• 57. 4- [N- (2-Hydroxyethyl) -N-benzylaminomethyl] nitrobenzene
• 58. 4- [N- (1-Ethylpentyl) -N- (pyridin-2-ylmethyl) amino methyl] nitrobenzene
• 59. 4- (Piperin-1-yl-methyl) -1,3-dinitrobenzene
• 60. 4- (N-phenethyl-N-methylaminomethyl) nitrobenzene
• 61. 4- [N- (3,4-Dihydroxyphenethyl) -N-methylaminomethyl] - nitrobenzene
• 62. 4- [N- (3,4,5-Trimethoxyphenethyl) -N-methylaminomethyl] - nitrobenzene
• 63. 4- [N- (3,4-Dimethoxy-phenethyl) -N-methylaminomethyl] - nitrobenzene
• 64. 4- [N- (3,4-Dimethoxybenzyl) -N-methylaminomethyl] - nitrobenzene
• 65. 4- [N- (4-Chlorobenzyl) -N-methylaminomethyl] nitrobenzene
• 66. 4- [N- (4-Bromo-benzyl) -N-methylaminomethyl] nitrobenzene
• 67. 4- [N- (4-Fluoro-benzyl) -N-methylaminomethyl] nitrobenzene
• 68. 4- [N- (4-Methylbenzyl) -N-methylaminomethyl] nitrobenzene
• 69. 4- [N- (4-nitro-phenethyl) -N-methylaminomethyl] - nitrobenzene
• 70. 4- (N-phenethyl-N-benzylaminomethyl) nitrobenzene  
• 71. 4- (N-phenethyl-N-cyclohexylaminomethyl) nitrobenzene
• 72. 4- [N- (2- (pyridin-2-yl) ethyl) -N-methylaminomethyl] - nitrobenzene
• 73. 4- [N- (2- (pyridin-4-yl) ethyl) -N-methylaminomethyl] - nitrobenzene
• 74. 4- [N- (pyridin-4-yl-methyl) -N-methyl-aminomethyl] - nitrobenzene
• 75. 4- (N, N-Dibenzylaminomethyl) nitrobenzene
• 76. 4- [N- (4-nitro-phenethyl) -N-propylaminomethyl] - nitrobenzene
• 77. 4- (N-Benzyl-N- (3-cyano-propyl) aminomethyl) nitrobenzene
• 78. 4- (N-Benzyl-N-allyl aminomethyl) nitrobenzene
• 79. 4- [N-Benzyl-N- (2,2,2-trifluoroethyl) aminomethyl] - nitrobenzene
• 80. 4- [N- (2-Benzo (1,3) dioxol-5-yl-methyl) -N-methyl- aminomethyl] nitrobenzene
• 81. 4- (7-chloro-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl- methyl) nitrobenzene
• 82. 4- (7,8-dichloro-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl- methyl) nitrobenzene
• 83. 4- (7-methoxy-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl- methyl) nitrobenzene
• 84. 4- (7-Methyl-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl- methyl) nitrobenzene  
• 85. 4- (7,8-Dimethoxy-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl- methyl) nitrobenzene
• 86. 4- (6,7-dichloro-1,2,3,4-tetrahydro-isoquinolin-2-yl- methyl) nitrobenzene
• 87. 4- (6,7-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-2-yl- methyl) nitrobenzene
• 88. 4- (6-chloro-1,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) - nitrobenzene
• 89. 4- (7-chloro-1,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) - nitrobenzene
• 90. 4- (6-methoxy-1,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) - nitrobenzene
• 91. 4- (7-methoxy-1,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) - nitrobenzene
• 92.4 - [(2,3,4,5-tetrahydro-azepino (4,5-b) pyrazin-3-yl) - methyl] nitrobenzene
• 93.4 - [(7-amino-2,3,4,5-tetrahydro-azepino (4,5-b) pyrazine-3- yl) methyl] nitrobenzene
• 94.4 - [(2-amino-5,6,7,8-tetrahydro-azepino (4,5-d) thiazole-6- yl) methyl nitrobenzene
• 95.4 - [(5,6,7,8-tetrahydro-azepino (4,5-d) thiazol-6-yl) - methyl] nitrobenzene

Example XV 4- (1,1-dioxothiomorpholin-4-ylmethyl) nitrobenzene

6.0 g of 4- (thiomorpholin-4-yl-methyl) -nitrobenzene are dissolved in 100 ml of methylene chloride and 10.3 g of meta-chloroperbenzoic acid are slowly added. After stirring for a further 3 hours at room temperature, the precipitate obtained is filtered off.
Yield: 6.2 g (91% of theory)
R _f value: 0.5 (silica gel, methylene chloride / methanol = 1: 1)
C ₁₁ H ₁₄ N ₂ O ₄ S
Mass spectrum: m / z = 270 [M ⁺ ]

The following connection is established analogously to Example XV:

• 1. 4- (1-oxothiomorpholin-4-ylmethyl) nitrobenzene

Example XVI 4- [N- (3-aminopropyl) -N-methylsulfonylamino] nitrobenzene

9.5 g of 4- [N- (3-phthalimido-2-yl-propyl) -N-methylsulfonylamino] -nitrobenzene are dissolved in 200 ml of ethanol, 11.5 ml of hydrazine hydrate are added and the mixture is stirred at 50 ° C. for 1.5 hours. After cooling, the residue is largely concentrated, water is added and the solution is extracted with methylene chloride. The organic phase is dried, concentrated and purified over a silica gel column with methylene chloride / methanol / ammonia 9: 1: 0.1.
Yield: 2.5 g (39% of theory)
R _f value: 0.2 (silica gel, methylene chloride / methanol = 9: 1)
C ₁₀ H ₁₅ N ₃ O ₄ S
ESI mass spectrum: m / z = 272 [M - W ^- ]

The following connection is established analogously to Example XVI:

• 1. 6- [N- (2-Dimethylamino-ethyl) -N-methylsulfonylamino] -3-amino-nitrobenzene
  Made from 6- [N- (2-Dimethylamino-ethyl) -N-methylsulfonylamino] -3-phthalimido-2-yl-nitrobenzene

Example XVII 4- (1-methylimidazol-2-yl) nitrobenzene

7.5 g of 4- (imidazol-2-yl) nitrobenzene are dissolved in 50 ml of dimethyl sulfoxide and 5.0 g of potassium tert-butoxide are added at 0 ° C. After stirring for one hour at room temperature, 2.6 ml of methyl iodide are added dropwise and the mixture is stirred for one hour at room temperature. After this time, the residue is poured onto ice water and the precipitate formed is suction filtered, washed with water and dried.
Yield: 6.1 g (76% of theory)
R _f value: 0.6 (silica gel, methylene chloride / methanol = 10: 1)
Melting point: 186-187 ° C

The following compounds are prepared analogously to Example XVII:

• 1. 4- (1-ethyl-imidazol-2-yl) nitrobenzene
  Made from 4- (imidazol-2-yl) nitrobenzene and ethyl iodide
• 2. 4- (1-benzyl-imidazol-2-yl) nitrobenzene
  Made from 4- (imidazol-2-yl) nitrobenzene and benzyl bromide

Example XVIII 4 - [(N- (2- (2-methoxyethoxy) ethyl) -N-methylamino) methyl] - nitrobenzene

5.0 g of 4-methylaminomethyl-nitrobenzene are dissolved in 30 ml of dimethylformamide and 4.6 g of 2- (2-methoxy-ethoxy) ethyl chloride are added. After stirring for six hours at 100 ° C., the solvent is stripped off and the residue is taken up in ethyl acetate. The organic phase is washed with water and dried over sodium sulfate. After the solvent has been stripped off, the residue is purified on an alumina column (activity 2-3) using toluene / ethyl acetate 5: 1 as the eluent.
Yield: 2.3 g (29% of theory)
R _f value: 0.5 (aluminum oxide, toluene / ethyl acetate = 5: 1)
C ₁₃ H ₂₀ N ₂ O ₄
ESI mass spectrum: m / z = 267 [M - H ^- ]

Example XIX 4- (N-ethyl-N-tert.butoxycarbonylaminomethyl) nitrobenzene

2.2 g of 4- (ethylaminomethyl) nitrobenzene are dissolved in 50 ml of acetic ester and stirred with 2.6 g of di-tert-butyl dicarbonate (tert-butoxycarbonyl-anhydride) for 30 minutes at room temperature. The solution is then washed with water and concentrated.
Yield: 3.4 g of theory
R _f value: 0.3 (silica gel, methylene chloride / methanol = 50: 1)
Melting point: 85 ° C

The following connections are made analogously to Example XIX:

• 1. 4- [N- (4-chlorophenylmethyl) -N-tert.butoxycarbonylamino thyl] nitrobenzene
• 2. 4- (N-tert-butoxycarbonylaminomethyl) nitrobenzene
• 3. 4- (N-cyclohexyl-N-tert.butoxycarbonylaminomethyl) - nitrobenzene
• 4. 4- (N-isopropyl-N-tert.butoxycarbonylaminomethyl) - nitrobenzene
• 5. 4- (N-methyl-N-tert.butoxycarbonylaminomethyl) nitrobenzene
• 6. 4- (N-Propyl-N-tert.butoxycarbonylaminomethyl) nitrobenzene
• 7. 4- (N-Butyl-N-tert.butoxycarbonylaminomethyl) nitrobenzene  
• 8. 4- (N-methoxycarbonylmethyl-N-tert.butoxycarbonyl-amino methyl) nitrobenzene
• 9. 4- (N-Benzyl-N-tert.butoxycarbonylaminomethyl) nitrobenzene
• 10. 4- [N- (3-Trifluoroacetylamino-propyl) -N-methylsulfonylamino] nitrobenzene
  Made from 4- [N- (3-aminopropyl) -N-methylsulfonylamino] nitrobenzene and trifluoroacetic anhydride
• 11. 4 - [(4-tert-butoxycarbonyl-piperazin-1-yl) methyl] - nitrobenzene

Example XX 4- (piperidin-1-ylmethyl) aniline

37.0 g of 4- (piperidin-1-ylmethyl) nitrobenzene are dissolved in 300 ml of methanol, 8.0 g of Raney nickel are added and the mixture is hydrogenated at room temperature with 3 bar of hydrogen for 85 minutes. The catalyst is filtered off and the filtrate is evaporated.
Yield: 24.0 g (75% of theory),
R _f value: 0.4 (silica gel, methylene chloride / methanol = 9: 1)
C ₁₂ H ₁₈ N ₂
ESI mass spectrum: m / z = 191 [M + H ⁺ ]

The following compounds are prepared analogously to Example VIII:

• 1.4 - [(2,6-dimethyl-piperidin-1-yl) methyl] aniline
• 2. N- (2-Dimethylamino-ethyl) -N-methylsulfonyl-p-phenylene diamine
• 3. 3- (Dimethylaminomethyl) aniline
• 4. 4- (dimethylaminomethyl) aniline  
• 5. 4- (2-dimethylaminoethyl) aniline
• 6. 4- [N- (2-Dimethylamino-ethyl) -N-acetylamino] aniline
• 7. 4- [N- (3-Dimethylamino-propyl) -N-acetylamino] aniline
• 8. 4- [N- (2-Dimethylamino-ethyl) -N-benzoyl-amino] aniline
• 9. 4- [N- (2-Dimethylaminoethyl) -N-propionylamino] aniline
• 10. 4- [N- (2-Dimethylaminoethyl) -N-butyrylamino] aniline
• 11. 4- [N- (2-Dimethylamino-ethyl) -N-isobutyrylamino] aniline
• 12. 4- (N-tert-butoxycarbonylaminomethyl) aniline
• 13. 4- (N-ethyl-N-tert.butoxycarbonylaminomethyl) aniline
• 14. 4- [N- (4-chlorophenylmethyl) -N-tert.butoxycarbonyl aminomethyl] aniline
• 15. 4- (N-Cyclohexyl-N-tert.butoxycarbonylaminomethyl) aniline
• 16. 4- (N-isopropyl-N-tert.butoxycarbonylaminomethyl) aniline
• 17. 4- (N-Propyl-N-tert.butoxycarbonylaminomethyl) aniline
• 18. 4- (N-Methyl-N-tert-butoxycarbonylaminomethyl) aniline
• 19. 4- (N-Butyl-N-tert.butoxycarbonylaminomethyl) aniline
• 20. 4- (N-methoxycarbonyl-methyl-N-tert.butoxycarbonyl- aminomethyl) aniline
• 21. 4- (N-Benzyl-N-tert.butoxycarbonylaminomethyl) aniline
• 22. 4- (pyrrolidin-1-ylmethyl) aniline  
• 23. 4- (morpholin-4-ylmethyl) aniline
• 24. 4- (hexamethyleneiminomethyl) aniline
• 25. 4- (4-Hydroxy-piperidin-1-ylmethyl) aniline
• 26. 4- (4-methoxy-piperidin-1-ylmethyl) aniline
• 27. 4- (4-methylpiperidin-1-ylmethyl) aniline
• 28. 4- (4-ethyl-piperidin-1-yl-methyl) aniline
• 29. 4- (4-isopropylpiperidin-1-ylmethyl) aniline
• 30. 4- (4-phenylpiperidin-1-ylmethyl) aniline
• 31. 4- (4-Benzylpiperidin-1-ylmethyl) aniline
• 32. 4- (4-ethoxycarbonyl-piperidin-1-ylmethyl) aniline
• 33. 4- (N, N-Dipropylaminomethyl) aniline
• 34. 4- (4-tert-Butoxycarbonyl-piperazin-1-yl-methyl) -aniline
• 35. 4- (2-Morpholin-4-yl-ethyl) aniline
• 36. 4- (2-pyrrolidin-1-yl-ethyl) aniline
• 37. 4- (2-piperidin-1-yl-ethyl) aniline
• 38. 4- (N-Propyl-N-benzylaminomethyl) aniline
• 39. 4- [N- (n-Hexyl) -N-methylaminomethyl] aniline
• 40. 4- [N-Methyl-N- (4-chlorobenzyl) aminomethyl] aniline  
• 41. 4- [N-Methyl-N- (4-bromobenzyl) aminomethyl] aniline
• 42. 4- [N-Methyl-N- (4-methylbenzyl) aminomethyl] aniline
• 43. 4- [N-Methyl-N- (4-fluorobenzyl) aminomethyl] aniline
• 44. 4- [N-Methyl-N- (3-chlorobenzyl) aminomethyl] aniline
• 45. 4- [N-Methyl-N- (3,4-dimethoxybenzyl) aminomethyl] aniline
• 46. 4- [N-Methyl-N- (4-methoxybenzyl) aminomethyl] aniline
• 47. 4- (N-2,2,2-Trifluoroethyl-N-benzylaminomethyl) aniline
• 48. 4- [N-2,2,2-trifluoroethyl-N- (4-chlorobenzyl) aminomethyl] - aniline
• 49. 4- (Thiomorpholin-4-ylmethyl) aniline
• 50. 4- (1-oxothiomorpholin-4-ylmethyl) aniline
• 51. 4- (1,1-Dioxothiomorpholin-4-ylmethyl) aniline
• 52. 4- (Azetidion-1-ylmethyl) aniline
• 53. 4- (3,4-Dihydropyrrolidin-1-ylmethyl) aniline
• 54. 4- (3,4-Dihydropiperidin-1-ylmethyl) aniline
• 55. 4- (2-Methoxycarbonyl-pyrrolidin-1-yl-methyl) aniline
• 56. 4- (3,5-Dimethyl-piperidin-1-yl-methyl) aniline
• 57. 4- (4-phenylpiperazin-1-ylmethyl) aniline
• 58. 4- (4-phenyl-4-hydroxy-piperidin-1-ylmethyl) aniline  
• 59. 4- [N- (3,4,5-Trimethoxybenzyl) -N-methylaminomethyl] - aniline
• 60. 4- [N- (3,4-Dimethoxy-benzyl) -N-ethylaminomethyl] aniline
• 61. 4- (N-Benzyl-N-ethylaminomethyl) aniline
• 62. 4- [N- (2,6-dichlorobenzyl) -N-methylaminomethyl] aniline
• 63. 4- [N- (4-Trifluoromethylbenzyl) -N-methylaminomethyl] - aniline
• 64. 4- (N-Benzyl-N-isopropylaminomethyl) aniline
• 65. 4- (N-Benzyl-N-tert.butylaminomethyl) aniline
• 66. 4- (Diethylamino-methyl) aniline
• 67. 4- (2-Diethylamino-ethyl) aniline
• 68. 4- (N, N-Diisopropylaminomethyl) aniline
• 69. 4- (N, N-Diisobutylaminomethyl) aniline
• 70. 4- (2,3,4,5-tetrahydro-benzo (d) azepin-3-yl-methyl) aniline
• 71. 4- (2,3-Dihydro-isoindol-2-ylmethyl) aniline
• 72. 4- (6,7-Dimethoxy-1,2,3,4-tetrahydro-isoquinolin-2-yl- methyl) aniline
• 73. 4- (1,2,3,4-tetrahydro-isoquinolin-2-ylmethyl) aniline
• 74. 4- [N- (2-Hydroxyethyl) -N-benzylaminomethyl] aniline
• 75. 4- [N- (1-ethylpentyl) -N- (pyridin-2-ylmethyl) - aminomethyl] aniline  
• 76. 4- (Piperidin-1-yl-methyl) -3-nitro-aniline
• 77. 4- (Piperidin-1-yl-methyl) -3-amino-aniline
• 78. 4- (N-Benzyl-N-methylaminomethyl) aniline
• 79. 4- (N-Ethyl-N-methylaminomethyl) aniline
• 80. 4- (N-phenethyl-N-methylaminomethyl) aniline
• 81. 4- [N- (3,4-Dihydroxy-phenethyl) -N-methylaminomethyl] - aniline
• 82. 4- [N- (3,4,5-Trimethoxyphenethyl) -N-methylaminomethyl] - aniline
• 83. 4- [N- (3,4-Dimethoxyphenethyl) -N-methylaminomethyl] - aniline
• 84. 4- [N- (3,4-Dimethoxy-benzyl) -N-methylaminomethyl] aniline
• 85. 4- [N- (4-Chloro-benzyl) -N-methylaminomethyl] aniline
• 86. 4- [N- (4-Bromo-benzyl) -N-methylaminomethyl] aniline
• 87. 4- [N- (4-Fluoro-benzyl) -N-methylaminomethyl] aniline
• 88. 4- [N- (4-Methylbenzyl) -N-methylaminomethyl] aniline
• 89. 4- [N- (4-nitro-phenethyl) -N-methylaminomethyl] aniline
• 90. 4- (N-phenethyl-N-benzylaminomethyl) aniline
• 91. 4- (N-phenethyl-N-cyclohexylaminomethyl) aniline  
• 92. 4- [N- (2- (pyridin-2-yl) ethyl) -N-methylaminomethyl] - aniline
• 93. 4- [N- (2- (pyridin-4-yl) ethyl) -N-methylaminomethyl] - aniline
• 94. 4- [N- (pyridin-4-ylmethyl) -N-methylaminomethyl] aniline
• 95. 4- (N, N-dibenzylaminomethyl) aniline
• 96. 4- [N- (4-Nitro-benzyl) -N-propyl-aminomethyl] aniline
• 97. 4- [N-Benzyl-N- (3-cyano-propyl) aminomethyl] aniline
• 98. 4- (N-Benzyl-N-allyl aminomethyl) aniline
• 99. 4- [N-Benzyl-N- (2,2,2-trifluoroethyl) aminomethyl] aniline
• 100.4 - [(Benzo (1,3) dioxol-5-ylmethyl) methylaminomethyl] - aniline
• 101. 4- (7-chloro-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl- methyl) aniline
• 102. 4- (7,8-dichloro-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl- methyl) aniline
• 103. 4- (7-methoxy-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl- methyl) aniline
• 104. 4- (7-methyl-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl- methyl) aniline
• 105. 4- (7,8-Dimethoxy-2,3,4,5-tetrahydro-benzo (d) azepin-3-yl- methyl) aniline  
• 106. 4- (6,7-dichloro-1,2,3,4-tetrahydro-isoquinolin-2-yl- methyl) aniline
• 107. 4- (6,7-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-2-yl- methyl) aniline
• 108. 4- (6-chloro-1,2,3,4-tetrahydro-isoquinolin-2-yl-methyl) - aniline
• 109. 4- (7-chloro-1,2,3,4-tetrahydro-isoquinolin-2-yl - methyl) - aniline
• 110. 4- (6-methoxy-1,2,3,4-tetrahydro-isoquinolin-2-yl- methyl) aniline
• 111. 4- (7-methoxy-1,2,3,4-tetrahydro-isoquinolin-2-yl- methyl) aniline
• 112. 4- (2,3,4,5-tetrahydro-azepino (4,5-b) pyrazin-3-yl- methyl) aniline
• 113. 4- (7-Amino-2,3,4,5-tetrahydro-azepino (4,5-b) pyrazine-3- yl-methyl) aniline
• 114. 4- (2-Amino-5,6,7,8-tetrahydro-azepino (4,5-d) thiazole-6- yl-methyl) aniline
• 115. 4- (5,6,7,8-tetrahydro-azepino (4,5-d) thiazol-6-yl- methyl) aniline
• 116. 4- (4-methyl-piperazin-1-yl) aniline
• 117. 4- [N- (2-Dimethylaminoethyl) -N-methylamino] aniline
• 118. 4- [N- (3-Dimethylamino-propyl) -N-methylamino] aniline  
• 119. N- (3-Dimethylamino-propyl) -N-methylsulfonyl-p- phenylenediamine
• 120.4 - [(N-dimethylaminocarbonylmethyl-N-methylsulfonyl) - amino] aniline
• 121. N- (4-aminophenyl) -N-methyl-methanesulfonamide
• 122. 4- (imidazol-4-yl) aniline
• 123. 4- (tetrazol-5-yl) aniline
• 124. 4- [N- (2-Dimethylaminoethyl) -N-propionylamino] aniline
• 125. N- (Dimethylaminomethylcarbonyl) -N-methyl-p- phenylenediamine
• 126. N - [(2-dimethylaminoethyl) carbonyl] -N-methyl-p- phenylenediamine
• 127. 4- (N-Acetyl-N-dimethylaminocarbonylmethyl) amino) aniline
• 128. N-methylaminocarbonylmethyl-N-methylsulfonyl-p- phenylenediamine
• 129. N-aminocarbonylmethyl-N-methylsulfonyl-p-phenylenediamine
• 130. 4- (imidazolidin-2,4-dione-5-ylidenemethyl) aniline
• 131. 4- (Imidazolidin-2,4-dione-5-ylmethyl) aniline
• 132. 4- (2-oxopyrrolidin-1-ylmethyl) aniline
• 133. N-cyanomethyl-N-methylsulfonyl-p-phenylenediamine
• 134. 4- [2- (imidazol-4-yl) ethyl] aniline  
• 135. 4 - [(4-Methylpiperazin-1-yl) methyl] aniline
• 136. 4- [N- (2- (N-Benzyl-N-methylamino) ethyl) -N-me thylsulfonylamino] aniline
• 137. 4- [N- (3- (N-Benzyl-N-methylamino) propyl) -N-me thylsulfonylamino] aniline
• 138. N-Cyclohexyl-p-phenylenediamine
• 139. 4- (pyridin-4-ylmethyl) aniline
• 140. 4- (imidazol-1-ylmethyl) aniline
• 141. 4-benzyl aniline
• 142. N- (3-trifluoroacetylamino-propyl) -N-methylsulfonyl-p- phenylenediamine
• 143. tert-butyl 4-aminophenylacetate
• 144. 4- (imidazol-2-yl) aniline
• 145. 4- (1-methylimidazol-2-yl) aniline
• 146. 4- (1-ethyl-imidazol-2-yl) aniline
• 147. 4- (1-benzylimidazol-2-yl) aniline
• 148. 4- [N- (2-Dimethylamino-ethyl) -N-methylsulfonylamino] -3- amino aniline
• 149. 4- [N- (2-Dimethylamino-ethyl) -N-methylsulfonylamino] -3- chloro-aniline
• 150. 4- [N- (2-Dimethylaminoethyl) -N-acetylamino] -3-amino aniline  
• 151. 4- [N- (2-Dimethylaminoethyl) -N-acetylamino] -3-bromo aniline
• 152. 4- [2- (4-Hydroxy-piperidin-i-yl) ethyl amino] aniline
• 153. N- (2-Dimethylamino-ethyl) -N-ethylsulfonyl-p- phenylenediamine
• 154. N- (2-Dimethylamino-ethyl) -N-propylsulfonyl-p- phenylenediamine
• 155. N- (2-Dimethylamino-ethyl) -N-isopropylsulfonyl-p- phenylenediamine
• 156. N- (2-Dimethylamino-ethyl) -N-butylsulfonyl-p- phenylenediamine
• 157. N- (2-Dimethylamino-ethyl) -N-benzylsulfonyl-p- phenylenediamine
• 158. N- (2-Dimethylamino-ethyl) -N-phenylsulfonyl-p- phenylenediamine
• 159. 4 - ((3-Hydroxy-pyrrolidin-1-yl) methyl) aniline
• 160. 4- [N- (2-Dimethylamino-ethyl) -N- (furan-2-carbonyl) - amino] aniline
• 161. 4- [N- (2-Dimethylamino-ethyl) -N- (2-methoxy-benzoyl) - amino] aniline
• 162. 4- [N- (2-Dimethylamino-ethyl) -N- (pyridine-3-carbonyl) - amino] aniline
• 163. 4- [N- (2-Dimethylamino-ethyl) -N- (phenyl-acetyl) -amino] - aniline  
• 164. N- (piperidin-1-yl-methylcarbonyl) -N-methyl-p- phenylenediamine
• 165. N- (morpholin-4-yl-methylcarbonyl) -N-methyl-p- phenylenediamine
• 166. N - [(4-benzylpiperazin-1-yl) methylcarbonyl] -N-methyl-p- phenylenediamine
• 167. N- (pyrrolidin-1-yl-methylcarbonyl) -N-methyl-p- phenylenediamine
• 168. 4- (5-methylimidazol-4-yl) aniline
• 169. N - [(2-dimethylaminoethyl) carbonyl] -N-isopropyl-p- phenylenediamine
• 170. N - [(2-dimethylaminoethyl) carbonyl] -N-benzyl-p- phenylenediamine
• 171. N- (N-aminocarbonylmethyl-N-methylamino) - methylcarbonyl) -N-methyl-p-phenylenediamine
• 172. N - [(N-benzyl-N-methylamino) methylcarbonyl] -N-methyl-p- phenylenediamine
• 173. N- [Di- (2-methoxyethyl) amino-methylcarbonyl] -N-methyl-p- phenylenediamine
• 174. N - [(2- (4-tert-butoxycarbonyl-piperazin-1-yl) ethyl) - carbonyl] -N-methyl-p-phenylenediamine
• 175. N - [(2- (piperidin-1-yl) ethyl) carbonyl] -N-methyl-p- phenylenediamine  
• 176. N - [(2- (N-benzyl-N-methylamino) ethyl) carbonyl] -N- methyl-p-phenylenediamine
• 177. N- (Dimethylaminomethylcarbonyl) -N-isopropyl-p- phenylenediamine
• 178. N- (piperidin-1-yl-methylcarbonyl) -N-isopropyl-p- phenylenediamine
• 179. N - [(4-tert-butoxycarbonyl-piperazin-1-yl) - methylcarbonyl] -N-isopropyl-p-phenylenediamine
• 180. N - [(N-benzyl-N-methylamino) methylcarbonyl] -N-benzyl-p- phenylenediamine
• 181. N- (Dimethylaminomethylcarbonyl) -N-benzyl-p- phenylenediamine
• 182. N- (piperidin-1-yl-methylcarbonyl) -N-benzyl-p- phenylenediamine
• 183. 4- (1,2,4-Triazol-1-ylmethyl) aniline
• 184. 4- (1,2,3-Triazol-2-ylmethyl) aniline
• 185. 4- (1,2,3-Triazol-1-ylmethyl) aniline
• 186.4 - [(N-ethoxycarbonylmethyl-N-methylamino) methyl] - aniline
• 187. 4 - [(N-aminocarbonylmethyl-N-methylamino) methyl] aniline
• 188. 4- (Azetidin-1-ylmethyl) aniline
• 189. 4 - [(Di- (2-methoxy-ethyl) amino) methyl] aniline  
• 190.4 - [(N- (2- (2-methoxyethoxy) ethyl) -N-methylamino) - methyl] aniline
• 191. 4- [N- (N-tert-Butoxycarbonyl-3-aminopropyl) -N-methyl aminomethyl] aniline
• 192.4 - [(N- (Methylcarbamoyl-methyl) -N-methyl-amino) -methyl] - aniline
• 193. 4 - [(N- (Dimethylcarbamoyl-methyl) -N-methyl-amino) - methyl] aniline
• 194. 4 - [(N-Propyl-N-methylamino) methyl] aniline
• 195.4 - [(N- (2-Dimethylaminoethyl) -N-methylamino) methyl] - aniline
• 196. 4 - [(N- (3-Dimethylamino-propyl) -N-methylamino) methyl] - aniline
• 197. 4 - [(N- (2-methoxyethyl) -N-methylamino) methyl] aniline
• 198.4 - [(N- (2-Hydroxyethyl) -N-methylamino) methyl aniline
• 199.4 - [(N- (Dioxolan-2-ylmethyl) -N-methylamino) methyl] - aniline
• 200. 4- (3-oxopiperazin-1-ylmethyl) aniline
• 201. N- [Di- (2-hydroxyethyl) amino-methylcarbonyl] -N-methyl-p- phenylenediamine
• 202. N - [(N- (2-methoxyethyl) -N-methylamino) methylcarbonyl] - N-methyl-p-phenylenediamine
• 203. N - [(N- (2-Dimethylamino-ethyl) -N-methyl-amino) - methylcarbonyl] -N-methyl-p-phenylenediamine  
• 204. N - [(4-methyl-piperazin-1-yl) methylcarbonyl] -N-methyl-p- phenylenediamine
• 205. N - [(imidazol-1-yl) methylcarbonyl] -N-methyl-p- phenylenediamine
• 206. N - [(Phthalimido-2-yl) methylcarbonyl] -N-methyl-p- phenylenediamine

