Claims
- 1. A compound of the formula I
- 2. A compound of formula I according to claim 1 wherein the sulphonylamino group of the formula R2—SO2NR6— is linked to the 5-position of the indolinone group.
- 3. A compound of formula I according to claim 1, wherein:
R3 is a phenyl group optionally substituted by a fluorine, chlorine or bromine atom, by a C1-3-alkyl, hydroxy, C1-3-alkoxy, C1-3-alkylsulphenyl, C1-3-alkylsulphinyl, C1-3-alkylsulphonyl, phenylsulphenyl, phenylsulphinyl, phenylsulphonyl, nitro, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, C2-5-alkanoylamino or N-(C1-3-alkylamino)-C2-5-alkanoylamino group.
- 4. A compound of formula I according to claim 1, wherein:
R2 is a C1-3-alkyl group optionally substituted by one or more halogen atoms or a phenyl group or a C2-4-alkenyl group optionally substituted by a phenyl group, wherein the phenyl moiety in each case may be substituted by a fluorine, chlorine, bromine or iodine atom or by a C1-3-alkyl or C1-3-alkoxy group.
- 5. A compound of formula I according to claim 1, wherein:
X is an oxygen atom, R1 is a hydrogen atom, R2 is a C1-3-alkyl group optionally substituted by one or more fluorine atoms or a phenyl group or a C2-4-alkenyl group optionally substituted by a phenyl group; a phenyl group which may be mono- or disubstituted by fluorine, chlorine, bromine or iodine atoms, by C1-3-alkyl or C1-3-alkoxy groups, wherein the substituents may be identical or different,
a phenyl group substituted by a trifluoromethyl, carboxy, C1-3-alkoxycarbonyl, aminocarbonyl, cyano, aminomethyl, nitro or amino group, a C4-6-alkyl, C3-7-cycloalkyl, trimethylphenyl or naphthyl group, or a pyridinyl, quinolyl, isoquinolyl, oxazolyl, isoxazolyl, imidazolyl or 1-(C1-3-alkyl)-imidazolyl group optionally substituted by a C1-3-alkyl group, R3 is a hydrogen atom or a C1-4-alkyl group, or
a phenyl group optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a C1-3-alkyl, C1-3-alkoxy, nitro or amino group, R4 is a phenyl group optionally substituted by R7, R5 and R6 in each case denote a hydrogen atom, and R7 is a fluorine, chlorine, bromine or iodine atom,
a methoxy, nitro, cyano, carboxy, C1-3-alkoxycarbonyl, aminocarbonyl, C1-3-alkylaminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, phenyl-C1-3-alkylaminocarbonyl, N-(phenyl-C1-3-alkyl)-C1-3-alkylaminocarbonyl or 5- to 7-membered cycloalkyleneiminocarbonyl group, a C1-3-alkyl group which is substituted by a carboxy, C1-3-alkoxycarbonyl, aminocarbonyl, C1-3-alkylaminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, phenyl-C1-3-alkylaminocarbonyl, N-(phenyl-C1-3-alkyl)-C1-3-alkylaminocarbonyl, 5- to 7-membered cycloalkyleneiminocarbonyl, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, phenyl-C1-3-alkylamino, N-(phenyl-C1-3-alkyl)-C1-3-alkylamino or 5- to 7-membered cycloalkyleneimino group, while the abovementioned 5- to 7-membered cycloalkyleneimino group may be substituted by one or two C1-3-alkyl groups, which may in turn be terminally substituted by a hydroxy, amino or C2-4-alkanoylamino group, and at the same time in the abovementioned 5- to 7-membered cycloalkyleneimino moieties a methylene group in the 2 position may be replaced by a carbonyl group or in the abovementioned 6- and 7-membered cycloalkyleneimino moieties a methylene group in the 4 position may be replaced by an oxygen atom, by an imino, N-(C1-3-alkyl)-imino, N-(phenyl-C1-3-alkyl)-imino or N-(C1-5-alkoxycarbonyl)-imino group, an amino, C1-3-alkylamino, phenyl-C1-3-alkylamino, C1-5-alkanoylamino, phenyl-C1-4-alkanoylamino