Example XXI 4- (4-hydroxymethylpiperidin-1-ylmethylamino) aniline

1.1 g of 4- (4-ethoxycarbonyl-piperidin-1-yl-methylamino) aniline are suspended in 15 ml of tetrahydrofuran. At room temperature, 175 mg of lithium borohydride are added, the mixture is stirred for 24 h, another 175 mg of lithium borohydride are added and, after a further 7.5 hours, 15 ml of water are added and the mixture is stirred for 10 minutes. It is extracted three times with 15 mL ethyl acetate each. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulfate and evaporated. The residue is purified on a silica gel column using methylene chloride / methanol / ammonia 4: 1: 0.01 as the eluent.
Yield: 200 mg (27% of theory)
R _f value: 0.4 (silica gel, methylene chloride / methanol / ammonia 4: 1: 0.01)
Melting point: 157 ° C

Example XXII 4-Methoxycarbonylmethyl-3-nitro-benzoic acid methyl ester

54.3 g of 3-nitro-benzoic acid methyl ester and 29.0 g of chloroacetic acid methyl ester are dissolved in 100 ml of dimethylformamide and this solution is added dropwise at -10 ° C. to a solution of 78.5 g of potassium tert-butoxide in 500 ml of dimethylformamide. The mixture is stirred for a further 10 minutes at room temperature and, after this time, the solution is poured onto 350 ml of concentrated hydrochloric acid in 2 l of ice water. The solution is stirred for 0.5 hours, the precipitate obtained is suction filtered and washed with water. The product is recrystallized from 150 ml of methanol and dried in vacuo at 40 ° C.
Yield: 48.3 g (51% of theory), contains about 20% methyl 6-methoxycarbonylmethyl-3-nitro-benzoate
R _f value: 0.7 (silica gel, petroleum ether / ethyl acetate = 1: 1)
Melting point: 65-73 ° C

The following compound is produced analogously to Example XXII:

• 1. 4-Methoxycarbonylmethyl-3-nitro-benzoic acid ethyl ester
  Made from 4-thoxycarbonylmethyl-3-nitro-benzoic acid ethyl ester

Example XXIII 2-Indolinone-6-carboxylic acid methyl ester

48.3 g of 4-methoxycarbonylmethyl-3-nitro-benzoic acid methyl ester are dissolved in 800 ml of concentrated acetic acid, 5.0 g of palladium on carbon (10 percent) are added and the solution is hydrogenated for 2.5 hours at room temperature and 50 psi. The catalyst is filtered off and the filtrate is evaporated. The residue is taken up in 150 ml of tert-butyl methyl ether, filtered again and dried in vacuo at 100 ° C.
Yield: 28.6 g (98% of theory),
R _f value: 0.4 (silica gel, methylene chloride / methanol = 10: 1)
Melting point: 208-211 ° C

The following compound is prepared analogously to Example XXIII:

• 1. Ethyl 2-indolinone-6-carboxylate
  Made from 4-methoxycarbonylmethyl-3-nitro-benzoic acid ethyl ester

Example XXIV 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-ethoxycarbonyl-2-in dolinon

15.0 g of ethyl 2-indolinone-6-carboxylate, 49.6 ml of triethyl ortho benzoate and 150 ml of acetic anhydride are stirred at 110 ° C. for 4 hours. After this time, the solvent is stripped off, the residue is recrystallized from petroleum ether and dried in vacuo at 50.degree.
Yield: 16.9 g (61% of theory),
R _f value: 0.5 (silica gel, petroleum ether / methylene chloride / vinegar ester = 5: 4: 1)
Melting point: 98-100 ° C
C ₂₂ H ₂₁ NO ₅

The following compounds are prepared analogously to Example XXIV:

• 1. 1-Acetyl-3- (1-ethoxy-1-phenylmethylene) -6-methoxycarbonyl-2-indolinone
  Made from 2-indolinone-6-carboxylic acid methyl ester, ortho benzoic acid triethyl ester and acetic anhydride
• 2. 1-Acetyl-3- (1-ethoxy-1-ethylmethylene) -6-ethoxycarbonyl-2-indolinone
  Made from 2-indolinone-6-carboxylic acid ethyl ester, ortho propionic acid triethyl ester and acetic anhydride

Making the end connections example 1 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone trifluoroacetate

300 mg of resin obtained according to Example II are suspended in 3 ml of dimethylformamide and shaken with 0.2 g of 4- (piperidin-1-ylmethyl) aniline at 70 ° C. for 22 hours. It is then filtered off and the resin is washed several times with methylene chloride, methanol and dimethylformamide. Then 1 ml of methanolic ammonia is added for 2 hours to remove the acetyl group. Then, after further washing, 4 ml of 10% trifluoroacetic acid in methylene chloride are added over 60 minutes, the resin is separated off and the solution is concentrated.
Yield: 69 mg
R _f value: 0.1 (silica gel, methylene chloride / methanol = 9: 1)
C ₂₈ H ₂₈ N ₄ O ₂
Mass spectrum: m / z = 452 (M ⁺ )

The following compounds are prepared analogously to Example 1:

• 1. 3-Z- (1-anilino-1-phenylmethylene) -6-carbamoyl-2-indolinone
  Made from the resin and aniline obtained in Example II
  C ₂₂ H ₁₇ N ₃ O ₂
  Mass spectrum: m / z = 355 (M ⁺ )
• 2. 3-Z- [1- (4-Dimethylaminomethyl-anilino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 4-dimethylaminomethyl-aniline
  C ₂₅ H ₂₄ N ₄ O ₂
  Mass spectrum: m / z = 412 (M ⁺ )
• 3. 3-Z- [1- (4- (2-Diethylaminoethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 4- (2-diethylamino-ethyl) aniline
  C ₂₈ H ₃₀ N ₄ O ₂
  Mass spectrum: m / z = 454 (M ⁺ )
• 4. 3-Z- [1- (4- (morpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 4- (morpholin-4-yl-methyl) aniline
  R _f value: 0.50 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₇ H ₂₆ N ₄ O ₃
  Mass spectrum: m / z = 454 (M ⁺ )
• 5. 3-Z- [1- (4- (1-Oxo-thiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 4- (1-oxothiomorpholin-4-ylmethyl) aniline
  R _f value: 0.30 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₇ H ₂₆ N ₄ O ₃ S
  Mass spectrum: m / z = 486 (M ⁺ )
• 6. 3-Z- [1- (4- (1,1-Dioxothiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Prepared from the resin obtained according to Example II and 4- (1,1-dioxo-thiomorpholin-4-yl-methyl) aniline
  R _f value: 0.30 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₇ H ₂₆ N ₄ O ₄ S
  Mass spectrum: m / z = 502 (M ⁺ )
• 7. 3-Z- [1- (4- (Benzylaminomethyl) anilino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone trifluoroacetate
  Prepared from the resin obtained according to Example II and 4- [N- (phenyl-methyl) -N-tert.butoxycarbonyl-aminomethyl] aniline
  R _f value: 0.40 (silica gel, methylene chloride / methanol = 4: 1)
  C ₃₀ H ₂₆ N ₄ O ₂
  Mass spectrum: m / z = 474 (M ⁺ )
• 8. 3-Z- [1- (4- (aminomethyl) anilino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 4- (N-tert-butoxycarbonylaminomethyl) aniline
  R _f value: 0.10 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₃ H ₂₀ N ₄ O ₂
  Mass spectrum: m / z = 384 (M ⁺ )
• 9. 3-Z- [1- (4- (2,6-Dimethylpiperidin-1-ylmethyl) anilino) - 1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Prepared from the resin obtained according to Example II and 4- (2,6-dimethylpiperidin-1-yl-methyl) aniline
  R _f value: 0.45 (silica gel, methylene chloride / methanol = 4: 1)
  C ₃₀ H ₃₂ N ₄ O ₂
  Mass spectrum: m / z = 480 (M ⁺ )
• 10. 3-Z- [1- (4- (pyrrolidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 4- (pyrrolidin-1-yl-methyl) aniline
  R _f value: 0.15 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₇ H ₂₆ N ₄ O ₂
  Mass spectrum: m / z = 438 (M ⁺ )
• 11. 3-Z- [1- (3- (Dimethylaminomethyl) anilino) -1-phenylmethylene len -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 3-dimethylaminomethyl-aniline
  R _f value: 0.23 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₅ H ₂₄ N ₄ O ₂
  Mass spectrum: m / z = 412 (M ⁺ )
• 12. 3-Z- [1- (3- (N-Methyl-N-ethylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 3- (N-methyl-N-ethyl-aminomethyl) aniline
  R _f value: 0.23 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₆ H ₂₆ N ₄ O ₂
  Mass spectrum: m / z = 426 (M ⁺ )
• 13. 3-Z- [1- (3- (methylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained according to Example II and 4- (N-tert.butoxycarbonyl-N-methyl-aminomethyl) aniline
  R _f value: 0.06 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₄ H ₂₂ N ₄ O ₂
  Mass spectrum: m / z = 399 (M + H ⁺ )
• 14. 3-Z- [1- (3-hydroxymethylanilino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II and 3-aminobenzyl alcohol
  R _f value: 0.7 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₃ H ₁₉ N ₃ O ₃
  Mass spectrum: m / z = 385 (M ⁺ )
• 15. 3-Z- [1- (4- (methoxycarbonylmethylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Prepared from the resin obtained according to Example II and 4- (N-methoxycarbonylmethyl-N-tert.butoxycarbonyl-aminomethyl) aniline
  R _f value: 0.40 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₆ H ₂₄ N ₄ O ₄
  Mass spectrum: m / z = 457 (M + H ⁺ )
• 16. 3-Z- [1- (4- (N-methylsulfonyl-N- (dimethylaminocarbonylmethyl) amino) anilino) -1-phenylmethylene] -6-carbamoyl-2-dolinone
  Made from the resin obtained in Example II and 4- (N-methylsulfonyl-N- (dimethylaminocarbonylmethyl) amino) aniline
  R _f value: 0.40 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₇ H ₂₇ N ₅ O ₅ S
  Mass spectrum: m / z = 533 (M ⁺ )
• 17. 3-Z- [1- (4- (N-acetylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II and 4- (N-acetylaminomethyl) aniline
  R _f value: 0.70 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₅ H ₂₂ N ₄ O ₃
  Mass spectrum: m / z = 426 (M ⁺ )
• 18. 3-Z- [1- (3,4-Dimethoxy-anilino) -1-phenylmethylene] -6-carb amoyl-2-indolinone
  Made from the resin obtained in Example II and 3, 4-dimethoxy-aniline
  R _f value: 0.40 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₄ H ₂₁ N ₃ O ₄
  Mass spectrum: m / z = 415 (M ⁺ )
• 19. 3-Z- [1- (4- (morpholin-4-yl) anilino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 4-morpholin-4-yl-aniline
  R _f value: 0.20 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₆ H ₂₄ N ₄ O ₃
  Mass spectrum: m / z = 440 (M ⁺ )
• 20. 3-Z- [1- (4-acetylamino-anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II and 4-acetylamino-aniline
  R _f value: 0.25 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₄ H ₂₀ N ₄ O ₃
  Mass spectrum: m / z = 412 (M ⁺ )
• 21. 3-Z- [1- (4-amino-anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II and 4-amino-aniline
  R _f value: 0.40 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₂ H ₁₈ N ₄ O ₂
  Mass spectrum: m / z = 370 (M ⁺ )
• 22. 3-Z- [1- (4-N-methyl-N-acetylamino anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II and 4- (N-methyl-N-acetylamino) aniline
  C ₂₅ H ₂₂ N ₄ O ₃
  Mass spectrum: m / z = 426 (M ⁺ )
• 23. 3-Z- [1- (4-ethoxycarbonylanilino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone
  Prepared from the resin obtained according to Example II and 4-amino-benzoic acid ethyl ester
  C ₂₅ H ₂₁ N ₃ O ₄
  Mass spectrum: m / z = 427 (M ⁺ )
• 24. 3-Z- [1- (4-carboxy-anilino) -1-phenylmethylene] -6-carb amoyl-2-indolinone
  Made from the resin obtained in Example II and 4-amino-benzoic acid
  R _f value: 0.11 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₃ H ₁₇ N ₃ O ₄
  Mass spectrum: m / z = 398 (M - H ⁺ )
• 25. 3-Z- [1- (4-Benzylcarbamoyl-anilino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II and 4-amino-benzoic acid-benzylamide
  R _f value: 0.21 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₀ H ₂₄ N ₄ O ₂
  Mass spectrum: m / z = 488 (M ⁺ )
• 26. 3-Z- [1- (cyclohexylamino) -1-phenylmethylene] -6-carbamoyl-2-indolinone
  Made from the resin and cyclohexylamine obtained in Example II
  R _f value: 0.60 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₂ H ₂₃ N ₃ O ₂
  Mass spectrum: m / z = 361 (M ⁺ )
• 27. 3-Z- [1- (4-Amino-cyclohexylamino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 4-amino-cyclohexylamine
  C ₂₂ H ₂₄ N ₄ O ₂
  Mass spectrum: m / z = 376 (M ⁺ )
• 28. 3-Z- [1- (N-methylpiperidin-4-ylamino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 4-amino-1-methyl-piperidine
  R _f value: 0.15 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₂ H ₂₄ N ₄ O ₂
  Mass spectrum: m / z = 376 (M ⁺ )
• 29. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Prepared from the resin obtained in Example II (2) and 4- (piperidin-1-yl-methyl) aniline
  R _f value: 0.30 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₃ H ₂₆ N ₄ O ₂
  Mass spectrum: m / z = 390 (M ⁺ )
• 30. 3-Z- [1- (3-dimethylaminomethyl-anilino) -1-methyl-methylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II (2) and 3-dimethylaminomethyl-aniline
  R _f value: 0.51 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₀ H ₂₂ N ₄ O ₂
  Mass spectrum: m / z = 351 (M + H ⁺ )
• 31. 3-Z- [1- (4- (N-methyl-N-benzylaminomethyl) anilino) -1-methyl-methylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Prepared from the resin obtained in Example II (2) and 4- (N-methyl-N-benzylaminomethyl) aniline
  R _f value: 0.73 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₆ H ₂₆ N ₄ O ₂
  Mass spectrum: m / z = 426 (M ⁺ )
• 32. 3-Z- [1- (4- (N-methylsulfonyl-N- (2-dimethylaminoethyl) amino) anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Prepared from the resin obtained in Example II (2) and 4- (N-methylsulfonyl-N- (2-dimethylamino-ethyl) -amino) aniline
  C ₂₂ H ₂₇ N ₅ O ₄ S
  Mass spectrum: m / z = 458 (M + H ⁺ )
• 33. 3-Z- [1- (4-chloroanilino) -1-methylmethylene] -6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II (2) and 4-chloro-aniline
  R _f value: 0.10 (silica gel, methylene chloride / methanol = 9: 1)
  C ₁₇ H ₁₄ ClN ₃ O ₂
  Mass spectrum: m / z = 327/329 (M ⁺ )
• 34. 3-Z- [1- (3-chloro-anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II (2) and 3-chloro-aniline
  R _f value: 0.11 (silica gel, methylene chloride / methanol = 9: 1)
  C ₁₇ H ₁₄ ClN ₃ O ₂
  Mass spectrum: m / z = 327/329 (M ⁺ )
• 35. 3-Z- [1- (4-methoxycarbonylanilino) -1-methylmethylene] - 6-carbamoyl-2-indolinone
  Prepared from the resin obtained according to Example II (2) and 4-amino-benzoic acid methyl ester
  R _f value: 0.11 (silica gel, methylene chloride / methanol = 9: 1)
  C ₁₉ H ₁₇ N ₃ O ₄
  Mass spectrum: m / z = 351 (M ⁺ )
• 36. 3-Z- [1- (4-carboxy-anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II (2) and 4-amino-benzoic acid
  C ₁₈ H ₁₅ N ₃ O ₄
  Mass spectrum: m / z = 336 (M - H ⁺ )
• 37. 3-Z- [1- (4-methyl-3-nitro-anilino) -1-methylmethylene] - 6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II (2) and 4-methyl-3-nitro-aniline
  R _f value: 0.82 (silica gel, methylene chloride / methanol = 4: 1)
  C ₁₈ H ₁₆ N ₄ O ₄
  Mass spectrum: m / z = 352 (M ⁺ )
• 38. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-propylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Prepared from the resin obtained according to Example II (4) and 4- (piperidin-1-yl-methyl) aniline
  R _f value: 0.37 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₅ H ₃₀ N ₄ O ₂
  Mass spectrum: m / z = 418 (M ⁺ )
• 39. 3-Z- [1- (3-dimethylaminomethyl-anilino) -1-propyl-methylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II (4) and 3-dimethylaminomethyl-aniline
  R _f value: 0.42 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₂ H ₂₆ N ₄ O ₂
  Mass spectrum: m / z = 378 (M ⁺ )
• 40. 3-Z- [1- (4- (N-methyl-N-benzylaminomethyl) anilino) -1-pro pylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II (4) and 4- (N-methyl-N-benzylaminomethyl) aniline
  R _f value: 0.81 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₈ H ₃₀ N ₄ O ₂
  Mass spectrum: m / z = 454 (M ⁺ )
• 41. 3-Z- [1- (4- (N-Methylsulfonyl-N- (2-dimethylaminoethyl) amino) anilino) -1-propylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Prepared from the resin obtained according to Example II (4) and 4- (N-methylsulfonyl-N- (2-dimethylamino-ethyl) amino) aniline
  R _f value: 0.59 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₄ H ₃₁ N ₅ O ₄ S
  Mass spectrum: m / z = 486 (M + H ⁺ )
• 42. 3-Z- [1- (4-chloroanilino) -1-propylmethylene] -6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II (4) and 4-chloro-aniline
  R _f value: 0.17 (silica gel, methylene chloride / methanol = 9: 1)
  C ₁₉ H ₁₈ ClN ₃ O ₂
  Mass spectrum: m / z = 355/357 (M ⁺ )
• 43. 3-Z- [1- (3-chloroanilino) -1-propylmethylene] -6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II (4) and 3-chloro-aniline
  R _f value: 0.12 (silica gel, methylene chloride / methanol = 9: 1)
  C ₁₉ H ₁₈ ClN ₃ O ₂
  Mass spectrum: m / z = 355/357 (M ⁺ )
• 44. 3-Z- [1- (4-methoxycarbonylanilino) -1-propylmethylene] - 6-carbamoyl-2-indolinone
  Prepared from the resin obtained according to Example II (4) and 4-amino-benzoic acid methyl ester
  R _f value: 0.8 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₁ H ₂₁ N ₃ O ₄
  Mass spectrum: m / z = 379 (M ⁺ )
• 45. 3-Z- [1- (4-carboxy-anilino) -1-propylmethylene] -6-carbamoyl-2-indolinone
  Made from the resin and 4-amino-benzoic acid obtained in Example II (4)
  C ₂₀ H ₁₉ N ₂ O ₄
  Mass spectrum: m / z = 364 (M - H ⁺ )
• 46. 3-Z- [1- (4-methyl-3-nitro-anilino) -1-propylmethylene] - 6-carbamoyl-2-indolinone
  Made from the resin obtained in Example II (4) and 4-methyl-3-nitro-aniline
  R _f value: 0.86 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₀ H ₂₀ N ₄ O ₄
  Mass spectrum: m / z = 380 (M ⁺ )

Example 2 3-Z- [1- (3- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] - 6-carbamoyl-2-indolino-trifluoroacetate

2.0 g of resin obtained according to Example II are reacted analogously to Example 1 with 2.0 g of 3-aminobenzyl alcohol in 20 ml of dimethylformamide at 70 ° C. for 22 hours. Then the solvent is suctioned off and the resin is washed several times with dimethylformamide and methylene chloride. 200 mg of the moist loaded resin are then suspended in 2 ml of methylene chloride and left to stand for 2 hours at room temperature with 0.2 ml of methanesulfonic acid chloride and 0.1 ml of triethylamine. The resin is then washed several times with methylene chloride, suspended in 2 ml of methylene chloride and mixed with 0.2 ml of piperidine. After 1 hour the resin is washed with methylene chloride and dimethyl formamide and then treated analogously to Example 1 with trifluoroacetic acid.
Yield: 15 mg
R _f value: 0.30 (silica gel, methylene chloride / methanol = 4: 1)
C ₂₈ H ₂₈ N ₄ O ₂
Mass spectrum: m / z = 452 (M ⁺ )

The following compounds are prepared analogously to Example 2:

• 1. 3-Z- [1- (3- (diethylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin and diethylamine obtained in Example II
  R _f value: 0.80 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₇ H ₂₈ N ₄ O ₂
  Mass spectrum: m / z = 440 (M ⁺ )
• 2. 3-Z- [1- (3- (benzylaminomethyl) anilino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin and benzylamine obtained in Example II
  R _f value: 0.80 (silica gel, methylene chloride / methanol = 4: 1)
  C ₃₀ H ₂₆ N ₄ O ₂
  Mass spectrum: m / z = 474 (M ⁺ )
• 3. 3-Z- [1- (3- (N-methyl-N-benzylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and N-methyl-benzylamine
  R _f value: 0.80 (silica gel, methylene chloride / methanol = 4: 1)
  C ₃₁ H ₂₈ N ₄ O ₂
  Mass spectrum: m / z = 488 (M ⁺ )
• 4. 3-Z- [1- (3- (butylaminomethyl) anilino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin and butylamine obtained in Example II
  R _f value: 0.40 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₇ H ₂₈ N ₄ O ₂
  Mass spectrum: m / z = 440 (M ⁺ )
• 5. 3-Z- [1- (3- (aminomethyl) anilino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin and ammonia obtained in Example II
  C ₂₃ H ₂₀ N ₄ O ₂
  Mass spectrum: m / z = 385 (M + H ⁺ )
• 6. 3-Z- [1- (3- (N- (3-Dimethylaminopropyl) -N-methylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 1-dimethylamino-3-methylaminopropane
  R _f value: 0.67 (silica gel, methylene chloride / methanol 4: 1)
  C ₂₉ H ₃₃ N ₅ O ₂
  Mass spectrum: m / z = 484 (M + H ⁺ )
• 7. 3-Z- [1- (3- (N- (2-Dimethylaminoethyl) -N-methylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone trifluoroacetate
  Made from the resin obtained in Example II and 1-dimethylamino-2-methylaminoethane
  R _f value: 0.40 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₈ H ₃₁ N ₅ O ₂
  Mass spectrum: m / z 470 (M + H ⁺ )

Example 3 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone

1.5 g of 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone and 1.1 g of 4- (piperidin-1-ylmethyl) aniline are dissolved in 15 ml of dimethylformamide and 45 minutes stirred at 100 ° C. After cooling, 5.0 ml of piperidine are added and the mixture is stirred for a further 3 hours at room temperature. The solvent is removed and the residue is purified on an alumina column (activity: 2-3) with methylene chloride / ethanol (100: 3) as the eluent.
Yield: 1.1 g (58% of theory),
R _f value: 0.5 (aluminum oxide, methylene chloride / ethanol = 100: 3)
C ₃₀ H ₃₁ N ₃ O ₃
Mass spectrum: m / z = 481 [M ⁺ ]

The following compounds are prepared analogously to Example 3:

• 1. 3-Z- [1- (4-bromoanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4-bromoaniline
  R _f value: 0.4 (silica gel, toluene / ethyl acetate = 5: 1)
  C ₂₄ H ₁₉ BrN ₂ O ₃
  Mass spectrum: m / z = 462/464 [M ⁺ ]
• 2. 3-Z- [1- (3- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 3- (dimethylaminomethyl) aniline
  R _f value: 0.5 (aluminum oxide, methylene chloride / ethanol = 30: 1)
  C ₂₇ H ₂₇ N ₃ O ₃
  ESI mass spectrum: m / z = 442 [M + H ⁺ ]
• 3. 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (dimethylaminomethyl) aniline
  R _f value: 0.7 (aluminum oxide, ethyl acetate / ethanol = 20: 1)
  C ₂₇ H ₂₇ N ₃ O ₃
  ESI mass spectrum: m / z = 442 [M + H ⁺ ]
• 4. 3-Z- [1- (4 - [(2,6-dimethylpiperidin-1-yl) methyl] anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4 - [(2,6-dimethylpiperidin-1-yl) methyl] aniline
  R _f value: 0.6 (silica gel, methylene chloride / ethanol = 5: 1)
  C ₃₂ H ₃₅ N ₃ O ₃
  Mass spectrum: m / z = 509 [M ⁺ ]
• 5. 3-Z- [1- (4- (2-Dimethylaminoethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (2-dimethylamino-ethyl) aniline
  R _f value: 0.2 (silica gel, methylene chloride / ethanol = 5: 1)
  C ₂₈ H ₂₉ N ₃ O ₃
  Mass spectrum: m / z = 455 [M ⁺ ]
• 6. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-acetylamino) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylaminoethyl) - N-acetylamino) aniline
  R _f value: 0.4 (aluminum oxide, methylene chloride / ethanol = 20: 1)
  C ₃₀ H ₃₂ N ₄ O ₄
  Mass spectrum: m / z = 512 [M ⁺ ]
• 7. 3-Z- [1- (4-tert-Butyloxycarbonyl-anilino) -1-phenylmethylene) -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4-tert-butyloxycarbonyl-aniline
  R _f value: 0.4 (aluminum oxide, methylene chloride / ethanol = 40: 1)
  C ₂₉ H ₂₈ N ₂ O ₅
  Mass spectrum: m / z = 484 [M ⁺ ]
• 8. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) alanino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (N- (3-dimethylamino-propyl) -N-acetylamino) aniline
  R _f value: 0.2 (aluminum oxide, methylene chloride / ethanol = 40: 1)
  C ₃₁ H ₃₄ N ₄ O ₄
  Mass spectrum: m / z = 526 [M ⁺ ]
• 9. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonylamino) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and N- (2-dimethylamino-ethyl) -N-methylsulfonyl-p-phenylenediamine
  R _f value: 0.3 (aluminum oxide, methylene chloride / ethanol = 40: 1)
  C ₂₉ H ₃₂ N ₄ O ₅ S
  Mass spectrum: m / z = 548 [M ⁺ ]
• 10. 3-Z- [1- (4- (4-methyl-piperazin-1-yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (4-methyl-piperazin-1-yl) aniline
  R _f value: 0.3 (aluminum oxide, ethyl acetate)
  C ₂₉ H ₃₀ N ₄ O ₃
  ESI mass spectrum: m / z = 483 [M + H ⁺ ]
• 11. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylamino) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylaminoethyl) - N-methylamino) aniline
  R _f value: 0.5 (aluminum oxide, methylene chloride / ethanol = 20: 1)
  C ₂₉ H ₃₂ N ₄ O ₃
  ESI mass spectrum: m / z = 485 [M + H ⁺ ]
• 12. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (N- (3-dimethylamino-propyl) -N-methylamino) aniline
  R _f value: 0.5 (aluminum oxide, ethyl acetate)
  C ₃₀ H ₃₄ N ₄ O ₃
  ESI mass spectrum: m / z = 499 [M + H ⁺ ]
• 13. 3-Z- [1- (4- (N-methyl-acetylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4-amino-N-methyl-acetanilide
  R _f value: 0.3 (silica gel, methylene chloride / ethanol = 15: 1)
  C ₂₇ H ₂₅ N ₃ O ₄
  Mass spectrum: m / z = 455 [M ⁺ ]
• 14. 3-Z- [1- (4- (N-methyl-methylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and N- (4-aminophenyl) -N-methyl methanesulfonamide
  R _f value: 0.8 (aluminum oxide, ethyl acetate)
  C ₂₆ H ₂₅ N ₃ O ₅ S
  Mass spectrum: m / z = 491 [M ⁺ ]
• 15. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indoli non
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and N- (3-dimethylamino-propyl) -N-methylsulfonyl-p-phenylenediamine
  R _f value: 0.6 (silica gel, methylene chloride / ethanol / ammonia = 5: 2: 0.01)
  C ₃₀ H ₃₄ N ₄ O ₅ S
  ESI mass spectrum: m / z = 563 [M + H ⁺ ]
• 16. 3-Z- [1- (4- (N-Dimethylaminocarbonylmethyl-N-methylsulfonyl-amine) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (N-dimethylaminocarbonylmethyl-N-methylsulfonyl) amino) aniline
  R _f value: 0.6 (silica gel, methylene chloride / ethanol = 10: 1)
  C ₂₉ H ₃₀ N ₄ O ₆ S
  ESI mass spectrum: m / z = 561 [M - H ^- ]
• 17. 3-Z- [1- (4- (imidazol-4-yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (imidazol-4-yl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / ethanol / ammonia = 10: 1: 0.01)
  C ₂₇ H ₂₂ N ₄ O ₃
  Mass spectrum: m / z = 450 [M ⁺ ]
• 18. 3-Z- [1- (4- (tetrazol-5-yl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (tetrazol-5-yl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / ethanol = 5: 1)
  C ₂₅ H ₂₀ N ₆ O ₃
  ESI mass spectrum: m / z = 451 [M - H ^- ]
• 19. 3-Z- [1- (4- (N-benzyl-N-methylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (N-benzyl-N-methyl-aminomethyl) aniline
  R _f value: 0.4 (silica gel, methylene chloride / ethanol = 10: 1)
  C ₃₃ H ₃₁ N ₃ O ₃
  ESI mass spectrum: m / z = 516 [M - H ^- ]
• 20. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-propionylamino) aniline) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- [N- (2-dimethylaminoethyl) -N-propionylamino] aniline
  R _f value: 0.2 (silica gel, methylene chloride / ethanol = 5: 1)
  C ₃₁ H ₃₄ N ₄ O ₄
  ESI mass spectrum: m / z = 525 [M - H ^- ]
• 21. 3-Z- [1- (4- (pyrrolidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (pyrrolidin-1-ylmethyl) aniline
  R _f value: 0.1 (silica gel, methylene chloride / ethanol = 5: 1)
  C ₂₉ H ₂₉ N ₃ O ₃
  ESI mass spectrum: m / z = 466 [M - H ^- ]
• 22. 3-Z- [1- (4- (N-methyl-N-phenethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (N-phenethyl-N-methyl aminomethyl) aniline
  R _f value: 0.4 (silica gel, methylene chloride / ethanol = 10: 1)
  C ₃₄ H ₃₃ N ₃ O ₃
  ESI mass spectrum: m / z = 530 [M - H ^- ]
• 23. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and N-dimethylaminomethylcarbonyl-N-methyl-p-phenylenediamine
  R _f value: 0.1 (silica gel, methylene chloride / ethanol = 10: 1)
  C ₂₉ H ₃₀ N ₄ O ₄
  ESI mass spectrum: m / z = 497 [M - H ^- ]
• 24. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-ethylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and N- (2-dimethylamino-ethyl) -neethylsulfonyl-p-phenylenediamine
  R _f value: 0.6 (silica gel, methylene chloride / ethanol = 5: 1)
  C ₃₀ H ₃₄ N ₄ O ₅ S
  ESI mass spectrum: m / z = 561 [M - H ^- ]
• 25. 3-Z- [1- (4- (N-tert.butoxycarbonyl-N-ethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (N-tert-butoxycarbonyl-N-ethyl aminomethyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₂ H ₃₅ N ₃ O ₅
  ESI mass spectrum: m / z = 540 [M - H ^- ]
• 26. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-ethylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-ethylmethylene) -6-eth oxycarbonyl-2-indolinone and 4- (piperidin-1-ylmethyl) aniline
  R _f value: 0.9 (silica gel, methylene chloride / ethanol = 5: 1)
  C ₂₆ H ₃₁ N ₃ O ₃
  ESI mass spectrum: m / z = 432 [M - H ^- ]
• 27. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-methylsulfonylamino) anilino) -1-ethylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-ethylmethylene) -6-eth oxycarbonyl-2-indolinone and N- (2-dimethylamino-ethyl) -N-methylsulfonyl-p-phenylenediamine
  R _f value: 0.3 (silica gel, methylene chloride / ethanol = 5: 1)
  C ₂₅ H ₃₂ N ₄ O ₅ S
  ESI mass spectrum: m / z = 499 [M - H ^- ]
• 28. 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (dimethylaminomethyl) aniline
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 5: 1)
  C ₂₆ H ₂₅ N ₃ O ₃
  ESI mass spectrum: m / z = 428 [M + H ⁺ ]
• 29. 3-Z- [1- (4 - [(2,6-dimethylpiperidin-1-yl) methyl] anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - [(2,6-dimethylpiperidin-1-yl) methyl] aniline
  R _f value: 0.5 (RP 8, methanol / five percent saline = 4: 1)
  C ₃₁ H ₃₃ N ₃ O ₃
  ESI mass spectrum: m / z = 496 [M + H ⁺ ]
• 30. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indoli non
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (2-dimethylamino-ethyl) -N-methylsulfonyl-p-phenylenediamine
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 5: 1)
  C ₂₈ H ₃₀ N ₄ O ₅ S
  ESI mass spectrum: m / z = 533 [M - H ^- ]
• 31. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indoli non
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (3-dimethylamine-propyl) -N-methyl sulfonyl-p-phenylenediamine
  R _f value: 0.5 (aluminum oxide, methylene chloride / methanol = 30: 1)
  C ₂₉ H ₃₂ N ₄ O ₅ S
  ESI mass spectrum: m / z = 547 [M - H ^- ]
• 32. 3-Z- [1- (4- (N-Dimethylaminocarbonylmethyl-N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N-dimethylaminocarbonylmethyl-N-methylsulfonyl) amino) aniline
  R _f value: 0.5 (aluminum oxide, methylene chloride / methanol = 20: 1)
  C ₂₈ H ₂₈ N ₄ O ₆ S
  ESI mass spectrum: m / z = 547 [M - H ^- ]
• 33. 3-Z- [1- (4- (N-acetyl-N-dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N-acetyl-N-dimethylaminocar bonylmethyl) amino) aniline
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₉ H ₂₈ N ₄ O ₅
  ESI mass spectrum: m / z = 511 [M - H ^- ]
• 34. 3-Z- [1- (4- (N-Dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N-dimethylaminocarbonylmethyl) amino) aniline
  R _f value: 0.6 (aluminum oxide, methylene chloride / methanol = 30: 1)
  C ₂₇ H ₂₆ N ₄ O ₄
  ESI mass spectrum: m / z = 469 [M - H ^- ]
• 35. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (3-dimethylamino-propyl) -N-acetyl-p-phenylenediamine
  R _f value: 0.5 (aluminum oxide, methylene chloride / methanol = 20: 1)
  C ₃₀ H ₃₂ N ₄ O ₄
  ESI mass spectrum: m / z = 511 [M - H ^- ]
• 36. 3-Z- [1- (4- (N-methylaminocarbonylmethyl-N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolone non
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N-methylaminocarbonylmethyl-N-methylsulfonyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₇ H ₂₆ N ₄ O ₆ S
  ESI mass spectrum: m / z = 533 [M - H ^- ]
• 37. 3-Z- [1- (4 - ((imidazolidin-2,4-dione-5-ylidene) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((imidazolidin-2,4-dione-5-yli den) methyl) aniline
  R _f value: 0.4 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₇ H ₂₀ N ₄ O ₅
  ESI mass spectrum: m / z = 479 [M - H ^- ]
• 38. 3-Z- [1- (4- (N - ((2-Dimethylaminoethyl) carbonyl) -N-methyl amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indo linon
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N - ((2-dimethylaminoethyl) carbonyl) -N-methyl-p-phenylenediamine
  R _f value: 0.5 (aluminum oxide, methylene chloride / methanol = 20: 1)
  C ₂₉ H ₃₀ N ₄ O ₄
  ESI mass spectrum: m / z = 497 [M - H ^- ]
• 39. 3-Z- [1- (4- (N-tert.Butoxycarbonylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N-tert-butoxycarbonyl aminomethyl) aniline
  R _f value: 0.3 (aluminum oxide, methylene chloride / methanol = 20: 1)
  C ₂₉ H ₂₉ N ₃ O ₅
  ESI mass spectrum: m / z = 498 [M - H ^- ]
• 40. 3-Z- [1- (4- (2-Oxopyrrolidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (2-oxopyrrolidin-1-ylmethyl) aniline
  R _f value: 0.3 (silica gel, methylene chloride / methanol = 20: 1)
  C ₂₈ H ₂₅ N ₃ O ₄
  ESI mass spectrum: m / z = 466 [M - H ^- ]
• 41. 3-Z- [1- (4- (N-aminocarbonylmethyl-N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N-aminocarbonylmethyl-N-methylsulfonyl-p-phenylenediamine
  R _f value: 0.7 (silica gel, methylene chloride / methanol = 5: 1)
  C ₂₆ H ₂₄ N ₄ O ₆ S
  ESI mass spectrum: m / z = 519 [M - H ^- ]
• 42. 3-Z- [1- (4- (Thiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (thiomorpholin-4-ylmethyl) aniline
  R _f value: 0.4 (silica gel, methylene chloride / methanol = 15: 1)
  C ₂₈ H ₂₇ N ₃ O ₃ S
  ESI mass spectrum: m / z = 484 [M - H ^- ]
• 43. 3-Z- [1- (4- (1,1-Dioxothiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (1,1-dioxothiomorpholin-4-ylmethyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₈ H ₂₇ N ₃ O ₅ S.
  ESI mass spectrum: m / z = 516 [M - H ^- ]
• 44. 3-Z- [1- (4- (N-cyanomethyl-N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N-cyanomethyl-N-methylsulfonyl-p-phenylenediamine
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₆ H ₂₂ N ₄ O ₅ S
  ESI mass spectrum: m / z = 501 [M - H ^- ]
• 45. 3-Z- [1- (4- (N-tert-butoxycarbonyl-ethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N-ethyl-N-tert.butoxycarbonyl aminomethyl) aniline
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₁ H ₃₃ N ₃ O ₅
  ESI mass spectrum: m / z = 526 [M - H ^- ]
• 46. 3-Z- [1- (4- (N-Benzyl-N-methylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N-benzyl-N-methylaminomethyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₂ H ₂₉ N ₃ O ₃
  ESI mass spectrum: m / z = 502 [M - H ^- ]
• 47. 3-Z- [1- (4- (1-Oxo-thiomorpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (1-oxo-thiomorpholin-4-ylmethyl) aniline
  R _f value: 0.7 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₈ H ₂₇ N ₃ O ₄ S.
  ESI mass spectrum: m / z = 500 [M - H ^- ]
• 48. 3-Z- [1- (4- (2- (imidazol-4-yl) ethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (2- (imidazol-4-yl) ethyl) aniline
  R _f value: 0.4 (silica gel, methylene chloride / methanol = 5: 1)
  C ₂₈ H ₂₄ N ₄ O ₃
  ESI mass spectrum: m / z = 463 [M - H ^- ]
• 49. 3-Z- [1- (4- (morpholin-4-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (morpholin-4-ylmethyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₈ H ₂₇ N ₃ O ₄
  ESI mass spectrum: m / z = 468 [M - H ^- ]
• 50. 3-Z- [1- (4 - ((4-Methylpiperazin-1-yl) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((4-methylpiperazin-1-yl) methyl) aniline
  R _f value: 0.4 (silica gel, methylene chloride / methanol 5: 1)
  C ₂₉ H ₃₀ N ₄ O ₃
  ESI mass spectrum: m / z = 481 [M - H ^- ]
• 51. 3-Z- [1- (4 - ((2- (N-Benzyl-N-methylamino) -ethyl) -N-methylsulfonylamino) anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2- (N-benzyl-N-methylamino) - ethyl) - N-methylsulfonylamino) aniline
  R _f value: 0.7 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₄ H ₃₄ N ₄ O ₅ S
  ESI mass spectrum: m / z = 609 [M - H ^- ]
• 52. 3-Z- [1- (4-Cyclohexylamino-anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N-cyclohexyl-p-phenylenediamine
  R _f value: 0.8 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₉ H ₂₈ N ₂ O ₃
  ESI mass spectrum: m / z = 451 [M - H ^- ]
• 53. 3-Z- [1- (4- (pyridin-4-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (pyridin-4-ylmethyl) aniline
  R _f value: 0.6 (silica gel, methylene chloride / methanol / ammonia = 5: 1: 0.01)
  C ₂₉ H ₂₃ N ₃ O ₃
  ESI mass spectrum: m / z = 460 [M - H ^- ]
• 54. 3-Z- [1- (4- (Imidazol-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (imidazol-1-ylmethyl) aniline
  R _f value: 0.4 (silica gel, methylene chloride / methanol / ammonia = 10: 1: 0.01)
  C ₂₇ H ₂₂ N ₄ O ₃
  ESI mass spectrum: m / z = 449 [M - H ^- ]
• 55. 3-Z- [1- (4- (imidazol-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (imidazol-1-ylmethyl) aniline
  R _f value: 0.4 (silica gel, methylene chloride / methanol / ammonia = 10: 1: 0.01)
  C ₂₇ H ₂₂ N ₄ O ₃
  ESI mass spectrum: m / z = 449 [M - H ^- ]
• 56. 3-Z- [1- (N-methylpiperidin-4-ylamino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4-amino-1-methyl-piperidine
  R _f value: 0.3 (silica gel, methylene chloride / methanol = 5: 1)
  C ₂₃ H ₂₅ N ₃ O ₃
  ESI mass spectrum: m / z = 390 [M - H ^- ]
• 57. 3-Z- [1- (4- (Imidazol-4-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (imidazol-4-ylmethyl) aniline
  R _f value: 0.2 (silica gel, methylene chloride / methanol = 5: 1)
  C ₂₇ H ₂₂ N ₄ O ₃
  ESI mass spectrum: m / z = 449 [M - H ^- ]
• 58. 3-Z- [1- (4 - ((4-Hydroxy-piperidin-1-yl) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((4-hydroxy-piperidin-1-yl) methyl) aniline
  R _f value: 0.1 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₉ H ₂₉ N ₃ O ₃
  ESI mass spectrum: m / z = 482 [M - H ^- ]
• 59. 3-Z- [1- (4 - ((4-Methoxy-piperidin-1-yl) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((4-methoxy-piperidin-1-yl) methyl) aniline
  R _f value: 0.4 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₀ H ₃₁ N ₃ O ₄
  ESI mass spectrum: m / z = 496 [M - H ^- ]
• 60. 3-Z- [1- (4-benzylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4-benzyl-aniline
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₀ H ₂₄ N ₂ O ₃
  Melting point: 224 ° C
• 61. 3-Z- [1- (4- (N- (3-Trifluoroacetylamino-propyl) -N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (3-trifluoroacetylamino-propyl) - N-methylsulfonyl-p-phenylenediamine
  R _f value: 0.5 (aluminum oxide, methylene chloride / methanol = 20: 1)
  C ₂₉ H ₂₇ F ₃ N ₄ O ₆ S
  ESI mass spectrum: m / z = 615 [M - H ^- ]
• 62. 3-Z- [1- (4-tert-butoxycarbonylmethylanilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-eth oxycarbonyl-2-indolinone and 4-aminophenylacetic acid tert.butyl ester
  R _f value: 0.5 (aluminum oxide, ethyl acetate)
  C ₃₀ H ₃₀ N ₂ O ₅
  ESI mass spectrum: m / z = 497 [M - H ^- ]
• 63. 3-Z- [1- (4-tert-butoxycarbonyl-anilino) -1-ethylmethylene] - 6-ethoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-ethylmethylene) -6-eth oxycarbonyl-2-indolinone and 4-tert-butoxycarbonyl-aniline
  R _f value: 0.4 (aluminum oxide, methylene chloride / ethanol = 20: 1)
  C ₂₅ H ₂₈ N ₂ O ₅
  ESI mass spectrum: m / z = 435 [M - H ^- ]
• 64. 3-Z- [1- (4- (4-tert-butoxycarbonyl-piperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (4-tert-butoxycarbonyl piperazin-1-ylmethyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₃ H ₃₆ N ₄ O ₅
  ESI mass spectrum: m / z = 567 [M - H ^- ]
• 65. 3-Z- [1- (4- (1-Methylimidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (1-methylimidazol-2-yl) aniline
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 5: 1)
  C ₂₇ H ₂₂ N ₄ O ₃
  ESI mass spectrum: m / z = 449 [M - H ^- ]
• 66. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonylamino) -3-nitro-anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 6- (N- (2-dimethylaminoethyl) - N-methylsulfonylamino) -3-amino -nitrobenzene
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 5: 1)
  C ₂₈ H ₂₉ N ₅ O ₇ S
  ESI mass spectrum: m / z = 578 [M - H ^- ]
• 67. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonylamino) -3-amino-anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylamino-ethyl) - N-methylsulfonylamino) -3-amino -aniline
  R _f value: 0.5 (aluminum oxide, methylene chloride / methanol = 20: 1)
  C ₂₅ H ₃₁ N ₅ O ₅ S
  ESI mass spectrum: m / z = 548 [M - H ^- ]
• 68. 3-Z- [1- (4 - ((3- (N-Benzyl-N-methylamino) propyl) -N-methyl sulfonylamino) anilino) -1-phenylmethylene] -6 -methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (3- (N-benzyl-N-methylamino) propyl) - N-methylsulfonylamino) aniline
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₅ H ₃₆ N ₄ O ₅ S
  ESI mass spectrum: m / z = 623 [M - H ^- ]
• 69. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonylamino) -3-chloro-anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylamino-ethyl) - N-methylsulfonylamino) -3-chlorine -aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₈ H ₂₉ ClN ₄ O ₅ S
  ESI mass spectrum: m / z = 567/569 [M - H ^- ]
• 70. 3-Z- [1- (4- (N-dimethylaminomethylcarbonyl-N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N-dimethylaminomethylcarbonyl-N-methyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₈ H ₂₈ N ₄ O ₄
  ESI mass spectrum: m / z = 483 [M - H ^- ]
• 71. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-acetylamino) ananol) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylaminoethyl) - N-acetylamino) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₉ H ₃₀ N ₄ O ₄
  ESI mass spectrum: m / z = 497 [M - H ^- ]
• 72. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-propionylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylaminoethyl) - N-propionylamino) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₀ H ₃₂ N ₄ O ₄
  ESI mass spectrum: m / z = 511 [M - H ^- ]
• 73. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-butyrylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylaminoethyl) - N-butyrylamino) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₁ H ₃₄ N ₄ O ₄
  ESI mass spectrum: m / z = 525 [M - H ^- ]
• 74. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-isobutyrylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylamino-ethyl) - N-isobutyrylamino) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₁ H ₃₄ N ₄ O ₄
  ESI mass spectrum: m / z = 525 [M - H ^- ]
• 75. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-benzoylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylamino-ethyl) - N-benzoyl-amino) -aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₄ H ₃₂ N ₄ O ₄
  ESI mass spectrum: m / z = 559 [M - H ^- ]
• 76. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-acetylamino) -3-amino-anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylamino-ethyl) - N-acetylamino) -3-amino -aniline
  R _f value: 0.5 (aluminum oxide, methylene chloride / methanol = 20: 1)
  C ₂₉ H ₃₁ N ₅ O ₄
  ESI mass spectrum: m / z = 512 [M - H ^- ]
• 77. 3-Z- [1- (4- (4-hydroxymethyl-piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (4-hydroxymethyl-piperidin-1-ylmethylamino) aniline
  R _f value: 0.3 (silica gel, methylene chloride / methanol = 5: 1)
  C ₃₀ H ₃₁ N ₃ O ₄
  ESI mass spectrum: m / z = 496 [M - H ^- ]
• 78. 3-Z- [1- (4- (2- (4-Hydroxy-piperidin-1-yl) ethyl) anilino) 1-phenyl-me from 1-acetyl-3- (1-ethoxy- 1-phenylmethylene) -6-methylene] -6-methoxycarbonyl-2-indolinone
  Manufactured toxycarbonyl-2-indolinone and 4- (2- (4-hydroxypiperidin-1-yl) ethyl amino) aniline
  R _f value: 0.3 (silica gel, methylene chloride / methanol = 5: 1)
  C ₃₀ H ₃₁ N ₃ O ₄
  ESI mass spectrum: m / z = 496 [M - H ^- ]
• 79. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-propylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (2-dimethylamino-ethyl) -N-propylsulfonyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₀ H ₃₄ N ₄ O ₅ S
  ESI mass spectrum: m / z = 561 [M - H ^- ]
• 80. -Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-butylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxyca 99999 00070 552 001000280000000200012000285919988800040 0002010042696 00004 99880rbonyl-2-indolinone and N- (2-dimethylamino-ethyl) -N-butylsulfonyl phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₁ H ₃₆ N ₄ O ₅ S
  ESI mass spectrum: m / z = 575 [M - H ^- ]
• 81. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-phenylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (2-dimethylamino-ethyl) -N-phenylsulfonyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₃ H ₃₂ N ₄ O ₅ S
  ESI mass spectrum: m / z = 595 [M - H ^- ]
• 82. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-benzylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (2-dimethylamino-ethyl) -N-ben cylsulfonyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₄ H ₃₄ N ₄ O ₅ S
  ESI mass spectrum: m / z = 609 [M - H ^- ]
• 83. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-ethylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (2-dimethylamino-ethyl) -N-ethyl sulfonyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₉ H ₃₂ N ₄ O ₅ S
  ESI mass spectrum: m / z = 547 [M - H ^- ]
• 84. 3-Z- [1- (4 - ((imidazolidin-2,4-dione-5-yl) methyl) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((imidazolidin-2,4-dione-5-yl) methyl) aniline
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 5: 1)
  C ₂₇ H ₂₂ N ₄ O ₅
  ESI mass spectrum: m / z = 481 [M - H ^- ]
• 85. 3-Z- [1- (4 - ((3-Hydroxy-pyrrolidin-1-yl) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((3-hydroxy-pyrrolidin-1-yl) methyl) aniline
  R _f value: 0.1 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₈ H ₂₇ N ₃ O ₄
  ESI mass spectrum: m / z = 468 [M - H ^- ]
• 86. 3-Z- [1- (4- (Cyclohexylylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (cyclohexylmethyl) aniline (Eur. J. Med. Chem. Chim. Ther. 1992 , 27, 537-544)
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₀ H ₃₀ N ₂ O ₃
  ESI mass spectrum: m / z = 465 [M - H ^- ]
• 87. 3-Z- [1- (4- (Cyclohexylcarbonyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (cyclohexylcarbonyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₀ H ₂₈ N ₂ O ₄
  ESI mass spectrum: m / z = 479 [M - H ^- ]
• 88. 3-Z- [1- (4-Diethylaminomethyl-anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (diethylamino-methyl) aniline
  R _f value: 0.4 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₈ H ₂₉ N ₃ O ₃
  ESI mass spectrum: m / z = 454 [M - H ^- ]
• 89. 3-Z- [1- (4- (N- (n-Hexyl) -N-methylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (n-hexyl) -N-methylamino methyl) aniline
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₁ H ₃₅ N ₃ O ₃
  ESI mass spectrum: m / z = 496 [M - H ^- ]
• 90. 3-Z- (1- (4- (N- (2-Dimethylaminoethyl) -N- (furan-2-car bonyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl -2- indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylamino-ethyl) - N- (furan-2-carbonyl) - amino) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₂ H ₃₀ N ₄ O ₅
  ESI mass spectrum: m / z = 549 [M - H ^- ]
• 91. 3-Z- (1- (4- (N- (2-Dimethylaminoethyl) -N- (2-methoxybenzoyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2 -indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylamino-ethyl) -N- (2-methoxy-benzoyl) - amino) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₅ H ₃₄ N ₄ O ₅
  ESI mass spectrum: m / z = 589 [M - H ^- ]
• 92. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N- (pyridin-3-car bonyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl -2- indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylamino-ethyl) - N- (pyridine-3-carbonyl) - amino) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₃ H ₃₁ N ₅ O ₄
  ESI mass spectrum: m / z = 560 [M - H ^- ]
• 93. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N- (phenylacetyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylamino-ethyl) - N- (phenyl-acetyl) amino) -aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₅ H ₃₄ N ₄ O ₄
  ESI mass spectrum: m / z 573 [M - H ^- ]
• 94. 3-Z- [1- (4- (N-ethyl-N-methylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N-ethyl-N-methylaminomethyl) aniline
  R _f value: 0.3 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₇ H ₂₇ N ₃ O ₃
  ESI mass spectrum: m / z = 440 [M - H ^- ]
• 95. 3-Z- [1- (4- (imidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (imidazol-2-yl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₆ H ₂₀ N ₄ O ₃
  ESI mass spectrum: m / z = 435 [M - H ^- ]
• 96. 3-Z- [1- (4- (1-Ethylimidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (1-ethyl-imidazol-2-yl) aniline
  R _f value: 0.4 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₈ H ₂₄ N ₄ O ₃
  ESI mass spectrum: m / z = 463 [M - H ^- ]
• 97. 3-Z- [1- (4- (1-Benzylimidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (1-benzyl-imidazol-2-yl) aniline
  R _f value: 0.3 (silica gel, methylene chloride / methanol = 20: 1)
  C ₃₃ H ₂₆ N ₄ O ₃
  ESI mass spectrum: m / z = 525 [M - H ^- ]
• 98. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-isopropylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indoline
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (2-dimethylamino-ethyl) -N-iso propylsulfonyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₀ H ₃₄ N ₄ O ₅ S
  ESI mass spectrum: m / z = 561 [M - H ^- ]
• 99. 3-Z- [1- (4- (N- (Piperidin-1-ylmethylcarbonyl) -N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonylcarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (piperidin-1-ylmethylcarbonyl) - N-methyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₁ H ₃₂ N ₄ O ₄
  ESI mass spectrum: m / z = 523 [M - H ^- ]
• 100. 3-Z- [1- (4- (N- (Morpholin-4-ylmethylcarbonyl) -N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (morpholin-4-ylmethylcarbonyl) - N-methyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₀ H ₃₀ N ₄ O ₅
  ESI mass spectrum: m / z = 525 [M - H ^- ]
• 101. 3-Z- [1- (4- (N - ((4-Benzylpiperazin-1-yl) methylcarbonyl) - N-methylamino) anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N - ((4-benzyl-piperazin-1-yl) - methylcarbonyl) -N-methyl-p -phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₇ H ₃₇ N ₅ O ₄
  ESI mass spectrum: m / z = 614 [M - H ^- ]
• 102. 3-Z- [1- (4- (N- (Pyrrolidin-1-ylmethylcarbonyl) -N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (pyrrolidin-1-yl-methylcar bonyl) -N-methyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₀ H ₃₀ N ₄ O ₄
  ESI mass spectrum: m / z = 509 [M - H ^- ]
• 103. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-acetylamino) -3- bromoanilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (2-dimethylaminoethyl) - N-acetylamino) -3-bromo -aniline
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 5: 1)
  C ₂₉ H ₂₉ BrN ₄ O ₄
  ESI mass spectrum: m / z = 575/577 [M - H ^- ]
• 104. 3-Z- [1- (4- (5-Methylimidazol-4-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (5-methylimidazol-4-yl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol / ammonia = 10: 1: 0.01)
  C ₂₇ H ₂₂ N ₄ O ₃
  ESI mass spectrum: m / z = 449 [M - H ^- ]
• 105. 3-Z- [1- (4- (N - ((2-Dimethylaminoethyl) carbonyl) -N-isopropylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2 -indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N - ((2-dimethylamino-ethyl) -car bonyl) -N-isopropyl-p-phenylenediamine
  R _f value: 0.1 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₁ H ₃₄ N ₄ O ₄
  ESI mass spectrum: m / z = 525 [M - H ^- ]
• 106. 3-Z- [1- (4- (N - ((2-Dimethylaminoethyl) carbonyl) -N-benzylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N - ((2-dimethylamino-ethyl) -car bonyl) -N-benzyl-p-phenylenediamine
  R _f value: 0.1 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₁ H ₃₄ N ₄ O ₄
  ESI mass spectrum: m / z = 525 [M - H ^- ]
• 107. 3-Z- [1- (4- (N-Butyl-N-tert-butoxycarbonylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N-butyl-N-tert.butoxycarbonyl aminomethyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₃ H ₃₇ N ₃ O ₅
  ESI mass spectrum: m / z = 554 [M - H ^- ]
• 108. 3-Z- [1- (4- (N - ((N-aminocarbonylmethyl-N-methylamino) - methylcarbonyl) -N-methylamino) anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (N-aminocarbonylmethyl-N-methylamino) -methylcarbonyl) -N-methyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₉ H ₂₉ N ₅ O ₅
  ESI mass spectrum: m / z = 526 [M - H ^- ]
• 109. 3-Z- [1- (4- (N - ((N-Benzyl-N-methylamino) methylcarbonyl) - N-methylamino) anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N - ((N-benzyl-N-methylamino) - methylcarbonyl) -N-methyl-p -phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₄ H ₃₂ N ₄ O ₄
  ESI mass spectrum: m / z = 559 [M - H ^- ]
• 110. 3-Z- [1- (4- (N- (Di- (2-methoxyethyl) amino-methylcarbonyl) - N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (di- (2-methoxyethyl) amino methylcarbonyl) -N-methyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₂ H ₃₆ N ₄ O ₆
  ESI mass spectrum: m / z = 571 [M - H ^- ]
• 111. 3-Z- [1- (4- (N - ((2- (4-tert-butoxycarbonyl-piperazin-1-yl) ethyl) carbonyl) -N-methylamino) anilino) -1 -phenylmethylene] - 6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N - ((2- (4-tert-butoxycarbonyl-piperazin-1-yl) ethyl) - carbonyl) -N-methyl-p-phenylenediamine
  R _f value: 0.8 (silica gel, methylene chloride / methanol = 5: 1)
  C ₃₆ H ₄₁ N ₅ O ₆
  ESI mass spectrum: m / z = 638 [M - H ^- ]
• 112. 3-Z- [1- (4- (N - ((2- (piperidin-1-yl) ethyl) carbonyl) -N-methylamino) anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N - ((2- (piperidin-1-yl) ethyl) carbonyl) -N-methyl -p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 5: 1)
  C ₃₂ H ₃₄ N ₄ O ₄
  ESI mass spectrum: m / z = 537 [M - H ^- ]
• 113. 3-Z- [1- (4- (N - ((2- (N-benzyl-N-methylamino) -ethyl) carbonyl) -N-methylamino) anilino) -1-phenyl -methylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N - ((2- (N-benzyl-N-methylamino) ethyl) carbonyl) -N-methyl-p-phenylenediamine
  R _f value: 0.4 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₅ H ₃₄ N ₄ O ₄
  ESI mass spectrum: m / z = 573 [M - H ^- ]
• 114. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-isopropylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (dimethylaminomethylcarbonyl) -N-isopropyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₀ H ₃₂ N ₄ O ₄
  ESI mass spectrum: m / z = 511 [M - H ^- ]
• 115. 3-Z- [1- (4- (N- (Piperidin-1-ylmethylcarbonyl) -N-isopropylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (piperidin-1-ylmethylcarbonyl) - N-isopropyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₃ H ₃₆ N ₄ O ₄
  ESI mass spectrum: m / z = 551 [M - H ^- ]
• 116. 3-Z- [1- (4- (N - ((4-tert-butoxycarbonyl-piperazin-1-yl) methylcarbonyl) -N-isopropylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N - ((4-tert-butoxycarbonyl-piperazin-1-yl) -methylcarbonyl) -N- isopropyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₇ H ₄₃ N ₅ O ₆
  ESI mass spectrum: m / z = 652 [M - H ^- ]
• 117. 3-Z- [1- (4- (N - ((N-Benzyl-N-methylamino) methylcarbonyl) - N-benzylamino) anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N - ((N-benzyl-N-methylamino) - methylcarbonyl) -N-benzyl-p -phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₄₀ H ₃₆ N ₄ O ₄
  ESI mass spectrum: m / z = 635 [M - H ^- ]
• 118. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-benzylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and N- (dimethylaminomethylcarbonyl) -N-benzyl-p-phenylenediamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol 9: 1)
  C ₃₄ H ₃₂ N ₄ O ₄
  ESI mass spectrum: m / z = 559 [M - H-]
• 119. 3-Z- [1- (4- (N- (Piperidin-1-ylmethylcarbonyl) -N-benzylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (5-methylimidazol-4-yl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₇ H ₃₆ N ₄ O ₄
  ESI mass spectrum: m / z = 559 [M - H ^- ]
• 120. 3-Z- [1- (4- (1,2,4-Triazol-2-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (1,2,4-triazol-1-ylmethyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₆ H ₂₁ N ₅ O ₃
  ESI mass spectrum: m / z = 450 [M - H ^- ]
• 121. 3-Z- [1- (4- (1,2,3-Triazol-2-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (1,2,3-triazol-2-ylmethyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 20: 1)
  C ₂₆ H ₂₁ N ₅ O ₃
  ESI mass spectrum: m / z = 450 [M - H ^- ]
• 122. 3-Z- [1- (4- (1,2,3-Triazol-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (1,2,3-triazol-1-ylmethyl) aniline
  R _f value: 0.4 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₆ H ₂₁ N ₅ O ₃
  ESI mass spectrum: m / z = 450 [M - H ^- ]
• 123. 3-Z- [1- (4 - ((N-aminocarbonylmethyl-N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((N-aminocarbonylmethyl-N-methylamino) methyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₇ H ₂₆ N ₄ O ₄
  ESI mass spectrum: m / z = 469 [M - H ^- ]
• 124. 3-Z- [1- (4 - ((Di- (2-methoxyethyl) amino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((di- (2-methoxyethyl) amino) methyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₀ H ₃₃ N ₃ O ₅
  ESI mass spectrum: m / z = 514 [M - H ^- ]
• 125. 3-Z- [1- (4- (Pyrrolidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (pyrrolidin-1-ylmethyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₈ H ₂₇ N ₃ O ₃
  ESI mass spectrum: m / z = 452 [M - H ^- ]
• 126. 3-Z- [1- (4 - ((Di- (2-hydroxyethyl) amino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((di- (2-hydroxyethyl) amino) methyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₈ H ₂₉ N ₃ O ₅
  ESI mass spectrum: m / z = 486 [M - H ^- ]
• 127. 3-Z- [1- (4 - ((N-Ethoxycarbonylmethyl-N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((N-ethoxycarbonylmethyl-N-methylamino) methyl) aniline
  R _f value: 0.5 (aluminum oxide, methylene chloride / ethanol = 40: 1)
  C ₂₉ H ₂₉ N ₃ O ₅
  ESI mass spectrum: m / z = 498 [M - H ^- ]
• 128. 3-Z- [1- (4- (Azetidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (azetidin-1-ylmethyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol / ammonia = 9: 1: 0.5)
  C ₂₇ H ₂₅ N ₃ O ₃
  ESI mass spectrum: m / z = 438 [M - H ^- ]
• 129. 3-Z- [1- (4- (N-Propyl-N-tert-butoxycarbonylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N-propyl-N-tert.butoxycarbonyl aminomethyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₂ H ₃₅ N ₃ O ₅
  ESI mass spectrum: m / z = 540 [M - H ^- ]
• 130. 3-Z- [1- (4 ((N- (2- (2-methoxyethoxy) ethyl) -N-methyl amino) methyl) anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((N- (2- (2-methoxyethoxy) ethyl) -N-methyl -amino) -methyl) -aniline
  R _f value: 0.4 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₀ H ₃₃ N ₃ O ₅
  ESI mass spectrum: m / z = 514 [M - H ^- ]
• 131. 3-Z- [1- (4 - ((N- (tert-butoxycarbonyl-3-aminopropyl) -N-methylamino) methyl) anilino) -1-phenylmethylene] -6- methoxy carbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (N- (N-tert-butoxycarbonyl-3-aminopropyl) -N-methyl- aminomethyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₃ H ₃₈ N ₄ O ₅
  ESI mass spectrum: m / z = 571 [M + H ⁺ ]
• 132. 3-Z- [1- (4 - ((N- (Methylcarbamoyl-methyl) -N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((N- (methylcarbamoylmethyl) -N-methylamino) methyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₈ H ₂₈ N ₄ O ₄
  ESI mass spectrum: m / z = 483 [M - H ^- ]
• 133. 3-Z- [1- (4 - ((N- (Dimethylcarbamoyl-methyl) -N-methylamino) -methyl) -anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((N- (dimethylcarbamoylmethyl) - N-methylamino) methyl) aniline
  R _f value: 0.3 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₉ H ₃₀ N ₄ O ₄
  ESI mass spectrum: m / z = 497 [M - H ^- ]
• 134. 3-Z- [1- (4-methylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4-methyl-aniline
  R _f value: 0.4 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₄ H ₂₀ N ₂ O ₃
  ESI mass spectrum: m / z = 383 [M - H ^- ]
• 135. 3-Z- [1- (4 - ((N-Propyl-N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((N-propyl-N-methylamino) methyl) aniline
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₈ H ₂₉ N ₃ O ₃
  EST mass spectrum: m / z = 454 [M - H ^- ]
• 136. 3-Z- [1- (4 - ((N- (2-Hydroxyethyl) -N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((N- (2-hydroxyethyl) -N-methyl amino) -methyl) - aniline
  R _f value: 0.5 (aluminum oxide, methylene chloride / ethanol = 40: 1)
  C ₂₇ H ₂₇ N ₃ O ₄
  ESI mass spectrum: m / z = 456 [M - H ^- ]
• 137. 3-Z- [1- (4 - ((N- (2-Dimethylaminoethyl) -N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((N- (2-dimethylaminoethyl) -N-methylamino) methyl) -aniline
• 138. 3-Z- [1- (4 - ((N- (3-Dimethylamino-propyl) -N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((N- (3-dimethylamino-propyl) -N-methyl-amino) -methyl) -aniline
• 139. 3-Z- [1- (4 - ((N- (2-methoxyethyl) -N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4 - ((N- (2-methoxy-ethyl) -N-methyl amino) -methyl) - aniline
• 140. 3-Z- [1- (4- (3-Oxopiperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 1-acetyl-3- (1-ethoxy-1-phenylmethylene) -6-meth oxycarbonyl-2-indolinone and 4- (3-oxopiperazin-1-ylmethyl) aniline

Example 4 3-Z- [1- (4-carboxy-anilino) -1-phenylmethylene] -6-ethoxycarbon yl-2-indolinone

485 mg of 3-Z- [1- (4-tert-butoxycarbonyl-anilino) -1-phenyl-methylene] -6-ethoxycarbonyl-2-indolinone are dissolved in 15 ml of methylene chloride and 6.0 ml of trifluoroacetic acid are added. The mixture is stirred for 2 hours at room temperature. The solvent is then stripped off and the residue is recrystallized from ether.
Yield: 375 mg (87% of theory),
R _f value: 0.3 (silica gel, methylene chloride / methanol = 10: 1)
C ₂₅ H ₂₀ N ₂ O ₅
Mass spectrum: m / z = 428 [M ⁺ ]

The following compounds are prepared analogously to Example 4:

• 1. 3-Z- [1- (4-aminomethyl anilino) -1-phenylmethylene] -6-meth oxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N-tert.butoxycarbonylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  R _f value: 0.5 (silica gel, methylene chloride / methanol / ammonia = 5: 1: 0.01)
  C ₂₄ H ₂₁ N ₃ O ₃
  ESI mass spectrum: m / z = 398 [M - H ^- ]
• 2. 3-Z- [1- (4-ethylaminomethyl anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N-tert-butoxycarbonyl-ethylamino methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-dolinone
  R _f value: 0.4 (silica gel, methylene chloride / methanol / ammonia = 10: 1: 0.01)
  C ₂₆ H ₂₅ N ₂ O ₃
  ESI mass spectrum: m / z = 426 [M - H ^- ]
• 3. 3-Z- [1- (4-carboxymethyl-anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4-tert-butoxycarbonylmethyl anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  R _f value: 0.1 (aluminum oxide, methylene chloride / ethanol / ammonia = 5: 1: 0.01)
  C ₂₆ H ₂₂ N ₂ O ₅
  ESI mass spectrum: m / z = 441 [M - H ^- ]
• 4. 3-Z- [1- (4-carboxy-anilino) -1-ethylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4-tert-butoxycarbonyl-anilino) -1-ethylmethylene] -6-ethoxycarbonyl-2-indolinone
  R _f value: 0.1 (aluminum oxide, methylene chloride / ethanol = 20: 1)
  C ₂₁ H ₂₀ N ₂ O ₅
  ESI mass spectrum: m / z = 379 [M - H ^- ]
• 5. 3-Z- [1- (4- (piperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (4-tert-butoxycarbonylpiperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  R _f value: 0.1 (silica gel, methylene chloride / methanol / ammonia = 10: 1: 0.01)
  C ₂₈ H ₂₈ N ₄ O ₃
  ESI mass spectrum: m / z = 469 [M + H ⁺ ]
• 6. 3-Z- [1- (4-butylaminomethyl anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N-butyl-N-tert-butoxycarbonyl aminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₈ H ₂₉ N ₃ O ₃
  ESI mass spectrum: m / z = 454 [M - H ^- ]
• 7. 3-Z- [1- (4-Ethylaminomethyl-anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N-tert-butoxycarbonyl-N-ethyl aminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  R _f value: 0.3 (silica gel, methylene chloride / methanol / ammonia = 10: 1: 0.01)
  C ₂₇ H ₂₇ N ₃ O ₃
  ESI mass spectrum: m / z = 442 [M + H ⁺ ]
• 8. 3-Z- [1- (4-ethylaminomethyl anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone
  Made from 3-Z- [1- (4- (N-tert-butoxycarbonyl-ethylamino methyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone
  R _f value: 0.2 (silica gel, methylene chloride / methanol / ammonia = 5: 1: 0.01)
  C ₂₅ H ₂₄ N ₄ O ₂
  ESI mass spectrum: m / z = 411 [M - H ^- ]
• 9. 3-Z- [1- (4- (N- (Piperazin-1-ylmethylcarbonyl) -N-isopropylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N - ((4-tert-butoxycarbonylpiperazin-1-yl) methylcarbonyl) -N-isopropylamino) anilino) -1-phenylmethylene] -6 -methoxycarbonyl-2-indolinone
  R _f value: 0.35 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₂ H ₃₅ N ₅ O ₄
  ESI mass spectrum: m / z = 552 [M - H ^- ]
• 10. 3-Z- [1- (4- (N - ((2- (piperazin-1-yl) ethyl) carbonyl) -N-methylamino) anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N - ((2- (4-tert-butoxycarbonylpiperazin-1-yl) ethyl) carbonyl) -N-methylamino) anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
  R _f value: 0.4 (silica gel, methylene chloride / methanol / ammonia = 5: 1: 0.01)
  C ₃₁ H ₃₃ N ₅ O ₄
  ESI mass spectrum: m / z = 540 [M + H ⁺ ]
• 11. 3-Z- [1- (4- (N-propylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N-propyl-N-tert-butoxycarbonyl aminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  R _f value: 0.35 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₇ H ₂₇ N ₃ O ₃
  ESI mass spectrum: m / z = 440 [M - H ^- ]
• 12. 3-Z- [1- (4 - ((N- (3-aminopropyl) -N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
  Made from 3-Z- [1- (4 - ((N- (tert-butoxycarbonyl-3-aminopropyl) -N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl -2-indolinone
  R _f value: 0.35 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₈ H ₃₀ N ₄ O ₃
  ESI mass spectrum: m / z = 471 [M + H ⁺ ]
• 13. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(2-aminoethoxy) carbonyl] -2-indolinone
  Made from 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(2-N-tert.butoxycarbonylaminoethoxy) carbonyl] -2-indolinone

Example 5 3-Z- [1- (4-methylaminomethyl-anilino) -1-phenylmethylene] -6- ehoxycarbonyl-2-indolinone

100 mg of 3-Z- [1- (4- (N-benzyl-N-methylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone are dissolved in 20 ml of ethanol, 0.2 ml 1N hydrochloric acid was added and the mixture was hydrogenated for 70 minutes at room temperature and 50 psi hydrogen pressure. The reaction solution is filtered and the filtrate is spun in. The residue is dried at 100 ° C in a vacuum.
Yield: 50 mg (53% of theory),
R _f value: 0.3 (silica gel, methylene chloride / ethanol / ammonia = 5: 1: 0.01)
C ₂₆ H ₂₅ N ₃ O ₃
ESI mass spectrum: m / z = 426 [M - H ^- ]

The following compounds are prepared analogously to Example 5:

• 1. 3-Z- [1- (4-methylaminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N-benzyl-N-methylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  R _f value: 0.2 (silica gel, methylene chloride / methanol / ammonia = 10: 1: 0.01)
  C ₂₅ H ₂₃ N ₃ O ₃
  ESI mass spectrum: m / z = 412 [M - H ^- ]
• 2. 3-Z- [1- (4- (N- (2-Methylamino-ethyl) -N-methylsulfonyl-amino) -anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4 - ((2- (N-benzyl-N-methylamino) ethyl) -N-methylsulfonylamino) anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
  R _f value: 0.3 (silica gel, methylene chloride / methanol / ammonia = 10: 1: 0.01)
  C ₂₇ H ₂₈ N ₄ O ₅ S
  ESI mass spectrum: m / z = 519 [M - H ^- ]
• 3. 3-Z- [1- (4- (N- (2-Aminoethyl) -N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N-cyanomethyl-N-methylsultonyl-amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  R _f value: 0.5 (silica gel, methylene chloride / methanol / ammonia = 5: 1: 0.01)
  C ₂₆ H ₂₆ N ₄ O ₅ S
  ESI mass spectrum: m / z = 505 [M - H ^- ]
• 4. 3-Z- [1- (4- (N- (3-Methylamino-propyl) -N-methylsulfonylamino)) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N- (3- (N-Benzyl-N-methylamino) propyl) -N-methylsulfonylamino) anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone
  R _f value: 0.3 (silica gel, methylene chloride / methanol / ammonia = 5: 1: 0.01)
  C ₂₈ H ₃₀ N ₄ O ₅ S
  ESI mass spectrum: m / z = 533 [M - H ^- ]
• 5. 3-Z- [1- (4- (N- (Piperazin-1-ylmethylcarbonyl) -N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N - ((4-benzylpiperazin-1-yl) methylcarbonyl) -N-methylamino) anilino) -1-phenylmethylene) -6- methoxycarbonyl-2-indolinone
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₀ H ₃₁ N ₅ O ₄
  ESI mass spectrum: m / z = 524 [M - H ^- ]
• 6. 3-Z- [1- (4- (N- (Methylamino-methylcarbonyl) -N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N - ((N-Benzyl-N-methylamino) - methylcarbonyl) -N-methylamino) anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
  R _f value: 0.3 (silica gel, methylene chloride / methanol = 9: 1)
  C ₂₇ H ₂₆ N ₄ O ₄
  ESI mass spectrum: m / z = 469 [M - H ^- ]
• 7. 3-Z- [1- (4- (N - ((2-Methylamino-ethyl) carbonyl) -N-methyl amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (N - ((2- (N-benzyl-N-methylamino) ethyl) carbonyl) -N-methylamino) anilino) -1-phenyl -methylene] - 6-methoxycarbonyl-2-indolinone
  R _f value: 0.3 (silica gel, methylene chloride / methanol / ammonia = 5: 1: 0.01)
  C ₂₈ H ₂₈ N ₄ O ₄
  ESI mass spectrum: m / z = 483 [M - H ^- ]

Example 6 3-Z- [1- (4-ureidomethyl anilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone

300 mg of 3-Z- [1- (4-aminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone are dissolved in 15 ml of methanol and 200 ml of triethylamine are added. 400 mg of potassium cyanate in 5 ml of water are then added. After 2 days of stirring at room temperature, the reaction solution is spun in, the residue is taken up in methylene chloride and washed once each with water and saturated sodium chloride solution. The organic phase is dried over sodium sulfate and evaporated. The residue is dried at 100 ° C in a vacuum.
Yield: 100 mg (21% of theory),
R _f value: 0.7 (silica gel, methylene chloride / methanol = 5: 1)
C ₂₅ H ₂₂ N ₄ O ₄
ESI mass spectrum: m / z = 441 [M - H ^- ]

Example 7 3-Z- [1- (4-guanidinomethyl anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone

300 mg of 3-Z- [1- (4-aminomethyl anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone are dissolved in 5 ml of dimethylformamide and 300 ml of triethylamine are added. Then 700 mg of 3,5-dimethylpyrazole-1-carboxamide in 5 ml of dimethylformamide are added. After stirring for one day at room temperature, the reaction solution is spun in. The residue is dried at 100 ° C in a vacuum.
Yield: 200 mg (87% of theory),
R _f value: 0.1 (reversed phase RP 8, methanol / five percent saline = 6: 4)
C ₂₅ H ₂₃ N ₅ O ₃
Mass spectrum: m / z = 441 [M ⁺ ]

Example 8 3-Z- [1- (4-acetylaminomethyl-anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone

100 mg of 3-Z- [1- (4-aminomethyl-anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone are dissolved in 5 ml of glacial acetic acid, 0.1 ml of acetic anhydride are added and the mixture is stirred at room temperature for 10 minutes . After this time, the reaction solution is poured onto saturated sodium carbonate solution and extracted four times with methylene chloride. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulfate and evaporated. The residue is dried at 100 ° C in a vacuum.
Yield: 20 mg (23% of theory),
R _f value: 0.4 (silica gel, methylene chloride / methanol = 10: 1)
C ₂₆ H ₂₃ N ₃ O ₄
ESI mass spectrum: m / z = 440 [M - H ^- ]

The following compounds are produced analogously to Example 8:

• 1. 3-Z- [1- (4- (N-methylsulfonylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4-aminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone and methanesulfonyl chloride / triethylamine
  R _f value: 0.7 (silica gel, methylene chloride / methanol = 5: 1)
  C ₂₅ H ₂₃ N ₃ O ₅ S.
  ESI mass spectrum: m / z = 476 [M - H ^- ]
• 2. 3-Z- [1- (4- (4-Benzoyl-piperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (piperazin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone and benzoyl chloride
  R _f value: 0.7 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₅ H ₃₂ N ₄ O ₄
  ESI mass spectrum: m / z = 571 [M - H ^- ]
• 3. 3-Z- [1- (4 - ((N- (3-acetylamino-propyl) -N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
  Made from 3-Z- [1- (4 - ((N- (3-aminopropyl) -N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2- indolinone
  R _f value: 0.3 (silica gel, methylene chloride / methanol = 9: 1)
  C ₃₀ H ₃₂ N ₄ O ₄
  ESI mass spectrum: m / z = 511 [M - H ^- ]
• 4. 3-Z- [1- (4 - ((N- (3-Methylsulfonylamino-propyl) -N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2- indolinone
  Made from 3-Z- [1- (4 - ((N- (3-aminopropyl) -N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2- indolinone and methanesulfonyl chloride / triethylamine

Example 9 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] - 6-carboxy-2-indolinone

0.8 g of 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone are dissolved in 30 ml of ethanol, 8.3 ml of 1 N sodium hydroxide solution was added and the mixture was stirred at 80 ° C. for 1 hour. After cooling, neutralized with 8.3 ml of 1 N hydrochloric acid. The precipitate is filtered off, washed with water, ethanol and ether and dried in vacuo at 100 ° C.
Yield: 0.7 g (89% of theory),
R _f value: 0.2 (silica gel, methylene chloride / methanol = 5: 2)
C ₂₈ H ₂₇ N ₃ O ₃
Mass spectrum: m / z = 453 [M ⁺ ]

The following compounds are prepared analogously to Example 9:

• 1. 3-Z- [1- (4-bromoanilino) -1-phenylmethylene] -6-carboxy-2-indolinone
  Made from 3-Z- [1- (4-bromoanilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone
  R _f value: 0.4 (silica gel, toluene / ethyl acetate = 5: 1)
  C ₂₂ H ₁₅ BrN ₂ O ₃
  ESI mass spectrum: m / z = 435/437 [M + H ⁺ ]
• 2. 3-Z- [1- (3- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone
  Made from 3-Z- [1- (3- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  R _f value: 0.7 (reversed phase RP 8, methanol / five percent saline = 4: 1)
  C ₂₅ H ₂₃ N ₃ O ₃
  ESI mass spectrum: m / z = 414 [M + H ⁺ ]
• 3. 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone
  Made from 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  R _f value: 0.7 (reversed phase RP 8, methanol / five percent saline = 4: 1)
  C ₂₅ H ₂₃ N ₃ O ₃
  ESI mass spectrum: m / z = 412 [M - H ^- ]
• 4. 3-Z- [1- (4 - [(2,6-dimethylpiperidin-1-yl) methyl] anilino) - 1-phenylmethylene] -6-carboxy-2-indolinone
  Made from 3-Z- [1- (4 - [(2,6-dimethylpiperidin-1-yl) methyl] anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
  R _f value: 0.6 (reversed phase RP 8, methanol / five percent saline = 4: 1)
  C ₃₀ H ₃₁ N ₃ O ₃
  ESI mass spectrum: m / z = 482 [M + H ⁺ ]
• 5. 3-Z- [1- (4- (1-methylimidazol-2-yl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone
  Made from 3-Z- [1- (4- (1-methylimidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  R _f value: 0.6 (reversed phase RP 8, methanol / five percent saline = 4: 1)
  C ₂₆ H ₂₀ N ₄ O ₃
  ESI mass spectrum: m / z = 435 [M - H ^- ]
• 6. 3-Z- [1- (4- (N-acetyl-N-dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone
  Made from 3-Z- [1- (4- (N-acetyl-N-dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  R _f value: 0.3 (silica gel, methylene chloride / methanol = 10: 1)
  C ₂₈ H ₂₆ N ₄ O ₅
  ESI mass spectrum: m / z = 497 [M - H ^- ]
• 7. 3-Z- [1- (4-Ethylaminomethyl-anilino) -1-phenylmethylene] -6-carboxy-2-indolinone
  Made from 3-Z- [1- (4-ethylaminomethylanilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  R _f value: 0.6 (reversed phase RP 8, methanol / five percent saline = 4: 1)
  C ₂₅ H ₂₃ N ₃ O ₃
  ESI mass spectrum: m / z = 412 [M - H ^- ]
• 8. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methylamino) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone
  Made from 3-Z- [1- (4- (N-dimethylaminomethylcarbonyl-N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  R _f value: 0.6 (reversed phase RP 8, methanol / five percent saline = 4: 1)
  C ₂₇ H ₂₆ N ₄ O ₄
  ESI mass spectrum: m / z = 469 [M - H ^- ]
• 9. 3-Z- [1- (4- (N-tert-Butoxycarbonyl-ethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone
  Made from 3-Z- [1- (4- (N-tert-butoxycarbonyl-ethylamino methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-dolinone
  R _f value: 0.4 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₀ H ₃₁ N ₃ O ₅
  ESI mass spectrum: m / z = 512 [M - H ^- ]
• 10. 3-Z- [1- (4 - ((N-Carboxymethyl-N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4 - ((N-ethoxycarbonylmethyl-N-methylamino) methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
  R _f value: 0.4 (silica gel, methylene chloride / methanol = 6: 1)
  C ₂₇ H ₂₅ N ₃ O ₅
  ESI mass spectrum: m / z = 470 [M - H ^- ]

Example 10 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone

0.9 g of 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone are suspended in 35 ml of dimethylformamide and 0.4 g of carbonyldiimidazole admitted. The mixture is stirred at 80 ° C for 14 hours. After this time, 20 ml of methanol are added and the mixture is stirred at 50 ° C. for another 3 hours. The solvent is removed and the residue was purified on a silica gel column using methylene chloride / methanol (3: 1) as the eluent.
Yield: 0.5 g (49% of theory),
R _f value: 0.5 (aluminum oxide, methylene chloride / methanol = 30: 1)
C ₂₉ H ₂₉ N ₃ O ₃
ESI mass spectrum: m / z = 468 [M + H ⁺ ]

The following compounds are prepared analogously to Example 10:

• 1. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-benzyloxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and benzyl alcohol
  R _f value: 0.6 (aluminum oxide, methylene chloride / methanol = 30: 1)
  C ₃₅ H ₃₃ N ₃ O ₃
  Mass spectrum: m / z = 543 [M ⁺ ]
• 2. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-isopropyloxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and isopropanol
  R _f value: 0.4 (aluminum oxide, methylene chloride / isopropanol = 30: 1)
  C ₃₁ H ₃₃ N ₃ O ₃
  Mass spectrum: m / z = 495 [M ⁺ ]
• 3. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-propyloxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and n-propanol
  R _f value: 0.7 (silica gel, methylene chloride / methanol = 5: 1)
  C ₃₁ H ₃₃ N ₃ O ₃
  Mass spectrum: m / z = 495 [M ⁺ ]
• 4. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-butyloxycarbonyl-2-indolinone
  Made from 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and n-butanol
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 10: 1)
  C ₃₂ H ₃₅ N ₃ O ₃
  Mass spectrum: m / z = 509 [M ⁺ ]
• 5. 3-Z- [1- (4-bromoanilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone
  Made from 3-Z- [1- (4-bromo-anilino) -1-phenylmethylene] - 6-carboxy-2-indolinone and ammonia
  R _f value: 0.5 (silica gel, methylene chloride / methanol 10: 1)
  C ₂₂ H ₁₆ BrN ₂ O ₃
  Mass spectrum: m / z = 432/434 [M - H ^- ]
• 6. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethylcarbamoyl-2-indolinone
  Made from 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and ethylamine gas
  R _f value: 0.6 (silica gel, methylene chloride / methanol = 5: 1)
  C ₃₀ H ₃₂ N ₄ O ₂
  Mass spectrum: m / z = 480 [M ⁺ ]
• 7. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(2-methoxyethoxy) carbonyl] -2-indolinone
  Made from 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and methyl glycol
  R _f value: 0.8 (silica gel, methylene chloride / methanol = 4: 1)
  C ₂₅ H ₂₃ N ₃ O ₃
  ESI mass spectrum: m / z = 470 [M - H ^- ]
• 8. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(2-dimethylaminoethoxy) carbonyl] -2-indolinone
  Made from 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and 2-dimethylaminoethanol
• 9. 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(2-N-tert-butoxycarbonylaminoethoxy) carbonyl] -2-indolinone
  Made from 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and 2-N-tert.butoxycarbonyl-aminoethanol
• 10. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) -1-phenylmethylene] -6 - [(2,2,2-trifluoroethoxy) carbonyl] -2-indolinone
  Made from 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and 2,2,2-trifluoroethanol

Example 11 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] - 6-carbamoyl-2-indolinone

0.9 g of 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone, 0.8 g of TBTU and 0.4 g of HOBT who suspended in 25 ml of dimethylformamide and 1.0 ml of triethylamine added. The mixture is stirred for 15 minutes at room temperature. After this time, ammonia gas is introduced at 10-15 ° C for 15 minutes and stirred for 1.5 hours at room temperature. The resulting precipitate is filtered off, washed with water, ethanol and ether and dried in vacuo at 100 ° C.
Yield: 0.6 g (64% of theory),
R _f value: 0.4 (reversed phase RP 8, methanol / five percent saline = 6: 4)
C ₂₈ H ₂₈ N ₄ O ₂
ESI mass spectrum: m / z = 453 [M + H ⁺ ]

The following compounds are produced analogously to Example 11:

• 1. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-dimethylcarbamoyl-2-indolinone
  Made from 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and dimethylaminohydrochloride / diisopropylethylamine
  R _f value: 0.5 (silica gel, methylene chloride / methanol = 5: 1)
  C ₃₀ H ₃₂ N ₄ O ₂
  ESI mass spectrum: m / z = 481 [M + H ⁺ ]
• 2. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6- (N-ethyl-N-methylcarbamoyl) -2-indolinone
  Made from 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and N-ethyl-N-methylamine
  R _f value: 0.5 (aluminum oxide, methylene chloride / ethanol = 20: 1)
  C ₃₁ H ₃₄ N ₄ O ₂
  ESI mass spectrum: m / z = 495 [M + H ⁺ ]
• 3. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methylcarbamoyl-2-indolinone
  Made from 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and methylamine hydrochloride / diisopropylethylamine
  R _f value: 0.3 (aluminum oxide, methylene chloride / ethanol = 20: 1)
  C ₂₉ H ₃₀ N ₄ O ₂
  ESI mass spectrum: m / z = 467 [M + H ⁺ ]
• 4. 3-Z- [1- (3- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-methylcarbamoyl-2-indolinone
  Made from 3-Z- [1- (3- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxyl-2-indolinone and methylamine hydrochloride / triethylamine
  R _f value: 0.3 (silica gel, methylene chloride / ethanol = 2: 1)
  C ₂₆ H ₂₆ N ₄ O ₂
  Mass spectrum: m / z = 426 [M ⁺ ]
• 5. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6- (2-hydroxyethylcarbamoyl) -2-indolinone
  Made from 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and ethanolamine / diisopropylethylamine
  R _f value: 0.5 (aluminum oxide, methylene chloride / methanol = 20: 1)
  C ₃₀ H ₃₂ N ₄ O ₃
  ESI mass spectrum: m / z = 495 [M - H ^- ]
• 6. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-diethylcarbamoyl-2-indolinone
  Made from 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone and diethylaminohydrochloride / diisopropylethylamine
  R _f value: 0.8 (aluminum oxide, methylene chloride / methanol = 10: 1)
  C ₃₂ H ₃₆ N ₄ O ₂
  ESI mass spectrum: m / z = 509 [M + H ⁺ ]
• 7. 3-Z- [1- (4- (N-tert-Butoxycarbonyl-ethylaminomethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone
  Made from 3-Z- [1- (4- (N-tert-butoxycarbonylethylaminomethyl) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone
  R _f value: 0.3 (silica gel, toluene / ethyl acetate / ethanol = 4: 2: 1)
  C ₃₀ H ₃₂ N ₄ O ₄
  ESI mass spectrum: m / z = 511 [M - H ^- ]
• 8. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methylamino) anilino) -1-phenylmethylene] -6'-carbamoyl-2-indolinone
  Made from 3-Z- [1- (4- (N-dimethylaminomethylcarbonyl-N-methylamino) anilino) -1-phenylmethylene] -6-carboxy-2-indolinone
  R _f value: 0.5 (silica gel, methylene chloride / methanol / ammonia = 5: 1: 0.01)
  C ₂₇ H ₂₇ N ₅ O ₃
  ESI mass spectrum: m / z = 468 [M - H ^- ]

Example 12 3-Z- [1- (4- (N-dimethylaminomethylcarbonyl-N-methylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone × Citric acid

3.25 g of citric acid monohydrate are placed in 50 ml of methanol and 5.0 g of 3-Z- [1- (4- (N-dimethylaminomethylcarbonyl-N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2 - Indolinone added at room temperature. The resulting solution is concentrated, the residue is washed with ether and recrystallized from ethyl acetate.
Yield: 6.3 g (90% of theory),
R _f value: 0.6 (silica gel, methylene chloride / methanol / ammonia = 5: 1: 0.01)
Melting point: 198 ° C
C ₂₈ H ₂₈ N ₄ O ₅ × C ₆ H ₈ O ₇
ESI mass spectrum: m / z = 483 [M - H ^- ]
Elemental analysis:
calculated:
C 60.34; H 5.37; N 8.28
found:
C 59.98; H 5.25; N 8.13

The following connection is established analogously to Example 12:

• 1. 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone × methanesulfonic acid
  Made from 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone and methane sulfonic acid
  R _f value: 0.6 (silica gel, methylene chloride / methanol / ammonia = 5: 1: 0.01)
  Melting point: 275 ° C
  C ₂₆ H ₂₅ N ₃ O ₃ × CH ₄ O ₃ S
  ESI mass spectrum: m / z = 426 [M - H ^- ]
  Elemental analysis:
  calculated:
  C 61.92; H 5.59; N 8.03; S 6.12
  found:
  C 61.43; H 5.87; N 7.85; S 5.39

The following connections can be made analogously to the examples above:

• 1. 3-Z- (1-anilino-1-phenylmethylene) -6-ethoxycarbonyl-2-in dolinon
• 2. 3-Z- [1- (4-nitro-anilino) -1-phenylmethylene] -6-ethoxycarbo nyl-2-indolinone
• 3. 3-Z- [1- (4-fluoro-anilino) -1-phenylmethylene] -6-ethoxycar bonyl-2-indolinone  
• 4. 3-Z- [1- (4-chloro-anilino) -1-phenylmethylene] -6-ethoxycar bonyl-2-indolinone
• 5. 3-Z- [1- (4-iodo-anilino) -1-phenylmethylene] -6-ethoxycarbon yl-2-indolinone
• 6. 3-Z- [1- (4-cyano-anilino) -1-phenylmethylene] -6-ethoxycar bonyl-2-indolinone
• 7. 3-Z- [1- (4-methoxy-anilino) -1-phenylmethylene] -6-ethoxycar bonyl-2-indolinone
• 8. 3-Z- [1- (4-ethoxy-anilino) -1-phenylmethylene] -6-ethoxycar bonyl-2-indolinone
• 9. 3-Z- [1- (4-trifluoromethyl-anilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone
• 10. 3-Z- [1- (4-methyl-anilino) -1-phenylmethylene] -6-ethoxycar bonyl-2-indolinone
• 11. 3-Z- [1- (4-methylmercapto-anilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone
• 12. 3-Z- [1- (4-aminomethylanilino) -1-phenylmethylene] -6-eth oxycarbonyl-2-indolinone
• 13. 3-Z- [1- (4- (isopropylaminomethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone
• 14. 3-Z- [1- (4- (anilinomethyl) anilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone
• 15. 3-Z- [1- (4- (propylaminomethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone  
• 16. 3-Z- [1- (4- (butylaminomethyl) anilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone
• 17. 3-Z- [1- (4- (isobutylaminomethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone
• 18. 3-Z- [1- (4- (cyclohexylaminomethyl) anilino) -1-phenyl-me ethylene] -6-ethoxycarbonyl-2-indolinone
• 19. 3-Z- [1- (4- (benzylaminomethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone
• 20. 3-Z- [1- (4 - ((N-ethyl-N-methylamino) methyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 21. 3-Z- [1- (4 - ((N-methyl-N-propylamino) methyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 22. 3-Z- [1- (4 - ((N-isopropyl-N-methylamino) methyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 23. 3-Z- [1- (4 - ((N-ethyl-N-propylamino) methyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 24. 3-Z- [1- (4 - ((N-ethyl-N-isopropylamino) methyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 25. 3-Z- [1- (4- (Dipropylaminomethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone
• 26. 3-Z- [1- (4- (diisopropylaminomethyl) anilino) -1-phenyl-me ethylene] -6-ethoxycarbonyl-2-indolinone
• 27. 3-Z- [1- (4 - ((N-Benzyl-N-ethylamino) methyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone  
• 28. 3-Z- [1- (4- (dibenzylaminomethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone
• 29. 3-Z- [1- (4- (3,6-dihydro-2H-pyridin-1-ylmethyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 30. 3-Z- [1- (4- (3,5-dimethylpiperidin-1-ylmethyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 31. 3-Z- [1- (4- (azepan-1-ylmethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone
• 32. 3-Z- [1- (4- (piperazin-1-ylmethyl) anilino) -1-phenylme ethylene] -6-ethoxycarbonyl-2-indolinone
• 33. 3-Z- [1- (4- (morpholin-4-ylmethyl) anilino) -1-phenylme ethylene] -6-ethoxycarbonyl-2-indolinone
• 34. 3-Z- [1- (4- (Thiomorpholin-4-ylmethyl) anilino) -1-phenyl methylene] -6-ethoxycarbonyl-2-indolinone
• 35. 3-Z- [1- (4- (1-oxothiomorpholin-4-ylmethyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 36. 3-Z- [1- (4- (1,1-Dioxothiomorpholin-4-ylmethyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 37. 3-Z- [1- (4- (acetylamino-methyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone
• 38. 3-Z- [1- (4- (2-aminoethyl) anilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone
• 39. 3-Z- [1- (4- (2-Methylaminoethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone  
• 40. 3-Z- [1- (4- (2-Ethylaminoethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone
• 41. 3-Z- [1- (4- (2-Diethylaminoethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone
• 42. 3-Z- [1- (4- (2-piperidin-1-yl-ethyl) anilino) -1-phenyl-me ethylene] -6-ethoxycarbonyl-2-indolinone
• 43. 3-Z- [1- (4- (2-acetylaminoethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone
• 44. 3-Z- [1- (4- (3-aminopropyl) anilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone
• 45. 3-Z- [1- (4- (3-Dimethylamino-propyl) anilino) -1-phenyl-me ethylene] -6-ethoxycarbonyl-2-indolinone
• 46. 3-Z- [1- (4- (N-aminomethylcarbonyl-N-methylamino) -anili no) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 47. 3-Z- [1- (4- (N-methylaminomethylcarbonyl-N-methylamino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 48. 3-Z- [1- (4- (N-ethylaminomethylcarbonyl-N-methylamino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 49. 3-Z- [1- (4- (N-diethylaminomethylcarbonyl-N-methylamino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 50. 3-Z- [1- (4- (N- (Piperidin-1-yl-methylcarbonyl) -N-methyl- amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indo linon
• 51. 3-Z- [1- (4- (N- (Morpholin-4-yl-methylcarbonyl) -N-methyl- amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indo linon  
• 52. 3-Z- [1- (4- (N- (Piperazin-1-yl-methylcarbonyl) -N-methyl amino] anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indo linon
• 53. 3-Z- [1- (4- (N- (2-Aminoethylcarbonyl) -N-methylamino) -ani lino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 54. 3-Z- [1- (4- (N- (2-Methylaminoethylcarbonyl) -N-methyl-ami no) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 55. 3-Z- [1- (4- (N- (2-Diethylaminoethylcarbonyl) -N-methyl-ami no) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 56. 3-Z- [1- (4- (N-acetyl-N- (2-aminoethyl) amino) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 57. 3-Z- [1- (4- (N-acetyl-N- (2-methylamino-ethyl) amino) anili no) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 58. 3-Z- [1- (4- (N-acetyl-N- (2-methylamino-propyl) amino) -ani lino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 59. 3-Z- [1- (4- (N-acetyl-N- (2-piperidin-1-yl-ethyl) amino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 60. 3-Z- [1- (4- (N-acetyl-N- (aminocarbonylmethyl) amino) anili no) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 61. 3-Z- [1- (4- (N-acetyl-N- (dimethylaminocarbonylmethyl) -ami no) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 62. 3-Z- [1- (4- (N-acetyl-N- (piperidin-1-yl-carbonylmethyl) - amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indo linon  
• 63. 3-Z- [1- (4- (N-methyl-N- (aminocarbonyl) amino) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 64. 3-Z- [1- (4- (N-methyl-N- (methylaminocarbonyl) amino) anili no) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 65. 3-Z- [1- (4- (N-methyl-N- (dimethylaminocarbonyl) amino) -ani lino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 66. 3-Z- [1- (4- (N-methyl-N- (piperidin-1-ylcarbonyl) amino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 67. 3-Z- [1- (4- (N- (2-Aminoethyl) -N-methylsulfonylamino) -ani lino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 68. 3-Z- [1- (4- (N- (2-Methylamino-ethyl) -N-methylsulfonyl-ami no) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 69. 3-Z- [1- (4- (N- (2-Ethylamino-ethyl) -N-methylsulfonyl-ami no) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 70. 3-Z- [1- (4- (N- (2-Diethylamino-ethyl) -N-methylsulfonyl-ami no) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 71. 3-Z- [1- (4- (N- (2-Pyrrolidin-1-yl-ethyl) -N-methylsulfonyl- amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indo linon
• 72. 3-Z- [1- (4- (N- (2-Piperidin-1-yl-ethyl) -N-methylsulfonyl- amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indo linon
• 73. 3-Z- [1- (4- (N- (2-Piperazin-1-yl-ethyl) -N-methylsulfonyl- amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon  
• 74. 3-Z- [1- (4- (N- (2- (morpholin-4-yl) ethyl) -N-methylsulfonyl- amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 75. 3-Z- [1- (4- (N- (Aminocarbonylmethyl) -N-methylsulfonyl-ami no) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 76. 3-Z- [1- (4- (N- (Methylaminocarbonylmethyl) -N-methylsulfo nylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 77. 3-Z- [1- (4- (N- (Ethylaminocarbonylmethyl) -N-methylsulfonyl amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 78. 3-Z- [1- (4- (N- (N- (2-Dimethylaminoethyl) -N-methylamino) - carbonylmethyl) -N-methylsulfonyl-amino) -anilino) -1-phenyl-me ethylene] -6-ethoxycarbonyl-2-indolinone
• 79. 3-Z- [1- (4- (N- (Diethylaminocarbonylmethyl) -N-methylsul fonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 80. 3-Z- [1- (4- (N- (Pyrrolidin-1-ylcarbonylmethyl) -N-methyl sulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinion
• 81. 3-Z- [1- (4- (N- (Piperidin-1-ylcarbonylmethyl) -N-methylsul fonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 82. 3-Z- [1- (4- (N- (Piperazin-1-ylcarbonylmethyl) -N-methylsul fonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone  
• 83. 3-Z- [1- (4- (N - ((Morpholin-4-yl) carbonylmethyl) -N-methyl sulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 84. 3-Z- [1- (4- (2-Dimethylaminoethoxy) anilino) -1-phenylme ethylene] -6-ethoxycarbonyl-2-indolinone
• 85. 3-Z- [1- (4- (3-Dimethylamino-propoxy) anilino) -1-phenyl- methylene] -6-ethoxycarbonyl-2-indolinone
• 86. 3-Z- [1- (4- (aminocarbonylmethyl) anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone
• 87. 3-Z- [1- (4- (2-aminocarbonylethyl) anilino) -1-phenylme ethylene] -6-ethoxycarbonyl-2-indolinone
• 88. 3-Z- [1- (4- (pyridin-2-yl) anilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone
• 89. 3-Z- [1- (4- (pyridin-3-yl) anilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone
• 90. 3-Z- [1- (4- (pyridin-4-yl) anilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone
• 91. 3-Z- [1- (4- (N-acetyl-N-methylamino) anilino) -1-phenyl-me ethylene] -6-ethoxycarbonyl-2-indolinone
• 92. 3-Z- [1- (4- (N-ethylcarbonyl-N- (dimethylaminocarbonylme thyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 93. 3-Z- [1- (carbamoylmethyl anilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone
• 94. 3-Z- [1- (4-dimethylcarbamoylmethyl anilino) -1-phenyl methylene] -6-ethoxycarbonyl-2-indolinone  
• 95. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) methylene] - 6-ethoxycarbonyl-2-indolinone
• 96. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) propylidene] -6- ethoxycarbonyl-2-indolinone
• 97. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) butylidene] - 6-ethoxycarbonyl-2-indolinone
• 98. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) - anilino) methylene] -6-ethoxycarbonyl-2-indolinone
• 99. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) - anilino) ethylidene] -6-ethoxycarbonyl-2-indolinone
• 100. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) - anilino) propylidene] -6-ethoxycarbonyl-2-indolinone
• 101. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) - anilino) butylidene] -6-ethoxycarbonyl-2-indolinone
• 102. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-methylsulfonyl- amino) anilino) methylene] -6-ethoxycarbonyl-2-indolinone
• 103. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-methylsulfonyl- amino) anilino) propylidene] -6-ethoxycarbonyl-2-indolinone
• 104. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonyl- amino) anilino) butylidene] -6-ethoxycarbonyl-2-indolinone
• 105. 3-Z- [1- (4-tetrazol-5-yl-anilino) methylene] -6-ethoxycar bonyl-2-indolinone
• 106. 3-Z- [1- (4-tetrazol-5-yl-anilino) ethylidene] -6-ethoxy carbonyl-2-indolinone  
• 107. 3-Z- [1- (4-tetrazol-5-yl-anilino) propylidene] -6-ethoxy carbonyl-2-indolinone
• 108. 3-Z- [1- (4-tetrazol-5-yl-anilino) butylidene] -6-ethoxycar bonyl-2-indolinone
• 109. 3-Z- [1- (4-carboxy-anilino) -methylene] -6-ethoxycarbonyl- 2-indolinone
• 110. 3-Z- [1- (4-carboxy-anilino) propylidene] -6-ethoxycarbonyl- 2-indolinone
• 111. 3-Z- [1- (4-carboxy-anilino) butylidene] -6-ethoxycarbonyl- 2-indolinone
• 112. 3-Z- [1- (4- (N- (3-Dimethylamino-propionyl) -N- dimethylaminocarbonylmethylamino) anilino) -1-phenyl methylene] -6-ethoxycarbonyl-2-indolinone
• 113. 3-Z- [1- (4- (N- (4-Dimethylamino-butyryl) -N-dimethyl aminocarbonylmethylamino) anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 114. 3-Z- [1- (4- (N-Dimethylaminocarbonylmethyl-N- (2- dimethylamino-ethylsulfonyl) amino) anilino) -1-phenyl methylene] -6-ethoxycarbonyl-2-indolinone
• 115. 3-Z- [1- (4- (N-Dimethylaminocarbonylmethyl-N- (3- dimethylamino-propylsulfonyl) amino) anilino) -1-phenyl methylene] -6-ethoxycarbonyl-2-indolinone
• 116. 3-Z- [1- (4 - ((2-Hydroxyethyl) amino methyl) anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 117. 3-Z- [1- (4 - ((2-methoxyethyl) amino methyl) anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone  
• 118. 3-Z- [1- (4 - ((2-Dimethylamino-ethyl) -amino-methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 119. 3-Z- [1- (4 - ((3-Dimethylamino-propyl) -amino-methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 120. 3-Z- [1- (4 - ((N-tert-butoxycarbonyl-2-amino-ethyl) amino methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone
• 121. 3-Z- [1- (4 - ((N-tert-butoxycarbonyl-3-aminopropyl) amino methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone
• 122. 3-Z- [1- (4 - ((2-Amino-ethyl) -amino-methyl) -anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 123. 3-Z- [1- (4 - ((3-Amino-propyl) -amino-methyl) -anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 124. 3-Z- [1- (4 - ((2-Acetylamino-ethyl) -amino-methyl) -anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 125. 3-Z- [1- (4 - ((3-acetylamino-propyl) -amino-methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 126. 3-Z- [1- (4 - ((2-Methylsulfonylamino-ethyl) -amino-methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 127. 3-Z- [1- (4 - ((3-Methylsulfonylamino-propyl) -amino-methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 128. 3-Z- [1- (4- (N- (N-tert-Butoxycarbonyl-2-amino-ethyl) -N- methylamino methyl) anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone  
• 129. 3-Z- [1- (4- (N- (2-Aminoethyl) -N-methylamino-methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 130. 3-Z- [1- (4- (N- (2-Acetylaminoethyl) -N-methylamino methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone
• 131. 3-Z- [1- (4- (N- (2-Methylsulfonylamino-ethyl) -N-methyl aminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone
• 132. 3-Z- [1- (4- (Carboxymethylaminomethyl) anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 133. 3-Z- [1- (4- (Ethoxycarbonylmethylaminomethyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 134. 3-Z- [1- (4- (carbamoylmethylamino-methyl) anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 135. 3-Z- [1- (4- (dimethylcarbamoyl-methylamino-methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 136. 3-Z- [1- (4- (methylcarbamoyl-methylamino-methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 137. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-amino-anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone
• 138. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-nitro-anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone
• 139. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-acetylamino-anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone  
• 140. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-methylsulfonylamino-anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 141. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-cyano-anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone
• 142. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-hydroxy-anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 143. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-methoxy-anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 144. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-ethoxycarbonyl-anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 145. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-carboxy-anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 146. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-carbamoyl-anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 147. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-chloro-anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone
• 148. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-fluoro-anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone  
• 149. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-bromo-anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone
• 150. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-methyl-anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 151. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3-trifluoromethyl-anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 152. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3,5-dibromo-anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 153. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) -3,5-dichloro-anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 154. 3-Z- [1- (4- (Dimethylaminomethyl) -3-amino-anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 155. 3-Z- [1- (4- (Dimethylaminomethyl) -3-nitro-anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 156. 3-Z- [1- (4- (Dimethylaminomethyl) -3-acetylamino-anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 157. 3-Z- [1- (4- (dimethylaminomethyl) -3- (methylsulfonylamino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 158. 3-Z- [1- (4- (dimethylaminomethyl) -3-cyano-anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 159. 3-Z- [1- (4- (dimethylaminomethyl) -3-hydroxy-anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone  
• 160. 3-Z- [1- (4- (dimethylaminomethyl) -3-methoxy-anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 161. 3-Z- [1- (4- (Dimethylaminomethyl) -3- (ethoxycarbonyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 162. 3-Z- [1- (4- (Dimethylaminomethyl) -3-carboxy-anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 163. 3-Z- [1- (4- (Dimethylaminomethyl) -3-carbamoyl-anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 164. 3-Z- [1- (4- (Dimethylaminomethyl) -3-chloro-anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 165. 3-Z- [1- (4- (Dimethylaminomethyl) -3-fluoro-anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 166. 3-Z- [1- (4- (dimethylaminomethyl) -3-bromoanilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 167. 3-Z- [1- (4- (Dimethylaminomethyl) -3-methyl-anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 168. 3-Z- [1- (4- (Dimethylaminomethyl) -3-trifluoromethyl anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 169. 3-Z- [1- (4- (dimethylaminomethyl) -3,5-dibromo-anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 170. 3-Z- [1- (4- (dimethylaminomethyl) -3,5-dichloro-anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 171. 3-Z- [1- (4- (N - ((4-Methylpiperazin-1-yl) methylcarbonyl) - N-methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone  
• 172. 3-Z- [1- (4- (N- (Imidazo-1-yl-methylcarbonyl) -N-methyl amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone
• 173. 3-Z- [1- (4- (N- (Phthalimido-2-yl-methylcarbonyl) -N-methyl amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone
• 174. 3-Z- [1- (4- (N-aminomethylcarbonyl-N-methylamino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 175. 3-Z- [1- (4- (N-acetylaminomethylcarbonyl-N-methylamino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 176. 3-Z- [1- (4- (N-Methylsulfonylaminomethylcarbonyl-N-methyl amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2- indolinone
• 177. 3-Z- [1- (4- (N - ((N- (2-methoxyethyl) -N-methylamino) - methylcarbonyl) -N-methyl-amino) -anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 178. 3-Z- [1- (4- (N - ((N- (2-Dimethylaminoethyl) -N-methylamino) - methylcarbonyl) -N-methyl-amino) -anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 179. 3-Z- [1- (4- (N - ((di- (2-hydroxyethyl) amino) - methylcarbonyl) -N-methyl-amino) -anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 180. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl-ami no) -anilino) -methylene] -6-ethoxycarbonyl-2-indolinone
• 181. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl-ami no) anilino) ethylidene] -6-ethoxycarbonyl-2-indolinone  
• 182. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl-ami no) -anilino) -propylidene] -6-ethoxycarbonyl-2-indolinone
• 183. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl-ami no) -anilino) -butylidene] -6-ethoxycarbonyl-2-indolinone
• 184. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) methylene] -6- ethoxycarbonyl-2-indolinone
• 185. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) ethylidene] -6- ethoxycarbonyl-2-indolinone
• 186. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) propylidene] -6- ethoxycarbonyl-2-indolinone
• 187. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) butylidene] -6- ethoxycarbonyl-2-indolinone
• 188. 3-Z- [1- (4- (N-dimethylaminocarbonylmethylamino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 189. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 190. 3-Z- [1- (4 - ((imidazolidin-2,4-dione-5-ylidene) methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 191. 3-Z- [1- (4- (N - ((2-Dimethylaminoethyl) carbonyl) -N- methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 192. 3-Z- [1- (4- (N-tert.butoxycarbonylaminomethyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 193. 3-Z- [1- (4- (2-Oxopyrrolidin-1-ylmethyl) anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone  
• 194. 3-Z- [1- (4- (N-aminocarbonylmethyl-N-methylsulfonyl-ami no) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 195. 3-Z- [1- (4- (N-cyanomethyl-N-methylsulfonylamino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 196. 3-Z- [1- (4- (2- (imidazol-4-yl) ethyl) anilino) -1-phenyl methylene] -6-ethoxycarbonyl-2-indolinone
• 197. 3-Z- [1- (4 - ((2- (N-benzyl-N-methylamino) ethyl) -N- methylsulfonylamino) anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 198. 3-Z- [1- (4-Cyclohexylamino-anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 199. 3-Z- [1- (4- (Imidazol-1-ylmethyl) anilino) -1-phenyl methylene] -6-ethoxycarbonyl-2-indolinone
• 200. 3-Z- [1- (4- (imidazol-1-ylmethyl) anilino) -1-phenyl methylene] -6-ethoxycarbonyl-2-indolinone
• 201. 3-Z- [1- (N-methylpiperidin-4-ylamino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone
• 202. 3-Z- [1- (4- (imidazol-4-ylmethyl) anilino) -1-phenyl methylene] -6-ethoxycarbonyl-2-indolinone
• 203. 3-Z- [1- (4 - ((4-Hydroxy-piperidin-1-yl) methyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 204. 3-Z- [1- (4 - ((4-methoxy-piperidin-1-yl) methyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 205. 3-Z- [1- (4-benzylanilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone  
• 206. 3-Z- [1- (4- (N- (3-Trifluoroacetylamino-propyl) -N-methyl sulfonylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 207. 3-Z- [1- (4- (4-tert-butoxycarbonyl-piperazin-1-yl-methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 208. 3-Z- [1- (4- (1-methylimidazol-2-yl) anilino) -1-phenyl- methylene] -6-ethoxycarbonyl-2-indolinone
• 209. 3-Z- [1- (4- (1-methylimidazol-2-yl) anilino) -1-phenyl- methylene] -6-ethoxycarbonyl-2-indolinone
• 210. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-methylsulfonyl- amino) -3-amino-anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 211. 3-Z- [1- (4 - ((3- (N-benzyl-N-methylamino) propyl) -N- methylsulfonylamino) anilino) -1-phenylmethylene] -6-ethoxy carbonyl-2-indolinone
• 212. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-acetylamino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 213. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-butyrylamino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 214. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-isobutyryl- amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 215. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-benzoyl-amino) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 216. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-acetylamino) -3- amino-anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone  
• 217. 3-Z- [1- (4- (4-hydroxymethylpiperidin-1-ylmethyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 218. 3-Z- [1- (4- (2- (4-Hydroxy-piperidin-1-yl) ethyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 219. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-propylsulfonyl amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 220. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-butylsulfonyl amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 221. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-phenylsulfonyl amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 222. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-benzylsulfonyl amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 223. 3-Z- [1- (4 - ((imidazolidin-2,4-dione-5-yl) methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 224. 3-Z- [1- (4 - ((3-Hydroxy-pyrrolidin-1-yl) methyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 225. 3-Z- [1- (4- (Cyclohexylylmethyl) anilino) -1-phenyl methylene] -6-ethoxycarbonyl-2-indolinone
• 226. 3-Z- [1- (4- (Cyclohexylcarbonyl) anilino) -1-phenyl methylene] -6-ethoxycarbonyl-2-indolinone
• 227. 3-Z- [1- (4-Diethylaminomethyl-anilino) -1-phenylmethyl len] -6-ethoxycarbonyl-2-indolinone  
• 228. 3-Z- [1- (4- (N- (n-Hexyl) -N-methylaminomethyl) anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 229. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N- (furan-2- carbonyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 230. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N- (2-methoxy benzoyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 231. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N- (pyridine-3- carbonyl) amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 232. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N- (phenyl-acetyl) - amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 233. 3-Z- [1- (4- (imidazol-2-yl) anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 234. 3-Z- [1- (4- (1-ethylimidazol-2-yl) anilino) -1-phenyl- methylene] -6-ethoxycarbonyl-2-indolinone
• 235. 3-Z- [1- (4- (1-benzylimidazol-2-yl) anilino) -1-phenyl- methylene] -6-ethoxycarbonyl-2-indolinone
• 236. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N- isopropylsulfonylamino) anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 237. 3-Z- [1- (4- (N - ((4-Benzylpiperazin-1-yl) methylcarbonyl) - N-methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone  
• 238. 3-Z- [1- (4- (N- (Pyrrolidin-1-yl-methylcarbonyl) -N-methyl amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 239. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-acetylamino) -3- bromo-anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 240. 3-Z- [1- (4- (5-methylimidazol-4-yl) anilino) -1-phenyl- methylene] -6-ethoxycarbonyl-2-indolinone
• 241. 3-Z- [1- (4- (N - ((2-Dimethylaminoethyl) carbonyl) -N- isopropylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 242. 3-Z- [1- (4- (N - ((2-Dimethylaminoethyl) carbonyl) -N- benzylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 243. 3-Z- [1- (4- (N-butyl-N-tert.butoxycarbonylaminomethyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 244. 3-Z- [1- (4- (N - ((N-aminocarbonylmethyl-N-methylamino) - methylcarbonyl) -N-methyl-amino) -anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 245. 3-Z- [1- (4- (N - ((N-benzyl-N-methylamino) methylcarbonyl) - N-methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 246. 3-Z- [1- (4- (N- (Di- (2-methoxyethyl) amino-methylcarbonyl) - N-methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 247. 3-Z- [1- (4- (N - ((2- (4-tert-butoxycarbonyl-piperazin-1-yl) - ethyl) carbonyl) -N-methylamino) anilino) -1-phenylmethylene] - 6-ethoxycarbonyl-2-indolinone  
• 248. 3-Z- [1- (4- (N - ((2- (piperidin-1-yl) ethyl) carbonyl) -N- methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 249. 3-Z- [1- (4- (N - ((2- (N-benzyl-N-methylamino) ethyl) - carbonyl) -N-methylamino) anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 250. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-isopropyl amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 251. 3-Z- [1- (4- (N- (Piperidin-1-yl-methylcarbonyl) -N- isopropylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 252. 3-Z- [1- (4- (N - ((4-tert-butoxycarbonyl-piperazin - 1-yl) - methylcarbonyl) -N-isopropyl-amino) -anilino) -1-phenyl-methy len] -6-ethoxycarbonyl-2-indolinone
• 253. 3-Z- [1- (4- (N - ((N-Benzyl-N-methylamino) methylcarbonyl) - N-benzylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 254. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-benzyl- amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 255. 3-Z- [1- (4- (N- (Piperidin-1-yl-methylcarbonyl) -N-benzyl- amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 256. 3-Z- [1- (4- (1,2,4-Triazol-2-ylmethyl) anilino) -1-phenyl- methylene] -6-ethoxycarbonyl-2-indolinone
• 257. 3-Z- [1- (4- (1,2,3-Triazol-2-ylmethyl) anilino) -1-phenyl- methylene] -6-ethoxycarbonyl-2-indolinone  
• 258. 3-Z- [1- (4- (1,2,3-Triazol-1-ylmethyl) anilino) -1-phenyl methylene] -6-ethoxycarbonyl-2-indolinone
• 259. 3-Z- [1- (4 - ((N-aminocarbonylmethyl-N-methylamino) - methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 260. 3-Z- [1- (4 - ((di- (2-methoxyethyl) amino) methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 261. 3-Z- [1- (4 - ((Di- (2-hydroxyethyl) amino) methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 262. 3-Z- [1- (4 - ((N-ethoxycarbonylmethyl-N-methylamino) - methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 263. 3-Z- [1- (4- (Azetidin-1-ylmethyl) anilino) -1-phenyl- methylene] -6-ethoxycarbonyl-2-indolinone
• 264. 3-Z- [1- (4- (N-Propyl-N-tert-butoxycarbonylaminomethyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 265. 3-Z- [1- (4 - ((N- (2- (2-methoxyethoxy) ethyl) -N-methyl- amino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 266. 3-Z- [1- (4 - ((N- (tert-butoxycarbonyl-3-aminopropyl) -N- methylamino) methyl) anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 267. 3-Z- [1- (4 - ((N- (Methylcarbamoyl-methyl) -N-methyl-amino) - methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon  
• 268. 3-Z- [1- (4 - ((N- (Dimethylcarbamoyl-methyl) -N-methyl- amino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 269. 3-Z- [1- (4 - ((N-Propyl-N-methylamino) methyl) anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 270. 3-Z- [1- (4 - ((N- (2-Dimethylaminoethyl) -N-methylamino) - methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 271. 3-Z- [1- (4 - ((N- (3-Dimethylamino-propyl) -N-methylamino) - methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 272. 3-Z- [1- (4 - ((N- (2-methoxyethyl) -N-methylamino) methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 273. 3-Z- [1- (4 - ((N- (2-Hydroxyethyl) -N-methylamino) methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 274. 3-Z- [1- (4 - ((N- (Dioxolan-2-yl-methyl) -N-methyl-amino) - methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 275. 3-Z- [1- (4- (3-oxopiperazin-1-ylmethyl) anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 276. 3-Z- [1- (4- (N- (piperazin-1-yl-methylcarbonyl) -N- isopropylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 277. 3-Z- [1- (4- (N - ((2- (piperazin-1-yl) ethyl) carbonyl) -N- methylamino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone  
• 278. 3-Z- [1- (4 - ((N- (3-aminopropyl) -N-methylamino) methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 279. 3-Z- [1- (4- (N- (3-Methylamino-propyl) -N-methylsulfonyl- amino) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 280. 3-Z- [1- (4-ureidomethyl anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 281. 3-Z- [1- (4-guanidinomethyl anilino) -1-phenylmethylene] -6- ethoxycarbonyl-2-indolinone
• 282. 3-Z- [1- (4- (N-methylsulfonylaminomethyl) anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 283. 3-Z- [1- (4- (4-Benzoyl-piperazin-1-yl-methyl) -anilino) -1- phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 284. 3-Z- [1- (4 - ((N- (3-acetylamino-propyl) -N-methylamino) - methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-in dolinon
• 285. 3-Z- [1- (4 - ((N- (3-Methylsulfonylamino-propyl) -N-methyl- amino) methyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl- 2-indolinone
• 286. 3-Z- [1- (4 - ((N-carboxymethyl-N-methylamino) methyl) - anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone
• 287. 3-Z- (1-anilino-1-phenylmethylene) -6-methoxycarbonyl-2-in dolinon
• 288. 3-Z- [1- (4-nitro-anilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone  
• 289. 3-Z- [1- (4-fluoro-anilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone
• 290. 3-Z- [1- (4-chloroanilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone
• 291. 3-Z- [1- (4-bromoanilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone
• 292. 3-Z- [1- (4-iodo-anilino) -1-phenylmethylene] -6-methoxycar bonyl-2-indolinone
• 293. 3-Z- [1- (4-cyanoanilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone
• 294. 3-Z- [1- (4-carboxy-anilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone
• 295. 3-Z- [1- (4-methoxy-anilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone
• 296. 3-Z- [1- (4-ethoxy-anilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone
• 297. 3-Z- [1- (4-trifluoromethyl-anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone
• 298. 3-Z- [1- (4-methylmercapto-anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone
• 299. 3-Z- [1- (4- (isopropylaminomethyl) anilino) -1-phenyl-me ethylene] -6-methoxycarbonyl-2-indolinone
• 300. 3-Z- [1- (4- (anilinomethyl) anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone  
• 301. 3-Z- [1- (4- (isobutylaminomethyl) anilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone
• 302. 3-Z- [1- (4- (Cyclohexylaminomethyl) anilino) -1-phenyl-me ethylene] -6-methoxycarbonyl-2-indolinone
• 303. 3-Z- [1- (4- (Benzylaminomethyl) anilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone
• 304. 3-Z- [1- (4 - ((N-Methyl-N-propylamino) methyl) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 305. 3-Z- [1- (4 - ((N-isopropyl-N-methylamino) methyl) anili no) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 306. 3-Z- [1- (4 - ((N-ethyl-N-propylamino) methyl) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 307. 3-Z- [1- (4 - ((N-ethyl-N-isopropylamino) methyl) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 308. 3-Z- [1- (4- (Dipropylaminomethyl) anilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone
• 309. 3-Z- [1- (4- (diisopropylaminomethyl) anilino) -1-phenylme ethylene] -6-methoxycarbonyl-2-indolinone
• 310. 3-Z- [1- (4 - ((N-Benzyl-N-ethylamino) methyl) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 311. 3-Z- [1- (4- (Dibenzylaminomethyl) anilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone
• 312. 3-Z- [1- (4- (3,6-Dihydro-2H-pyridin-1-ylmethyl) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone  
• 313. 3-Z- [1- (4- (3,5-Dimethylpiperidin-1-ylmethyl) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 314. 3-Z- [1- (4- (azepan-1-ylmethyl) anilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone
• 315. 3-Z- [1- (4- (2-aminoethyl) anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone
• 316. 3-Z- [1- (4- (2-Methylaminoethyl) anilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone
• 317. 3-Z- [1- (4- (2-Ethylaminoethyl) anilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone
• 318. 3-Z- [1- (4- (2-Dimethylaminoethyl) anilino) -1-phenylme ethylene] -6-methoxycarbonyl-2-indolinone
• 319. 3-Z- [1- (4- (2-Diethylaminoethyl) anilino) -1-phenylme ethylene] -6-methoxycarbonyl-2-indolinone
• 320. 3-Z- [1- (4- (2-piperidin-1-yl-ethyl) anilino) -1-phenyl-me ethylene] -6-methoxycarbonyl-2-indolinone
• 321. 3-Z- [1- (4- (2-acetylaminoethyl) anilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone
• 322. 3-Z- [1- (4- (3-aminopropyl) anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone
• 323. 3-Z- [1- (4- (3-Dimethylamino-propyl) anilino) -1-phenyl-me ethylene] -6-methoxycarbonyl-2-indolinone
• 324. 3-Z- [1- (4- (N-aminomethylcarbonyl-N-methyl-amino) -anili no) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone  
• 325. 3-Z- [1- (4- (N-ethylaminomethylcarbonyl-N-methylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 326. 3-Z- [1- (4- (N-diethylaminomethylcarbonyl-N-methylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 327. 3-Z- [1- (4- (N-dipropylaminomethylcarbonyl-N-methyl- amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
• 328. 3-Z- [1- (4- (N - ((N-ethyl-N-methylamino) methylcarbonyl) - N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 329. 3-Z- [1- (4- (N - ((N-ethyl-N-propylamino) methylcarbonyl) - N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 330. 3-Z- [1- (4- (N - ((N-methyl-N-propylamino) methylcarbonyl) - N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 331. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-ethylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 332. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-propyl-ami no) -anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 333. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-butyl-amino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 334. 3-Z- [1- (4- (N- (2-Aminoethylcarbonyl) -N-methylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 335. 3-Z- [1- (4- (N- (2-Diethylaminoethylcarbonyl) -N-methyl- amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indo linon  
• 336. 3-Z- [1- (4- (N-acetyl-N- (2-aminoethyl) amino) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 337. 3-Z- [1- (4- (N-Acetyl-N- (2-methylamino-ethyl) amino) -ani lino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 338. 3-Z- [1- (4- (N-acetyl-N- (3-methylamino-propyl) amino) -ani lino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 339. 3-Z- [1- (4- (N-acetyl-N- (2-piperidin-1-yl-ethyl) amino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 340. 3-Z- [1- (4- (N-Acetyl-N- (aminocarbonylmethyl) amino) -ani lino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 341. 3-Z- [1- (4- (N-acetyl-N- (piperidin-1-yl-carbonylmethyl) - amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indo linon
• 342. 3-Z- [1- (4- (N-methyl-N- (aminocarbonyl) amino) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 343. 3-Z- [1- (4- (N-Methyl-N- (methylaminocarbonyl) amino) -ani lino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 344. 3-Z- [1- (4- (N-methyl-N- (dimethylaminocarbonyl) amino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 345. 3-Z- [1- (4- (N-methyl-N- (piperidin-1-ylcarbonyl) amino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 346. 3-Z- [1- (4- (N- (2-Ethylamino-ethyl) -N-methylsulfonyl-a 23656 00070 552 001000280000000200012000285912354500040 0002010042696 00004 23537mi no) -anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone  
• 347. 3-Z- [1- (4- (N- (2-Diethylamino-ethyl) -N-methylsulfonyl- amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indo linon
• 348. 3-Z- [1- (4- (N- (2-Pyrrolidin-1-yl-ethyl) -N-methylsulfonyl- amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indo linon
• 349. 3-Z- [1- (4- (N- (2-Piperidin-1-yl-ethyl) -N-methylsulfonyl- amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indo linon
• 350. 3-Z- [1- (4- (N- (2-Piperazin-1-yl-ethyl) -N-methylsulfonyl- amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indo linon
• 351. 3-Z- [1- (4- (N- (2- (4-Morpholin-1-yl) ethyl) -N-methylsul fonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 352. 3-Z- [1- (4- (N- (Ethylaminocarbonylmethyl) -N-methylsulfo nylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-in dolinon
• 353. 3-Z- [1- (4- (N- (Diethylaminocarbonylmethyl) -N-methylsul fonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 354. 3-Z- [1- (4- (N- (Pyrrolidin-1-ylcarbonylmethyl) -N-methyl sulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 355. 3-Z- [1- (4- (N- (Piperidin-1-ylcarbonylmethyl) -N-methyl sulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone  
• 356. 3-Z- [1- (4- (N- (Piperazin-1-ylcarbonylmethyl) -N-methyl sulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 357. 3-Z- [1- (4- (N - ((Morpholin-4-yl) carbonylmethyl) -N-methyl sulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 358. 3-Z- [1- (4- (2-Dimethylaminoethoxy) anilino) -1-phenylme ethylene] -6-methoxycarbonyl-2-indolinone
• 359. 3-Z- [1- (4- (3-Dimethylamino-propoxy) anilino) -1-phenyl methylene] -6-methoxycarbonyl-2-indolinone
• 360. 3-Z- [1- (4- (aminocarbonylmethyl) anilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone
• 361. 3-Z- [1- (4- (2-aminocarbonylethyl) anilino) -1-phenylme ethylene] -6-methoxycarbonyl-2-indolinone
• 362. 3-Z- [1- (4- (pyridin-2-yl) anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone
• 363. 3-Z- [1- (4- (pyridin-3-yl) anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone
• 364. 3-Z- [1- (4 ((N-phenethyl-N-methylamino) methyl) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 365. 3-Z- [1- (4- (N-acetyl-N-methylamino) anilino) -1-phenyl methylene] -6-methoxycarbonyl-2-indolinone
• 366. 3-Z- [1- (4- (N-Ethylcarbonyl-N- (dimethylaminocarbonylme thyl) amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone  
• 367. 3-Z- [1- (4- (N-methyl-N-methylsulfonylamino) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 368. 3-Z- [1- (4-carboxymethyl-anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
• 369. 3-Z- [1- (4-carbamoylmethyl anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
• 370. 3-Z- [1- (4-Dimethylcarbamoylmethylanilino) -1-phenyl methylene] -6-methoxycarbonyl-2-indolinone
• 371. 3-Z- [1- (4-tetrazol-5-yl-anilino) -1-phenylmethylene] - 6-methoxycarbonyl-2-indolinone
• 372. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) methylene] - 6-methoxycarbonyl-2-indolinone
• 373. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) ethylidene] - 6-methoxycarbonyl-2-indolinone
• 374. 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) propylidene] - 6-methoxycarbonyl-2-indolinone
• 375. 3-Z- [1- (4- (piperidin-1-y1-methyl) anilino) butylidene] - 6-methoxycarbonyl-2-indolinone
• 376. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) - anilino) methylene] -6-methoxycarbonyl-2-indolinone
• 377. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) - anilino) ethylidene] -6-methoxycarbonyl-2-indolinone
• 378. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) - anilino) propylidene] -6-methoxycarbonyl-2-indolinone  
• 379. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) - anilino) butylidene] -6-methoxycarbonyl-2-indolinone
• 380. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonyl- amino) anilino) methylene] -6-methoxycarbonyl-2-indolinone
• 381. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonyl- amino) anilino) ethylidene] -6-methoxycarbonyl-2-indolinone
• 382. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonyl- amino) anilino) propylidene] -6-methoxycarbonyl-2-indolinone
• 383. 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonyl- amino) anilino) butylidene] -6-methoxycarbonyl-2-indolinone
• 384. 3-Z- [1- (4-tetrazol-5-yl-anilino) methylene] -6-methoxy carbonyl-2-indolinone
• 385. 3-Z- [1- (4-Tetrazol-5-yl-anilino) ethylidene] -6-methoxy carbonyl-2-indolinone
• 386. 3-Z- [1- (4-tetrazol-5-yl-anilino) propylidene] -6-methoxy carbonyl-2-indolinone
• 387. 3-Z- [1- (4-tetrazol-5-yl-anilino) butylidene] -6-methoxy carbonyl-2-indolinone
• 388. 3-Z- [1- (4-carboxy-anilino) -methylene] -6-methoxycarbonyl- 2-indolinone
• 389. 3-Z- [1- (4-carboxy-anilino) ethylidene] -6-methoxycarbonyl- 2-indolinone
• 390. 3-Z- [1- (4-carboxy-anilino) propylidene] -6-methoxycarbo nyl-2-indolinone  
• 391. 3-Z- [1- (4-carboxy-anilino) butylidene] -6-methoxycarbonyl- 2-indolinone
• 392. 3-Z- [1- (4- (N-benzyl-N-methylaminomethyl) anilino) -1-me ethyl methylene] -6-methoxycarbonyl-2-indolinone
• 393. 3-Z- [1- (4- (2,3,4,5-tetrahydro-benzo (d) azepin-3-yl-me thyl) anilino) -1-methyl-methylene] -6-methoxycarbonyl-2-in dolinon
• 394. 3-Z- [1- (4 - ((Benzo (1,3) dioxol-5-ylmethyl) methylamino methyl) anilino) -1-methyl-methylene] -6-methoxycarbonyl-2-in dolinon
• 395. 3-Z- [1- (4- (N-phenethyl-N-methylaminomethyl) anilino) -1- methyl methylene] -6-methoxycarbonyl-2-indolinone
• 396. 3-Z- [1- (4- (N- (3,4-Dimethoxybenzyl) -N-methylamino methyl) anilino) -1-methyl-methylene] -6-methoxycarbonyl-2-in dolinon
• 397. 3-Z- [1- (4- (N- (4-Chloro-benzyl) -N-methylamino-methyl) - anilino) -1-methyl-methylene] -6-methoxycarbonyl-2-indolinone
• 398. 3-Z- [1- (4- (N- (4-Methylbenzyl) -N-methylamino-methyl) - anilino) -1-methyl-methylene] -6-methoxycarbonyl-2-indolinone
• 399. 3-Z- [1- (4- (N- (4-Fluoro-benzyl) -N-methylamino-methyl) - anilino) -1-methyl-methylene] -6-methoxycarbonyl-2-indolinone
• 400. 3-Z- [1- (4- (N- (4-Bromo-benzyl) -N-methylamino-methyl) - anilino) -1-methyl-methylene] -6-methoxycarbonyl-2-indolinone
• 401. 3-Z- [1- (4- (N- (3-Dimethylamino-propionyl) -N- dimethylaminocarbonylmethylamino) anilino) -1-phenyl methylene] -6-methoxycarbonyl-2-indolinone  
• 402. 3-Z- [1- (4- (N- (4-Dimethylamino-butyryl) -N- dimethylaminocarbonylmethylamino) anilino) -1-phenyl- methylene] -6-methoxycarbonyl-2-indolinone
• 403. 3-Z- [1- (4- (N-Dimethylaminocarbonylmethyl-N- (2- dimethylamino-ethylsulfonyl) -amino) -anilino) -1-phenyl- methylene] -6-methoxycarbonyl-2-indolinone
• 404. 3-Z- [1- (4- (N-Dimethylaminocarbonylmethyl-N- (3- dimethylamino-propylsulfonyl) amino) anilino) -1-phenyl- methylene] -6-methoxycarbonyl-2-indolinone
• 405. 3-Z- [1- (4 - ((2-Hydroxyethyl) amino methyl) anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 406. 3-Z- [1- (4 - ((2-methoxyethyl) amino methyl) anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 407. 3-Z- [1- (4 - ((2-Dimethylamino-ethyl) -amino-methyl) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 408. 3-Z- [1- (4 - ((3-Dimethylamino-propyl) -amino-methyl) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 409. 3-Z- [1- (4 - ((N-tert-butoxycarbonyl-2-amino-ethyl) -amino- methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
• 410. 3-Z- [1- (4 - ((N-tert-butoxycarbonyl-3-aminopropyl) amino- methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indo linon
• 411. 3-Z- [1- (4 - ((2-Amino-ethyl) -amino-methyl) -anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 412. 3-Z- [1- (4 - ((3-Amino-propyl) -amino-methyl) -anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone  
• 413. 3-Z- [1- (4 - ((2-acetylamino-ethyl) amino-methyl) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 414. 3-Z- [1- (4 - ((3-acetylamino-propyl) -amino-methyl) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 415. 3-Z- [1- (4 - ((2-Methylsulfonylamino-ethyl) -amino-methyl) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 416. 3-Z- [1- (4 - ((3-Methylsulfonylamino-propyl) amino-methyl) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 417. 3-Z- [1- (4- (N- (N-tert-Butoxycarbonyl-2-amino-ethyl) -N- methylamino methyl) anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
• 418. 3-Z- [1- (4- (N- (2-Aminoethyl) -N-methylamino-methyl) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 419. 3-Z- [1- (4- (N- (2-Acetylamino-ethyl) -N-methylamino- methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
• 420. 3-Z- [1- (4- (N- (2-Methylsulfonylamino-ethyl) -N-methyl- aminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
• 421. 3-Z- [1- (4- (carboxymethylaminomethyl) anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 422. 3-Z- [1- (4- (Ethoxycarbonylmethylaminomethyl) anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 423. 3-Z- [1- (4- (carbamoylmethylamino-methyl) anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone  
• 424. 3-Z- [1- (4- (dimethylcarbamoyl-methylamino-methyl) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 425. 3-Z- [1- (4- (methylcarbamoyl-methylamino-methyl) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 426. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-amino-anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 427. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-nitro-anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 428. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-acetylamino-anilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone
• 429. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-methylsulfonylamino-anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
• 430. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-cyano-anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 431. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-hydroxy-anilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone
• 432. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-methoxy-anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
• 433. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-ethoxycarbonyl-anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone  
• 434. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-carboxy-anilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone
• 435. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-carbamoyl-anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
• 436. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-chloro-anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 437. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-fluoro-anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 438. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-bromo-anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
• 439. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-methyl-anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 440. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3-trifluoromethyl-anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
• 441. 3-Z- [1- (4- (N-dimethylaminomethylcarbonyl-N-methyl- amino) -3, 5-dibromo-anilino) -1-phenylmethylene] -6-methoxy carbonyl-2-indolinone
• 442. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) -3,5-dichloro-anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone  
• 443. 3-Z- [1- (4- (Dimethylaminomethyll-3-amino-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 444. 3-Z- [1- (4- (Dimethylaminomethyl) -3-nitro-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 445. 3-Z- [1- (4- (Dimethylaminomethyl) -3-acetylamino-anilino) - 1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 446. 3-Z- [1- (4- (dimethylaminomethyl) -3-methylsulfonylamino- anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 447. 3-Z- [1- (4- (dimethylaminomethyl) -3-cyano-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 448. 3-Z- [1- (4- (Dimethylaminomethyl) -3-hydroxy-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 449. 3-Z- [1- (4- (Dimethylaminomethyl) -3-methoxy-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 450. 3-Z- [1- (4- (dimethylaminomethyl) -3-ethoxycarbonyl- anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 451. 3-Z- [1- (4- (Dimethylaminomethyl) -3-carboxy-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 452. 3-Z- [1- (4- (Dimethylaminomethyl) -3-carbamoyl-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 453. 3-Z- [1- (4- (Dimethylaminomethyl) -3-chloro-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 454. 3-Z- [1- (4- (Dimethylaminomethyl) -3-fluoro-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone  
• 455. 3-Z- [1- (4- (Dimethylaminomethyl) -3-bromo-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 456. 3-Z- [1- (4- (Dimethylaminomethyl) -3-methyl-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 457. 3-Z- [1- (4- (dimethylaminomethyl) -3-trifluoromethyl- anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 458. 3-Z- [1- (4-dimethylaminomethyl-3,5-dibromo-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 459. 3-Z- [1- (4- (Dimethylaminomethyl) -3,5-dichloro-anilino) -1- phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 460. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) -1-phenylmethyl len] -6 - [(2-hydroxy-ethoxy) carbonyl] -2-indolinone
• 461. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) -1-phenylmethyl len] -6 - [(ethoxycarbonyl-methoxy) carbonyl] -2-indolinone
• 462. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) -1-phenylmethyl len] -6 - [(carboxymethoxy) carbonyl] -2-indolinone
• 463. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) -1-phenylmethyl len] -6 - [(carbamoyl-methoxy) carbonyl] -2-indolinone
• 464. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) anilino) -1-phenylmethylene] -6 - [(2-hydroxy-ethoxy) - carbonyl] -2-indolinone
• 465. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl amino) anilino) -1-phenylmethylene] -6 - [(ethoxycarbonyl- methoxy) carbonyl] -2-indolinone  
• 466. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) anilino) -1-phenylmethylene] -6 - [(carboxymethoxy) - carbonyl] -2-indolinone
• 467. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) anilino) -1-phenylmethylene] -6 - [(carbamoyl-methoxy) - carbonyl] -2-indolinone
• 468. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) anilino) -1-phenylmethylene] -6 - [(2-methoxyethoxy) - carbonyl] -2-indolinone
• 469. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) anilino) -1-phenylmethylene] -6 - [(2-dimethylamino ethoxy) carbonyl] -2-indolinone
• 470. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) anilino) -1-phenylmethylene] -6 - [(2- (N- tert-butoxycarbonylamino) ethoxy) carbonyl] -2-indolinone
• 471. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) anilino) -1-phenylmethylene] -6 - [(2-aminoethoxy) - carbonyl) -2-indolinone
• 472. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl- amino) anilino) -1-phenylmethylene] -6 - [(2,2,2-trifluoroethoxy) - carbonyl] -2-indolinone
• 473. 3-Z- [1- (4- (N - ((4-methylpiperazin-1-yl) methylcarbonyl) - N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl- 2-indolinone
• 474. 3-Z- [1- (4- (N- (imidazo-1-yl-methylcarbonyl) -N-methyl- amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone  
• 475. 3-Z- [1- (4- (N- (Phthalimido-2-yl-methylcarbonyl) -N-methyl- amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indo linon
• 476. 3-Z- [1- (4- (N-aminomethylcarbonyl-N-methylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 477. 3-Z- [1- (4- (N-acetylaminomethylcarbonyl-N-methylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 478. 3-Z- [1- (4- (N-methylsulfonylaminomethylcarbonyl-N-methyl- amino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indolinone
• 479. 3-Z- [1- (4- (N - ((N- (2-methoxyethyl) -N-methylamino) - methylcarbonyl) -N-methyl-amino) -anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
• 480. 3-Z- (1- (4- (N - ((N- (2-dimethylaminoethyl) -N-methylamino)) methylcarbonyl) -N-methyl-amino) -anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
• 481. 3-Z- [1- (4- (N - ((di- (2-hydroxyethyl) amino) - methylcarbonyl) -N-methyl-amino) -anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
• 482. 3-Z- [1- (4-tert-butoxycarbonylmethyl-anilino) -1-phenyl- methylene] -6-methoxycarbonyl-2-indolinone
• 483. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl-ami no) -anilino) -methylene] -6-methoxycarbonyl-2-indolinone
• 484. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl-ami no) anilino) ethylidene] -6-methoxycarbonyl-2-indolinone
• 485. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl-ami no) -anilino) -propylidene] -6-methoxycarbonyl-2-indolinone  
• 486. 3-Z- [1- (4- (N-Dimethylaminomethylcarbonyl-N-methyl-ami no) -anilino) -butylidene] -6-methoxycarbonyl-2-indolinone
• 487. 3-Z- [1- (4- (dimethylaminomethyl) anilino) methylene] -6- methoxycarbonyl-2-indolinone
• 488. 3-Z- [1- (4- (Dimethylaminomethyl) anilino) ethylidene] -6- methoxycarbonyl-2-indolinone
• 489. 3-Z- [1- (4- (dimethylaminomethyl) anilino) propylidene] -6- methoxycarbonyl-2-indolinone
• 490. 3-Z- [1- (4- (dimethylaminomethyl) anilino) butylidene] -6- methoxycarbonyl-2-indolinone
• 491. 3-Z- [1- (4-tert-butyloxycarbonylanilino) -1-phenylmethyl len] -6-methoxycarbonyl-2-indolinone
• 492. 3-Z- [1- (4- (N- (2-Dimethylaminoethyl) -N-methylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 493. 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-methylamino) - anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone
• 494. 3-Z- [1- (4- (N-methyl-acetylamino) anilino) -1-phenyl- methylene] -6-methoxycarbonyl-2-indolinone
• 495. 3-Z- [1- (4- (imidazol-4-yl) anilino) -1-phenylmethylene] -6- methoxycarbonyl-2-indolinone
• 496. 3-Z- [1- (4 - ((N- (Dioxolan-2-yl-methyl) -N-methyl-amino) - methyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-in dolinon
• 497. 3-Z- [1- (4- (N-benzyl-N-methylamino-methyl) anilino) -1- methyl methylene] -6-carbamoyl-2-indolinone  
• 498. 3-Z- [1- (4- (2,3,4,5-tetrahydro-benzo (d) azepin-3-yl-me thyl) anilino) -1-methyl-methylene] -6-carbamoyl-2-indolinone
• 499. 3-Z- [1- (4 - ((Benzo (1,3) dioxol-5-ylmethyl) methylamino- methyl) anilino) -1-methyl-methylene] -6-carbamoyl-2-indolinone
• 500. 3-Z- [1- (4- (N-phenethyl-N-methylamino-methyl) anilino) - 1-methyl-methylene] -6-carbamoyl-2-indolinone
• 501. 3-Z- [1- (4- (N- (3,4-Dimethoxybenzyl) -N-methylamino- methyl) anilino) -1-methyl-methylene] -6-carbamoyl-2-indolinone
• 502. 3-Z- [1- (4- (N- (4-Chloro-benzyl) -N-methylamino-methyl) - anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone
• 503. 3-Z- [1- (4- (N- (4-Methylbenzyl) -N-methylamino-methyl) - anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone
• 504. 3-Z- [1- (4- (N- (4-Fluoro-benzyl) -N-methylamino-methyl) - anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone
• 505. -Z- [1- (4- (N- (4-bromo-benzyl) -N-methylamino-methyl) - anilino) -1-methylmethylene] -6-carbamoyl-2-indolinone

Example 13 Dry ampoule with 75 mg active ingredient per 10 ml composition

Active ingredient 75.0 mg Mannitol 50.0 mg Water for injections ad 10.0 ml

Manufacturing

Active ingredient and mannitol are dissolved in water. After bottling is freeze-dried. The resolution for ready to use Solution is done with water for injections.

Example 14 Dry ampoule with 35 mg of active ingredient per 2 ml composition

Active ingredient 35.0 mg Mannitol 100.0 mg Water for injections ad 2.0 ml

Manufacturing

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

The ready-to-use solution is dissolved with water for injections.

Example 15 Tablet with 50 mg of active ingredient composition

(1) Active ingredient 50.0 mg (2) milk sugar 98.0 mg (3) corn starch 50.0 mg (4) polyvinyl pyrrolidone 15.0 mg (5) Magnesium stearate 2.0 mg           215.0 mg         

Manufacturing

(1), (2) and (3) are mixed and granulated with an aqueous solution of (4). The dried granules are mixed (5). Tablets are pressed from this mixture, biplan with facets on both sides and partial notch on one side.
Tablet diameter: 9 mm.

Example 16 Tablet with 350 mg of active ingredient composition

(1) Active ingredient 350.0 mg (2) milk sugar 136.0 mg (3) corn starch 80.0 mg (4) polyvinyl pyrrolidone 30.0 mg (5) Magnesium stearate 4.0 mg           600.0 mg         

Manufacturing

(1), (2) and (3) are mixed and granulated with an aqueous solution of (4). The dried granules are mixed (5). Tablets are pressed from this mixture, biplan with facets on both sides and partial notch on one side.
Tablet diameter: 12 mm.

Example 17 Capsules with 50 mg of active ingredient composition

(1) Active ingredient 50.0 mg (2) Dried corn starch 58.0 mg (3) powdered milk sugar 50.0 mg (4) Magnesium stearate 2.0 mg           160.0 mg         

Manufacturing

(1) is triturated with (3). This trituration becomes the mixture from (2) and (4) added with intensive mixing.

This powder mixture is in a capsule filling machine Bottled hard gelatin capsules size 3.

Example 18 Capsules with 350 mg of active ingredient composition

(1) Active ingredient 350.0 mg (2) Dried corn starch 46.0 mg (3) powdered milk sugar 30.0 mg (4) Magnesium stearate 4.0 mg           430.0 mg         

Manufacturing

(1) is triturated with (3). This trituration becomes the mixture from (2) and (4) added with intensive mixing.

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

Example 19 Suppositories with 100 mg of active ingredient Contains 1 suppository

Active ingredient 100.0 mg Polyethylene glycol (M.G. 1500) 600.0 mg Polyethylene glycol (M.G. 6000) 460.0 mg Polyethylene sorbitan monostearate 840.0 mg           2,000.0 mg         

Manufacturing

The polyethylene glycol is used together with polyethylene sorbitan mo melted nostearate. At 40 ° C the ground active substance punch homogeneously dispersed in the melt. It gets to 38 ° C cooled and into weakly pre-cooled suppository forms poured.

Claims (10)

1. Indolinones of the general formula substituted in the 6-position
in the
X is an oxygen or sulfur atom,
R _{1 is} a hydrogen atom or a prodrug residue,
R _{2 is} a carboxy group, a linear or branched C _1-6 alkoxy-carbonyl group, a C _4-7 cycloalkoxycarbonyl or an aryloxycarbonyl group,
a linear or branched C _1-6 -alkoxy-carbonyl group which is terminated in the alkyl part by a phenyl, heteroaryl, carboxy, C _1-3 -alkoxy-carbonyl, aminocarbonyl, C _1-3 -alkylamino-carbonyl- or di (C _1-3 alkyl) aminocarbonyl group is substituted,
a linear or branched C _2-6 alkoxy carbonyl group which is terminated in the alkyl part by a chlorine atom or a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _{1- 3} alkyl) amino group is substituted,
an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group optionally substituted in the 2-position of the ethyl group by a hydroxy or C _1-3 alkoxy group, or
if R _{4 is} not an aminosulfonyl-phenyl or N- (C _1-5 -alkyl) - C _1-3 -alkylaminocarbonyl-phenyl group, also a di- (C _1-2 -alkyl) -aminocarbonyl group,
R _{3 is} a hydrogen atom, a C _1-6 alkyl, C _3-7 cycloalkyl, trifluoromethyl or heteroaryl group,
a phenyl or naphthyl group, one by a fluorine, chlorine, bromine or iodine atom, by a trifluoromethyl, C _1-3 alkyl or C _1-3 alkoxy group mono- or disubstituted phenyl or naphthyl group, in which In the case of disubstitution, the substituents may be the same or different and where the unsubstituted as well as the mono- and disubstituted phenyl and naphthyl groups mentioned above
by a hydroxy, hydroxyC _1-3 alkyl or C _1-3 alkoxyC _1-3 alkyl group,
by a cyano, carboxy, carboxyC _1-3 alkyl, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino carbonyl or di (C _1-3 alkyl) aminocarbonyl group ,
through a nitro group,
by an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or amino C _1-3 alkyl group,
by a C _1-3 alkylcarbonylamino, N- (C _1-3 alkyl) -C _1-3 alkyl kylcarbonylamino, C _1-3 alkylcarbonylamino C _1-3 alkyl, N- (C _{1 -3-} alkyl) -C _1-3 -alkylcarbonylamino-C _1-3 -alkyl-, C _1-3 -alkyl sulfonylamino-, C _1-3 -alkylsulfonylamino-C _1-3 -alkyl-, N- (C _{1 -3-} alkyl) -C _1-3 -alkylsulfonylamino-C _1-3 -alkyl- or aryl-C _1-3 -alkylsulfonylamino group,
by a Cycloalkylamino-, Cycloalkylenimino-, Cycloalkyleniminocarbonyl-, Cycloalkylenimino-C _1-3 -alkyl-, Cycloalkyleniminocarbonyl-C _1-3 -alkyl- or Cycloalkyleniminosulfonyl-C _1-3 -alkyl group each with 4 to 7 ring, whereby each the methylene group in position 4 in a 6- or 7-membered cycloalkyleneimino group can be replaced by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH or -N (C _1-3 -alkyl) group,
or can be substituted by a heteroaryl or heteroarylC _1-3 alkyl group,
R _{4 is} a C _3-7 cycloalkyl group,
wherein the methylene group in position 4 of a 6- or 7- membered cycloalkyl group is substituted by an amino, C _1-3 -alkylamino or di- (C _1-3 -alkyl) -amino group or by an -NH- or -N (C _1-3 alkyl) group can be replaced,
or a phenyl group substituted by the group R ₆ , which is additionally substituted by fluorine, chlorine, bromine or iodine atoms, by C _1-5 alkyl, trifluoromethyl, hydroxy, C _1-3 alkoxy, carboxy, C _1-3 alkoxycarbonyl, amino, acetylamino, C _1-3 alkyl sulfonyl amino, aminocarbonyl, C _1-3 alkyl aminocarbonyl, di (C _1-3 alkyl) aminocarbonyl, aminosulfonyl, C _1-3 alkylaminosulfonyl, di (C _1-3 alkyl) aminosulfonyl, nitro or cyano groups may be mono- or disubstituted, where the substituents may be the same or different and in which
R _{6 is} a hydrogen, fluorine, chlorine, bromine or iodine atom,
a cyano, nitro, amino, C _1-5 alkyl, C _3-7 cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl group,
the group of the formula
in which the hydrogen atoms bonded to a nitrogen atom can each be replaced independently of one another by a C _1-3 alkyl group,
a C _1-3 alkoxy group, a C _1-3 alkoxy C _1-3 alkoxy, phenyl C _1-3 alkoxy, amino C _2-3 alkoxy, C _1-3 alkylamino -C _2-3 -alkoxy-, di- (C _1-3 -alkyl) -amino-C _2-3 -alkoxy-, phenyl- _1-3 -alkylamino- C _2-3 -alkoxy-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino-C _2-3 -alkoxy-, C _5-7 -cycloalkylenimino-C _2-3 -alkoxy- or C _1-3 -alkylmercapto group,
a carboxy-, C _1-4 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylamino-carbonyl-, N- (C _1-6 -alkyl) -C _1-3 -alkylaminocarbonyl-, phenyl-C _{1 -3-} alkylamino-carbonyl-, N- (C _1-3 -alkyl) -phenyl-C _1-2 -al kylamino-carbonyl-, piperazinocarbonyl or N- (C _1-3 -alkyl) -pi perazinocarbonyl group,
a C _1-3 alkylaminocarbonyl or N- (C _1-5 alkyl) -C _1-3 alkyl alkaminocarbonyl group in which an alkyl part is replaced by a carboxy or C _1-3 alkoxycarbonyl group or in 2- or 3- Position is substituted by a di- (C _1-3 alkyl) amino, piperazino, N- (C _1-3 alkyl) piperazino or a 4- to 7-membered cycloalkyleneimino group,
a C _3-7 cycloalkyl carbonyl group,
wherein the methylene group in position 4 of the 6- or 7- membered cycloalkyl part is substituted by an amino, C _1-3 -alkylamino or di- (C _1-3 -alkyl) -amino group or by an -NH- or -N (C _1-3 alkyl) group can be replaced,
a 4- to 7-membered cycloalkyleneimino group in which a methylene group linked to the imino group can be replaced by a carbonyl or sulfonyl group or
the cycloalkylene part can be condensed with a phenyl ring or
one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group or / and
each the methylene group in position 4 of a 6- or 7- membered cycloalkyleneimino group by a carboxy-, C _1-3 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocar bonyl-, di- (C _1-3 -alkyl) - aminocarbonyl, phenyl-C _1-3 alkyl amino or N- (C _1-3 alkyl) phenyl-C _1-3 alkylamino group or
through an oxygen or sulfur atom, through a sul finyl, sulfonyl, -NH,, -N (C _1-3 alkyl) -, -N (phenyl) -, -N (C _1-3 alkyl carbonyl ) - or -N (benzoyl) group can be replaced,
a C _1-4 alkyl group substituted by the group R ₇ , where
R _{7 is} a C _3-7 cycloalkyl group,
wherein the methylene group in position 4 of a 6 or 7-membered cycloalkyl group is substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or by an -NH- or -N (C _1-3 alkyl) group can be replaced or
in a 5- to 7-membered cycloalkyl group a - (CH ₂ ) ₂ group can be replaced by a -CO-NH group, a - (CH ₂ ) ₃ group by a -NH-CO-NH- or - CO-NH-CO group can be replaced or a - (CH ₂ ) ₄ group can be replaced by a -NH-CO-NH-CO group, where in each case a hydrogen atom bonded to a nitrogen atom is replaced by a C _1-3 Alkyl group can be replaced
an aryl or heteroaryl group,
a hydroxy or C _1-3 alkoxy group,
an amino, C _1-7 alkylamino, di (C _1-7 alkyl) amino, phenylamino, N-phenyl-C _1-3 -alkyl-amino-, phenyl-C _1-3 - al kylamino-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino- or di- (phenyl-C _1-3 -alkyl) -amino group,
a ω-hydroxy-C _2-3 -alkyl-amino-, N- (C _1-3 -alkyl) -ω-hy droxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _{2 -3-} alkyl) -amino-, di- (ω- (C _1-3 -alkoxy) -C _2-3 -alkyl) -amino- or N- (dioxolan-2-yl) -C _1-3 - alkyl amino group,
a C _1-3 -alkylcarbonylamino-C _2-3 -alkylamino- or C _1-3 -alkylcarbonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
a C _1-3 -alkylsulfonylamino-, N- (C _1-3 -alkyl) -C _1-3 -alkylsulfonylamino-, C _1-3 -alkylsulfonylamino-C _2-3 -alkylamino- or
C _1-3 alkylsulfonylamino-C _2-3 alkyl-N- (C _1-3 alkyl) amino group,
a hydroxycarbonyl-C _1-3 -alkylamino- or N- (C _1-3 -alkyl) -hydroxycarbonyl-C _1-3 -alkyl-amino group,
a guanidino group in which one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group,
a group of the formula
-N (R ₈ ) -CO- (CH ₂ ) _n -R ₉ (II),
in the
R _{8 is} a hydrogen atom or a C _1-3 alkyl group,
n one of the numbers 0, 1, 2 or 3 and
R _{9 is} an amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino, N- (C _1-4 alkyl) benzylamino or C _1-4 alkoxy group, a 4- to 7-membered cycloalkyleneimino group, the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group by an oxygen or Sulfur atom, by a sulfinyl, sulfonyl, -NH, -N (C _1-3 alkyl) -, -N (phenyl) -, -N (C _1-3 alkyl carbonyl) - or -N ( Benzoyl) group can be replaced, or, if n represents one of the numbers 1, 2 or 3, also represent a hydrogen atom,
a group of the formula
-N (R ₁₀ ) - (CH ₂ ) _m - (CO) _o -R ₁₁ (III),
in the
R _{10 is} a hydrogen atom, a C _1-3 alkyl group, a C _1-3 alkylcarbonyl, arylcarbonyl, phenyl C _1-3 alkylcarbonyl, C _1-3 alkylsulfonyl, arylsulfonyl or phenyl-C _1-3 alkylsulfonyl group,
m one of the numbers 1, 2, 3 or 4,
o the number 1 or, if m is one of the numbers 2, 3 or 4, also the number 0 and
R _{11 is} an amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino, N- ( C _1-4 alkyl) benzylamino, C _1-4 alkoxy or
C _1-3 -alkoxy-C _1-3 -alkoxy group, a di- (C _1-4 -alkyl) -amino-C _1-3 -alkylamino group or optionally substituted in the 1-position by a C _1-3 -alkyl group a 4- to 7-membered cycloalkyleneimino group, where the cycloalkylene part can be condensed with a phenyl ring or the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group through an oxygen or sulfur atom, through a sulfinyl, sulfonyl, -NH -, -N (C _1-3 -alkyl) -, -N (phenyl) -, -N (C _1-3 -alkyl-carbonyl) - or -N (benzoyl) - group can be replaced,
a C _4-7 cycloalkylamino, C _4-7 cycloalkyl-C _1-3 alkylamino or C _4-7 cycloalkenylamino group in which position 1 of the ring is not involved in the double bond and wherein the groups mentioned above can each additionally be substituted on the amine nitrogen atom by a C _5-7 cycloalkyl, C _2-4 alkenyl or C _1-4 alkyl group,
a 4- to 7-membered cycloalkyleneimino group in which
the cycloalkylene part with a phenyl group or with an oxazolo, imida optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, C _1-3 alkyl, C _1-3 alkoxy or amino group zolo, thiazolo, pyridino, pyrazino or pyrimidino group can be condensed or / and
one or two hydrogen atoms can each be replaced by a C _1-3 alkyl, C _5-7 cycloalkyl or phenyl group or / and
the methylene group in position 3 of a 5-membered cycloalkyleneimino group may be substituted by a hydroxy, hydroxy c _1-3 alkyl, C _1-3 alkoxy or C _1-3 alkoxy-C _1-3 alkyl group can, in each case the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group by a hydroxy, hydroxy-C _1-3 -alkyl-, C _1-3 -alkoxy-, C _1-3 -alkoxy-C _{1 -3-} alkyl-, carboxy-, C _1-4 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocarbonyl-, di- (C _1-3 -alkyl) -aminocarbonyl-, phenyl-C _1-3 - alkylamino or N- (C _1-3 alkyl) phenyl-C _1-3 alkylamino group substituted or
by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 alkyl -) -, -N (phenyl) -, -N (phenyl-C _1-3 alkyl) -) -, -N (C _1-3 -Alkyl-carbonyl -) -, -N (C _1-4 -hydroxycarbonyl -) -, -N (C _1-4 -alkoxy-carbonyl -) -, -N (Benzoyl -) - or -N (phenyl-C _1-3 alkylcarbonyl -) - group can be replaced,
where a methylene group linked to an imino nitrogen atom of the cycloalkyleneimino group can be replaced by a carbonyl or sulfonyl group or in a 5- to 7-membered monocyclic or fused to a phenyl group cycloalkyleneimino group both methylene groups linked to the imino nitrogen atom by one each Carbonyl group can be replaced
means
or R _{6 is} a C _1-4 alkyl group through a carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _1-3 alkyl) aminocarbonyl group or through a 4- to 7-membered cycloalkyleneiminocarbonyl group is substituted,
an N- (C _1-3 -alkyl) -C _2-4 -alkanoylamino group which is additionally substituted in the alkyl part by a carboxy or C _1-3 -alkoxycarbonyl group,
a group of the formula
-N (R ₁₂ ) -CO- (CH ₂ ) _p -R ₁₃ (IV)
in the
R _{12 is} a hydrogen atom, a C _1-6 alkyl or C _3-7 cyclo alkyl group or a terminal group through a phenyl, hetero aryl, trifluoromethyl, hydroxy, C _1-3 alkoxy, amino carbonyl, C _1-4 -alkylamino-carbonyl-, di- (C _1-4 -alkyl) -amino-carbonyl-, C _1-3 -alkyl-carbonyl-, C _1-3 -alkyl-sulfonylamino-, N- ( C _1-3 -alkyl) -C _1-3 -alkyl-sulfonylamino-, C _1-3 -alkyl-aminosulfonyl- or di- (C _1-3 -alkyl) -aminosulfonyl-group-substituted C _1-3 - Alkyl group and
p represents one of the numbers 0, 1, 2 or 3 and
R _{13 has} the meanings of the abovementioned group R ₇ or, if p represents one of the numbers 1, 2 or 3, also denotes a hydrogen atom,
a group of the formula
-N (R ₁₄ ) - (CH ₂ ) _q - (CO) _r -R ₁₅ (V)
in the
R _{14 is} a hydrogen atom, a C _1-4 alkyl group, a C _1-3 alkylcarbonyl, arylcarbonyl, phenylC _1-3 alkylcarbonyl, heteroarylcarbonyl, heteroarylC _1-3 alkylcarbonyl, C _1-4 -alkylsulfonyl-, arylsulfonyl-, phenyl-C _1-3 -alkylsulfonyl-, heteroarylsulfonyl- or heteroaryl-C _1-3 -alkyl-sulfonyl groups,
q one of the numbers 1, 2, 3 or 4,
r represents the number 1 or, if q is one of the numbers 2, 3 or 4, also the number 0 and
R _{15 has} the meanings of the above-mentioned group R ₇ ,
a group of the formula
-N (R ₁₆ ) -SO ₂ -R ₁₇ (VI),
in the
R _{16 is} a hydrogen atom or a C _1-4 alkyl group optionally substituted by a cyano, trifluoromethyl-carbonyl-amino or N- (C _1-3 -alkyl) -trifluoromethyl-carbonyl-amino group and
R _{17 represents} a C _1-3 alkyl group,
one by a di (C _1-3 alkyl) amino C _1-3 alkyl carbonyl or di (C _1-3 alkyl) amino C _1-3 alkyl sulfonyl group and a di - (C _1-3 alkyl) aminocarbonylC _1-3 alkyl group substituted amino group or
an N- (C _1-3 alkyl) -C _1-5 alkylsulfonylamino or N- (C _1-3 alkyl) phenylsulfonylamino group in which the alkyl part is additionally substituted by a cyano or carboxy group,
where all the single-bonded or fused-on phenyl groups contained in the radicals mentioned under R _{6 are represented} by fluorine, chlorine, bromine or iodine atoms, by C _1-5 -alkyl, trifluoromethyl, hydroxy, C _1-3 -alkoxy- , Carboxy-, C _1-3 -alkoxycarbonyl-, aminocarbonyl-, C _1-4 -alkylamino-car bonyl-, di- (C _1-4 -alkyl) -amino-carbonyl-, aminosulfonyl-, C _1-3 - Alkyl aminosulfonyl, di (C _1-3 alkyl) aminosulfonyl, C _1-3 alkyl sulfonylamino, nitro or cyano groups can be mono- or disubstituted, where the substituents can be the same or different, or two neighboring hydrogen atoms of the phenyl groups can be replaced by a methylene dioxy group,
and R _{5 represents} a hydrogen atom or a C _1-3 alkyl group,
where under the expression an aryl group, optionally by a fluorine, chlorine, bromine or iodine atom, by a cyano, trifluoromethyl, nitro, carboxylt aminocarbonyl, C _1-3 alkyl or C _1-3 alkoxy group mono- or disubstituted phenyl or naphthyl group and
under the expression a heteroaryl group, a monocyclic 5- or 6-membered heteroaryl group optionally substituted by a C _1-3 alkyl group in the carbon, where
the 6-membered heteroaryl group has one, two or three nitrogen atoms and
the 5-membered heteroaryl group is an imino group optionally substituted by a C _1-3 alkyl or phenylC _1-3 alkyl group, an oxygen or sulfur atom or
an imino group optionally substituted by a C _1-3 alkyl or phenyl-C _1-3 alkyl group or an oxygen or sulfur atom and additionally a nitrogen atom or
contains an imino group optionally substituted by a C _1-3 alkyl or phenylC _1-3 alkyl group and two nitrogen atoms,
and in addition, a phenyl ring can be fused to the abovementioned monocyclic heterocyclic groups via two adjacent carbon atoms and the bond takes place via a nitrogen atom or via a carbon atom of the heterocyclic part or an annexed phenyl ring,
to understand
the hydrogen atoms in the alkyl and alkoxy groups mentioned above or in the alkyl parts contained in the groups of formula I defined above can be partially or completely replaced by fluorine atoms,
and the hydrogen atom of an existing carboxy group or a hydrogen atom bonded to a nitrogen atom can in each case be replaced by a radical which can be split off in vivo,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts. 2. Indolinones of the general formula I according to claim 1, in which
R ₁ and R _{3 are} as defined above and
X is an oxygen atom,
R _{2 is} a carboxy group, a linear or branched C _1-6 alkoxy-carbonyl group, a C _5-7 cycloalkoxycarbonyl or a phenoxycarbonyl group,
a linear or branched C _1-3 alkoxycarbonyl group which is terminated in the alkyl part by a phenyl, heteroaryl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di ( C _1-3 alkyl) aminocarbonyl group is substituted,
a linear or branched C _2-3 alkoxy-carbonyl group which is terminated in the alkyl part by a chlorine atom, by a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _{1 -3} -alkyl) -amino group is substituted,
an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group which is optionally substituted in the 2-position of the ethyl group by a hydroxy or C _1-3 alkoxy group or, if R _{4 is} not aminosulfonylphenyl or N- (C _1-5 alkyl) - C Represents _1-3 alkylaminocarbonylphenyl group, also a di (C _1-2 alkyl) aminocarbonyl group,
R _{4 is} a C _3-7 cycloalkyl group,
wherein the methylene group in position 4 of a 6- or 7-membered cycloalkyl group is substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or by an -NH- or -N (C _1-3 alkyl) group can be replaced,
or a phenyl group substituted by the group R ₆ , which is additionally substituted by fluorine, chlorine or bromine atoms, by C _1-3 alkyl, trifluoromethyl, hydroxy, C _1-3 alkoxy, carboxy, C _{1 -3-} alkoxycarbonyl, amino, acetylamino, aminocarbonyl, C _1-3 alkyl aminocarbonyl, di (C _1-3 alkyl) aminocarbonyl, nitro or cyano groups can be mono- or disubstituted, where the substituents can be the same or different and where
R _{6 is} a hydrogen, fluorine, chlorine, bromine or iodine atom,
a cyano, nitro, amino, C _1-5 alkyl, C _3-7 cycloalkyl, trifluoromethyl, phenyl, tetrazolyl or heteroaryl group,
the group of the formula
in which a hydrogen atom bonded to a nitrogen atom can be replaced by a C _1-3 alkyl group,
a C _1-3 alkoxy group, an amino C _2-3 alkoxy, C _1-3 alkylamino C _1-3 alkoxy, di (C _1-3 alkyl) amino C _{2- 3} -alkoxy-, phenyl- C _1-3 -alkylamino-C _2-3 -alkoxy-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkyl amino-C _2-3 -alkoxy- , Pyrrolidino-C _2-3 alkoxy, Piperidino-C _2-3 alkoxy or C _1-3 alkyl mercapto group,
a carboxy, C _1-4 alkoxycarbonyl, aminocarbonyl, C _1-3 alkyl amino carbonyl, phenyl C _1-3 alkylamino carbonyl or N- (C _1-3 alkyl) phenyl -C _1-3 alkylaminocarbonyl group,
a C _3-7 cycloalkyl carbonyl group,
where the methylene group in position 4 of the 6 or 7-membered cycloalkyl part can be replaced by a -NH or -N (C _1-3 alkyl) group,
a 4- to 7-membered cycloalkyleneimino group in which
a methylene group linked to the imino group can be replaced by a carbonyl or sulfonyl group or
one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group or / and
each the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group by a carboxy-, C _1-3 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocar bonyl-, di- (C _1-3 -alkyl) - aminocarbonyl, phenyl-C _1-3 alkyl amino or N- (C _1-3 alkyl) phenyl-C _1-3 alkylamino group or
can be replaced by an oxygen or sulfur atom, by a sul finyl, sulfonyl, -NH or -N (C _1-3 alkyl) group,
a C _1-4 alkyl group terminally substituted by the group R ₇ , where
R _{7 is} a C _5-7 cycloalkyl group,
wherein the methylene group in position 4 of a 6- or 7- membered cycloalkyl group can be replaced by a -NH or -N (C _1-3 alkyl) group or
in a 5- to 7-membered cycloalkyl group a - (CH ₂ ) ₂ group can be replaced by a -CO-NH group, a - (CH ₂ ) ₃ group can be replaced by a -NH-CO-NH- can or a - (CH ₂ ) ₄ group can be replaced by an -NH-CO-NH-CO group, where in each case a hydrogen atom bonded to a nitrogen atom can be replaced by a C _1-3 alkyl group,
a phenyl or heteroaryl group,
a hydroxy or C _1-3 alkoxy group,
an amino, C _1-6 alkylamino, di (C _1-6 alkyl) amino, phenylamino, N-phenyl-C _1-3 -alkyl-amino-, phenyl-C _1-3 - alkyl- amino-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino- or di- (phenyl-C _1-3 -alkyl) -amino group,
a ω-hydroxy-C _2-3 -alkyl-amino-, N- (C _1-3 -alkyl) -ω-hy roxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _{2 -3-} alkyl) -amino-, di- (ω- (C _1-3 -alkoxy) -C _2-3 -alkyl) -amino- or N- (dioxolan-2-yl) -C _1-3 - alkyl amino group,
a C _1-3 -alkylcarbonylamino-C _2-3 -alkylamino- or C _1-3 -alkylcarbonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
a C _1-3 alkylsulfonylamino, N- (C _1-3 alkyl) -C _2-3 alkylsulfonylamino, C _1-3 alkylsulfonylaminoC _2-3 alkylamino or C _1-3 Alkylsulfonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
a hydroxycarbonyl-C _1-3 alkylamino or N- (C _1-3 alkyl) -hydroxycarbonyl-C _1-3 alkylamino group
a guanidino group in which a hydrogen atom can be replaced by a C _1-3 alkyl group,
a group of the formula
-N (R ₈ ) -CO- (CH ₂ ) _n -R ₉ (II),
in the
R _{8 is} a hydrogen atom or a C _1-3 alkyl group,
n one of the numbers 0, 1, 2 or 3 and
R _{9 is} an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, phenylamino, benzylamino or C _1-4 alkoxy group, a 5- to 7-membered cycloalkyleneimino group, where the methylene group in position 4 of the piperidino group is represented by an oxygen or sulfur atom, by a -NH-, -N (C _1-3 -alkyl) -, -N (phenyl) -, -N (C _1-3 -alkyl- carbonyl) - or -N (benzoyl) group can be replaced, or, if n represents one of the numbers 1, 2 or 3, also denote a hydrogen atom,
a group of the formula
-N (R ₁₀ ) - (CH ₂ ) _m - (CO) _o -R ₁₁ (III),
in the
R _{10 is} a hydrogen atom, a C _1-3 alkyl group, a C _1-3 alkylcarbonyl or C _1-3 alkylsulfonyl group,
m one of the numbers 1, 2 or 3,
o the number 1 or, if m is one of the numbers 2 or 3, also the number 0 and
R _{11 is} an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, C _1-4 alkoxy or C _1-3 alkoxyC _1-3 alkoxy group or a 5- to 7-membered cycloalkyleneimino group, the methylene group in position 4 of the piperidino group being represented by an oxygen or sulfur atom, by a -NH-, -N (C _1-3 -alkyl) -, -N (phenyl) -, - N (C _1-3 alkylcarbonyl) or -N (benzoyl) group can be replaced, mean
a C _4-7 cycloalkylamino or C _4-7 cycloalkenylamino group in which the position 1 of the ring is not involved in the double bond,
a 4- to 7-membered cycloalkyleneimino group in which
the cycloalkylene part can be condensed with a phenyl group or
one or two hydrogen atoms can each be replaced by a C _1-3 alkyl group or / and
the methylene group in position 3 of the pyrrolidino group can be substituted by a hydroxy or C _1-3 alkoxy group,
each the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group by a hydroxy, hydroxy-C _1-3 alkyl, C _1-3 alkoxy, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl -, C _1-3 alkyl aminocarbonyl, di (C _1-3 alkyl) aminocarbonyl, phenyl-C _1-3 alkylamino or N- (C _1-3 alkyl) phenyl-C _1-3 alkyl amino group substituted or
by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl) -, -N (phenyl) -, -N (phenyl-C _1-3 -alkyl- ) -, -N (C _1-3 -Alkyl-carbonyl) -, -N (C _1-4 -alkoxy-carbonyl -) -, -N (benzoyl) - or -N (phenyl-C _1-3 - alkyl-carbonyl) group can be replaced,
where a methylene group linked to an imino nitrogen atom of the cycloalkyleneimino group can be replaced by a carbonyl or sulfonyl group or in a 5- to 6-membered monocyclic or fused to a phenyl group cycloalkyleneimino group both methylene groups linked to the imino nitrogen atom by one each Carbonyl group can be replaced
means
or R _{6 is} a C _1-4 alkyl group which is terminated by a carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylaminocar bonyl or di (C _1-3 alkyl) - aminocarbonyl group or is substituted by a 4- to 7-membered cycloalkyleneiminocarbonyl group,
a group of the formula
-N (R ₁₂ ) -CO- (CH ₂ ) _p -R ₁₃ (IV)
in the
R _{12 is} a hydrogen atom, a C _1-3 alkyl, C _5-7 cycloalkyl, phenyl C _1-3 alkyl or heteroaryl C _1-3 alkyl group and
p represents one of the numbers 0, 1, 2 or 3 and
R _{13 has} the meanings of the abovementioned group R ₇ or, if p represents one of the numbers 1, 2 or 3, also denotes a hydrogen atom,
a group of the formula
-N (R ₁₄ ) - (CH ₂ ) _q - (CO) _r -R ₁₅ (V),
in the
R _{14 is} a hydrogen atom, a C _1-4 alkyl group, a C _1-3 alkyl carbonyl, phenyl carbonyl, phenyl C _1-3 alkyl carbonyl, heteroaryl carbonyl, heteroaryl C _1-3 alkyl carbonyl, C _1-4 alkylsulfonyl, phenylsulfonyl, phenyl-C _1-3 alkyl sulfonyl, heteroarylsulfonyl or heteroaryl C _1-3 alkyl sulfonyl groups,
q one of the numbers 1, 2, 3 or 4,
r represents the number 1 or, if q is one of the numbers 2, 3 or 4, also the number 0 and
R _{15 has} the meanings of the above-mentioned group _R 7,
a group of the formula
-N (R ₁₆ ) -SO ₂ -R ₁₇ (VI),
in the
R _{16 is} a hydrogen atom or a C _1-4 alkyl group optionally substituted by a cyano, trifluoromethyl-carbonyl-amino or N- (C _1-3 -alkyl) -trifluoromethyl-carbonyl-amino group and
R _{17 represents} a C _1-3 alkyl group,
one by a di (C _1-3 alkyl) amino C _1-3 alkyl carbonyl or di (C _1-3 alkyl) amino C _1-3 alkyl sulfonyl group and a di - (C _1-3 alkyl) aminocarbonylC _1-3 alkyl group substituted amino group,
where all the single-bonded or fused-on phenyl groups contained in the radicals mentioned under R ₆ by fluorine, chlorine or bromine atoms, by C _1-3 alkyl, trifluoromethyl, hydroxy, C _1-3 alkoxy, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino carbonyl, aminosulfonyl, C _1-3 alkylaminosulfonyl, nitro or cyano groups can be mono- or disubstituted, the substituents being the same or different can, or two adjacent hydrogen atoms of the phenyl groups can be replaced by a methylenedioxy group, and
R _{5 represents} a hydrogen atom or a C _1-3 alkyl group,
where, under a heteroaryl group mentioned above, a pyridinyl, pyrazinyl, pyrimidinyl, pyridazyl, pyrrolyl, furyl, thienyl, oxazolyl, thiazolyl, pyrazolyl, optionally substituted in the carbon skeleton by a C _1-3 alkyl group, Imidazolyl or triazolyl group, in which a hydrogen atom bonded to a nitrogen atom can be replaced by a C _1-3 alkyl or phenyl C _1-3 alkyl group and wherein the 5-membered, at least one imino group contain the heteroaryl groups via a carbon - or nitrogen atom are bound to understand
a hydrogen atom bound to a nitrogen atom in the abovementioned radicals can be replaced by a radical which can be split off in vivo,
the carboxy groups contained in the abovementioned radicals can each be substituted by a radical which can be split off in vivo,
the hydrogen atoms in the alkyl and alkoxy groups mentioned above or in the alkyl parts contained in the groups of formula I defined above can be replaced in whole or in part by fluorine atoms and
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts. 3. Indolinones of the general formula I according to claim 1, in which
X is an oxygen atom,
R _{1 is} a hydrogen atom,
R _{2 is} a carboxy group, a linear or branched C _1-4 alkoxycarbonyl group or a phenoxycarbonyl group,
a linear or branched C _1-3 alkoxy-carbonyl group which is terminated in the alkyl part by a phenyl, carboxy, C _1-3 alkoxy carbonyl, aminocarbonyl, C _1-3 alkylaminocarbonyl or di (C _{1 -3-} alkyl) -aminocarbonyl group is substituted,
a linear or branched C _2-3 alkoxy-carbonyl group which is terminated in the alkyl part by a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _1-3 alkyl ) amino group is substituted,
an aminocarbonyl or methylaminocarbonyl group, an ethylaminocarbonyl group which is optionally substituted in the 2-position of the ethyl group by a hydroxy or C _1-3 alkoxy group or, if R _{4 is} not aminosulfonylphenyl or N- (C _1-5 alkyl) - C Represents _1-3 alkylaminocarbonylphenyl group, also a di (C _1-2 alkyl) aminocarbonyl group,
R _{3 is} a C _1-4 alkyl group or a phenyl group which can be substituted by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C _1-3 alkyl, hydroxy or C _1-3 alkoxy group,
R _{4 is} a C _5-6 cycloalkyl group,
wherein the methylene group in position 4 of the cyclohexyl group is substituted by an amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group or by an -NH- or -N (C _1-3 Alkyl) group can be replaced,
a phenyl group, a phenyl group disubstituted by C _1-3 alkyl, C _1-3 alkoxy or nitro groups, where the substituents can be identical or different, or
a phenyl group substituted by the group R ₆ , which may additionally be substituted by a fluorine, chlorine or bromine atom or by an amino or nitro group, where R _{6 is} a fluorine, chlorine or bromine atom,
a C _1-3 alkyl, C _1-3 alkoxy, nitro, amino or C _5-6 cycloalkyl group,
a pyrrolyl, pyrazolyl, imidazolyl, triazolyl or tetrazolyl group bonded via a carbon atom, it being possible for the heteroaromatic groups mentioned in the carbon skeleton to be substituted by a C _1-3 alkyl group or a hydrogen atom bonded to a nitrogen atom by a C _{1- 3} -Alkyl- or phenyl-C _1-3 alkyl group can be replaced,
the group of the formula
a carboxy, C _1-4 alkoxycarbonyl, phenylC _1-3 alkyl amino carbonyl or C _5-7 cycloalkyl carbonyl group,
a 5- or 6-membered cycloalkyleneimino group, where
the methylene group in position 4 of the piperidino group can be replaced by an oxygen or sulfur atom, by an -NH or -N (C _1-3 alkyl) group,
an unbranched C _1-3 alkyl group which is terminally substituted by the group R ₇ , where
R _{7 is} a C _5-7 cycloalkyl group,
in a 5- or 6-membered cycloalkyl group a - (CH ₂ ) ₂ group can be replaced by a -CO-NH group, a - (CH ₂ ) ₃ group can be replaced by a -NH-CO-NH- may be or a - (CH ₂ ) ₄ group may be replaced by a -NH-CO-NH-CO group, where in each case a hydrogen atom bonded to a nitrogen atom may be replaced by a C _1-3 alkyl group,
a phenyl or pyridinyl group or a pyrrolyl, pyrazolyl, imidazolyl or triazolyl group bonded via a carbon or nitrogen atom, it being possible for the heteroaromatic groups mentioned in the carbon skeleton to be substituted by a C _1-3 alkyl group or a hydrogen atom bonded to a nitrogen atom can be replaced by a C _1-3 alkyl group,
a hydroxy or C _1-3 alkoxy group,
an amino, C _1-6 alkylamino, di (C _1-6 alkyl) amino, phenylamino, N-phenyl-C _1-3 -alkyl-amino-, phenyl-C _1-3 - al kylamino or N- (C _1-3 alkyl) phenyl-C _1-3 alkylamino group,
a ω-hydroxy-C _2-3 -alkyl-amino-, N- (C _1-3 -alkyl) -ω-hy droxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _{2 -3-} alkyl) -amino or di- (ω- (C _1-3 -alkoxy) -C _2-3 -alkyl) -amino group,
a C _1-3 -alkylcarbonylamino-C _2-3 -alkylamino- or C _1-3 -alkylcarbonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
a C _1-3 -alkylsulfonylamino-, N- (C _1-3 -alkyl) -C _1-3 -alkylsulfonylamino-, C _1-3 -alkylsulfonylamino-C _2-3 -alkylamino- or
C _1-3 alkylsulfonylamino-C _2-3 alkyl-N- (C _1-3 alkyl) amino group,
a hydroxycarbonyl-C _1-3 -alkylamino- or N- (C _1-3 -alkyl) -hydroxycarbonyl-C _1-3 -alkyl-amino group,
a guanidino group in which a hydrogen atom can be replaced by a C _1-3 alkyl group,
a group of the formula
-N (R ₈ ) -CO- (CH ₂ ) _n -R ₉ (II),
in the
R _{8 is} a hydrogen atom or a C _1-3 alkyl group,
n one of the numbers 0, 1, 2 or 3 and
R _{9 is} an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino or C _1-4 alkoxy group, a 5- or 6-membered cycloalkyleneimino group, with the methylene group in position 4 the piperidino group can be replaced by an -NH-, -N (C _1-3 -alkyl) - or -N (C _1-3 -alkyl-carbonyl) group, or, if n is one of the numbers 1, 2 or 3 also represents a hydrogen atom,
a group of the formula
-N (R ₁₀ ) - (CH ₂ ) _m - (CO) _o -R ₁₁ (III),
in the
R _{10 represents} a hydrogen atom or a C _1-3 alkyl group,
m one of the numbers 1, 2 or 3,
o the number 1 or, if m is one of the numbers 2 or 3, also the number 0 and
R _{11 is} an amino, C _1-3 alkylamino, di (C _1-3 alkyl) amino, C _1-4 alkoxy or methoxyC _1-3 alkoxy group or a 5- or 6th -linked cycloalkyleneimino group, where the methyl group in position 4 of the piperidino group can be replaced by an -NH-, -N (C _1-3 -alkyl) - or -N (C _1-3 -alkyl-carbonyl) group ,
an azetidino, pyrrolidino, piperidino, 2,6-dimethyl-piperidino, 3,5-dimethyl-piperidino or azepino group, wherein
the methylene group in position 3 of the pyrrolidino group can be substituted by a hydroxyl group,
the methylene group in position 4 of the piperidino group is substituted by a hydroxy, hydroxyC _1-3 alkyl or C _1-3 alkoxy group or
through an oxygen or sulfur atom, through a sulfinyl, sulfonyl, -NH-, -N (C _1-3 alkyl) -, -N (C _1-3 alkyl carbonyl) -, -N (benzoyl ) - or -N (phenyl-C _1-3 alkyl carbonyl) group can be replaced,
a methylene group linked to an imino nitrogen atom of the pyrrolidino, piperidino or piperazino group can be replaced by a carbonyl group,
means
or R _{6 is} a straight-chain C _1-3 alkyl group which is terminally substituted by a carboxy or C _1-3 alkoxy carbonyl group,
a group of the formula
-N (R ₁₂ ) -CO- (CH ₂ ) _p -R ₁₃ (IV),
in the
R _{12 is} a hydrogen atom, a C _1-3 alkyl or phenylC _1-3 alkyl group,
p one of the numbers 0, 1 or 2 and
R _{13 is} an amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, benzylamino, N- (C _1-3 alkyl) benzylamino, C _1-3 alk oxy-C _1-3 -alkylamino-, N- (C _1-3 -alkyl) -C _1-3 -alkoxy-C _1-3 -alkylamino-, di- (2-methoxy-ethyl) -amino-, Di- (ω-hydroxy-C _2-3 -alkyl) -amino or aminocarbonyl-methyl-N- (methyl) -amino group,
a pyrrolyl, pyrazolyl or imidazolyl group bonded via a nitrogen atom and optionally substituted by a C _1-3 alkyl group,
a pyrrolidino, piperidino, morpholino, thio morpholino or a in the 4-position, optionally by a C _1-3 alkyl, phenyl C _1-3 alkyl, C _1-3 alkyl carbonyl or C _1-4 alkoxy-carbonyl group-substituted piperazino group or, if n represents the number 1 or 2, also denote a hydrogen atom,
a group of the formula
-N (R ₁₄ ) - (CH ₂ ) _q - (CO) _r -R ₁₅ (V)
in the
R _{14 is} a hydrogen atom, a C _1-4 alkyl, C _1-3 alkyl carbonyl, phenylcarbonyl, phenyl C _1-3 alkylcarbonyl, furyl carbonyl, pyridinyl carbonyl, furyl C _{1- 3-} alkylcarbonyl, pyridinyl-C _1-3 -alkylcarbonyl, C _1-4 -alkylsulfonyl, phenylsulfonyl or phenyl-C _1-3 -alkylsulfonyl group,
q one of the numbers 1, 2 or 3,
r represents the number 1 or, if q is one of the numbers 2 or 3, also the number 0 and
R _{15 is} an amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino or N- (C _1-4 alkyl) benzylamino group,
or a group of the formula
-N (R ₁₆ ) -SO ₂ -R ₁₇ (VI),
in the
R ₁₆ is a hydrogen atom or a terminally substituted by a cyano, trifluoromethyl-carbonyl-amino or N- (C _1-3 alkyl) -trifluoromethyl-carbonyl-amino group of sub-substituted C _1-3 alkyl group and
R _{17 represents} a C _1-3 alkyl group,
where all of the monobonded or fused phenyl groups contained in the radicals mentioned under R ₆ can be substituted by a fluorine, chlorine or bromine atom, by a methyl, trifluoromethyl, methoxy, nitro or cyano group and
R _{5 represents} a hydrogen atom,
where a hydrogen atom bonded to a nitrogen atom in the abovementioned radicals can be replaced by an acetyl or tert-butoxycarbonyl group and
the carboxy groups contained in the abovementioned radicals can also be in the form of the tert-butoxycarbonyl precursor group,
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts. 4. Indolinones of the general formula I according to claim 1, in which
X is an oxygen atom,
R ₁ and R ₅ each represent a hydrogen atom,
R _{2 is} a methoxycarbonyl, ethoxycarbonyl or aminocarbonyl group,
R _{3 is} a phenyl group and
R _{4 is} a phenyl group monosubstituted by the group R ₆ , where at
R _{6 is} an N-methylimidazol-2-yl group,
an unbranched C _1-3 alkyl group which is terminally substituted by a C _1-4 alkylamino, di (C _1-4 alkyl) amino, piperidino or 2,6-dimethylpiperidino group,
a group of the formula
-N (R ₁₂ ) -CO- (CH ₂ ) _p -R ₁₃ (IV),
in the
R _{12 is} a C _1-3 alkyl group,
p one of the numbers 1 or 2 and
R _{13 is} a di (C _1-3 alkyl) amino group,
or a group of the formula
-N (R ₁₄ ) - (CH ₂ ) _q - (CO) _r -R ₁₅ (V)
in the
R _{14 is} a C _1-3 alkylcarbonyl or C _1-3 alkylsulfonyl group,
q one of the numbers 1, 2 or 3,
r the number 1 or, if q is one of the numbers 2 or 3, the number 0 and
R _{15 represents} a di (C _1-3 alkyl) amino group,
represent
their tautomers, their diastereomers, their enantiomers, their mixtures and their salts. 5. The following substituted indolinones of the general formula I according to claim 1:

• a) 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• b) 3-Z - [(1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-carbamoyl-2-indolinone,
• c) 3-Z- [1- (4- (piperidin-1-ylmethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,
• d) 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• e) 3-Z- [1- (4 - ((2,6-dimethylpiperidin-1-yl) methyl) anilino) - 1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• f) 3-Z- [1- (4- (N- (2-dimethylamino-ethyl) -N-acetylamino) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• g) 3-Z- [1- (4- (N- (3-Dimethylamino-propyl) -N-acetylamino) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• h) 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonylamino) -anilino) -1-phenylmethylene] -6-ethoxycarbonyl-2-indolinone,
• i) 3-Z- [1- (4- (dimethylaminomethyl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,
• j) 3-Z- [1- (4- (N-acetyl-N-dimethylaminocarbonylmethylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,
• k) 3-Z- [1- (4-ethylaminomethyl-anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,
• l) 3-Z- [1- (4- (1-methylimidazol-2-yl) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,
• m) 3-Z- [I- (4- (N-dimethylaminomethylcarbonyl-N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,
• n) 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-methylsulfonyl-amino) -anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,
• o) 3-Z- [1- (4- (N- (3-dimethylamino-propyl) -N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolino non,
• p) 3-Z- [1- (4- (N-dimethylaminocarbonylmethyl-N-methylsulfonylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indoli non,
• q) 3-Z- [1- (4- (N - ((2-Dimethylaminoethyl) carbonyl) -N-methylamino) anilino) -1-phenylmethylene] -6-methoxycarbonyl-2- indo linon,
• r) 3-Z- [1- (4- (N- (2-Dimethylamino-ethyl) -N-acetylamino) -anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone and
• s) 3-Z- [1- (4-methylaminomethyl-anilino) -1-phenylmethylene] -6-methoxycarbonyl-2-indolinone,

their tautomers, their mixtures and their salts. 6. Physiologically acceptable salts of the compounds according to the Claims 1 to 5. 7. Medicament containing a compound according to at least one of claims 1 to 5 or a salt according to claim 6 ne ben optionally one or more inert carriers and / or diluents. 8. Use of a connection according to at least one of the An claims 1 to 5 or a salt according to claim 6 for the preparation a medicine used to treat excessive or abnormal cell proliferation is suitable. 9. Process for the manufacture of a medicament according to An Proverb 7, characterized in that in a non-chemical way a connection according to at least one of claims 1 to 5  or a salt according to claim 6 in one or more inert Carriers and / or diluents are incorporated. 10. A process for the preparation of the compounds according to claims 1 to 6, characterized in that

• a) a compound of the general formula
  in the
  X and R _{3 are defined} as mentioned in claims 1 to 5, R ₂ 'has the meanings mentioned for R ₂ in claims 1 to 5,
  R _{18 is} a hydrogen atom or a protective group for the nitrogen atom of the lactam group, where one of the radicals R ₂ 'and R _{18 can} also be an optionally formed via a spacer binding to a solid phase and the other of the radicals R ₂ ' and R ₇ has the meanings mentioned above, and Z _{1 represents} a halogen atom, a hydroxyl, alkoxy or aryl alkoxy group,
  with an amine of the general formula
  in the
  R ₄ and R _{5 are} as defined in claims 1 to 5, implemented and, if necessary, a protective group used for the nitrogen atom of the lactam group or a compound thus obtained is cleaved from a solid phase, or
• b) for the preparation of a compound of general formula I in which
  R _2, with the exception of the carboxy group as defined in claims 1 to 5, is a compound of the general formula
  in the
  R ₁ and R ₃ to R _{5 are defined} as mentioned in claims 1 to 5, or their reactive derivatives with a compound of the general formula
  HR ₁₉ (X),
  in the
  R _{19 is} a C _1-6 alkanol, a C _4-7 cycloalkanol or an aromatic alcohol,
  a C _1-6 alkanol, which is terminated in the alkyl part by a phenyl, heteroaryl, carboxy, C _1-3 alkoxycarbonyl, aminocarbonyl, C _1-3 alkylamino carbonyl or di (C _1-3 alkyl) aminocarbonyl group is substituted,
  a C _2-6 alkanol which is terminal in the alkyl part by a chlorine atom or a hydroxy, C _1-3 alkoxy, amino, C _1-3 alkylamino or di (C _1-3 alkyl) amino group is substituted,
  represents an amino or methylamino group, an ethylamino group which is optionally substituted by a hydroxy or C _1-3 -alkoxy group in the 2-position of the ethyl group or a di- (C _1-2 -alkyl) amino group, is reacted or
• c) for the preparation of a compound of general formula I in which R _{4 is} one through the group
  R _{7 represents} substituted C _1-4 alkyl group, wherein
  R _{7 is} an amino, C _1-7 alkylamino, di (C _1-7 alkyl) amino, phenylamino, N-phenyl-C _1-3 alkylamino, phenyl-C _{1- 3} -al kylamino-, N- (C _1-3 -alkyl) -phenyl-C _1-3 -alkylamino- or di- (phenyl-C _1-3 -alkyl) -amino group,
  a ω-hydroxy-C _2-3 -alkyl-amino-, N- (C _1-3 -alkyl) -ω-hy droxy-C _2-3 -alkyl-amino-, di- (ω-hydroxy-C _{2 -3-} alkyl) -amino-, di- (ω- (C _1-3 -alkoxy) -C _2-3 -alkyl) -amino- or N- (dioxolan-2-yl) -C _1-3 - alkyl amino group,
  a C _1-3 -alkylcarbonylamino-C _2-3 -alkylamino- or C _1-3 -alkylcarbonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
  a C _1-3 alkylsulfonylamino, N- (C _1-3 alkyl) -C _1-3 alkylsulfonylamino, C _1-3 alkylsulfonylaminoC _2-3 alkylamino or C _1-3 Alkylsulfonylamino-C _2-3 -alkyl-N- (C _1-3 -alkyl) -amino group,
  a group of the formula
  -N (R ₁₀ ) - (CH ₂ ) _m - (CO) _o -R ₁₁ (III),
  in the
  R _{10 is} a hydrogen atom, a C _1-3 alkyl group, a C _1-3 alkylcarbonyl, arylcarbonyl, phenyl C _1-3 alkylcarbonyl, C _1-3 alkylsulfonyl, arylsulfonyl or phenyl-C _1-3 alkylsulfonyl group,
  m one of the numbers 1, 2, 3 or 4,
  o the number 1 and
  R _{11 is} an amino, C _1-4 alkylamino, di (C _1-4 alkyl) amino, phenylamino, N- (C _1-4 alkyl) phenylamino, benzylamino, N- (C _1-4 alkyl) benzylamino, C _1-4 alkoxy or C _1-3 alkoxy-C _1-3 alkoxy group, one in the 1-position optionally substituted by a C _1-3 alkyl group Di (C _1-4 alkyl) aminoC _1-3 alkylamino group or a 4- to 7- membered cycloalkyleneimino group, where the cycloalkylene part can be condensed with a phenyl ring or the methylene group in position 4 of a 6- or 7-membered cycloalkyleneimino group through an oxygen or sulfur atom, through a sulfinyl, sulfonyl, -NH-, -N (C _1-3 -alkyl) -, -N (phenyl) -, -N (C _{1 -3-} alkyl-carbonyl) - or -N (benzoyl) group may be replaced, mean
  a C _4-7 cycloalkylamino, C _4-7 cycloalkyl-C _1-3 alkylamino or C _4-7 cycloalkenylamino group in which position 1 of the ring is not involved in the double bond and wherein the groups mentioned above can each additionally be substituted on the amine nitrogen atom by a C _5-7 -cycloalkyl, C _2-4 -alkenyl or C _1-4 -alkyl group,
  or a 4- to 7-membered cycloalkyleneimino group in which
  the cycloalkylene part with a phenyl group or with an oxazolo, imida optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a nitro, C _1-3 alkyl, C _1-3 alkoxy or amino group zolo, thiazolo, pyridino, pyrazino or pyrimidino group can be condensed or / and
  one or two hydrogen atoms can each be replaced by a C _1-3 alkyl, C _5-7 cycloalkyl or phenyl group or / and
  the methylene group in position 3 of a 5-membered cycloalkyleneimino group may be substituted by a hydroxy, hydroxy c _1-3 alkyl, C _1-3 alkoxy or C _1-3 alkoxy-C _1-3 alkyl group can,
  each the methylene group in position 3 or 4 of a 6- or 7-membered cycloalkyleneimino group by a hydroxy, hydroxy-C _1-3 -alkyl-, C _1-3 -alkoxy-, C _1-3 -alkoxy-C _{1- 3-} alkyl-, C _1-4 -alkoxycarbonyl-, aminocarbonyl-, C _1-3 -alkylaminocarbonyl-, di- (C _1-3 -alkyl) -aminocarbonyl-, phenyl-C _1-3 -alkylamino- or N- (C _1-3 alkyl) phenyl-C _1-3 alkylamino group substituted or
  by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, -NH-, -N (C _1-3 alkyl -) -, -N (phenyl) -, -N (phenyl-C _1-3 alkyl) -) -, -N (C _2-3 -Alkyl-carbonyl -) -, -N ( _1-4 -alkoxy-carbonyl -) -, -N (Ben zoyl -) - or -N (phenyl-C _{1 -3-} alkyl-carbonyl -) - group can be replaced,
  where a methylene group linked to an imino nitrogen atom of the cycloalkyleneimino group can be replaced by a carbonyl or sulfonyl group or in a 5- to 7-membered monocyclic or fused to a phenyl group cycloalkylene lenimino group, both methylene groups linked to the imino nitrogen atom, each by a car bonyl group can be replaced
  means
  a compound of the general formula
  in the
  R ₃ , R ₅ and X are as defined in claims 1 to 5,
  R ₂ 'has the meanings mentioned for R ₂ in claims 1 to 5,
  R _{18 is} a hydrogen atom or a protective group for the nitrogen atom of the lactam group, where one of the radicals R ₂ 'and R _{18 can} also represent a bond, optionally formed via a spacer, to a solid phase and the other of the radicals R ₂ ' and R ₁₈ is has the meanings mentioned above, A represents a C _1-4 alkyl group and Z _{2 represents} a leaving group, with an amine of the general formula
  HR ₇ (XII),
  in the
  R ₇ , which has the meanings given above for R ₇ , is converted and, if necessary, a protective group used for the nitrogen atom of the lactam group or a compound thus obtained is split off from a solid phase and
  if desired, a compound of the general formula I thus obtained which contains an alkoxycarbonyl group is subsequently converted into a corresponding carboxy compound by hydrolysis or
  a compound of the general formula 1 thus obtained, which contains an amino or alkylamino group, is converted into a corresponding alkylamino or dialkyl amino compound by means of reductive alkylation or
  a compound of the general formula I thus obtained, which contains an amino or alkylamino group, is converted into a corresponding acyl or sulfonyl compound by means of acylation or sulfonation, or
  a compound of the general formula I thus obtained, which contains a carboxy group, is converted into an appropriate ester or aminocarbonyl compound by esterification or amidation or
  a compound of the general formula I thus obtained, which contains a cycloalkyleneimino group in which a methylene group is replaced by a sulfur atom, is converted into a corresponding sulfinyl or sulfonyl compound by oxidation, or
  a compound of the general formula I thus obtained, which contains a nitro group, is converted into an appropriate amino compound by reduction or
  a compound of the general formula I thus obtained, in which R _{4 represents} a phenyl group substituted by an amino, alkylamino, aminoalkyl or N-alkylamino group, by reaction with a corresponding cyanate, isocyanate or carbamoyl halide in a corresponding urea compound general formula I is transferred or
  a compound of the general formula I thus obtained, in which R _{4 represents} a phenyl group substituted by an amino, alkylamino, aminoalkyl or N-alkylamino group, by reaction with a corresponding compound transferring the amidino group or by reaction with a corresponding one Nitrile is converted into a corresponding guanidino compound of the general formula I or
  if necessary, a protective residue used during the reactions to protect reactive groups is split off or
  if desired, a compound of the general formula I thus obtained is subsequently separated into its stereoisomers or
  a compound of the general formula I obtained in this way is converted into its salts, in particular for pharmaceutical use into its physiologically tolerable salts with an inorganic or organic acid or base.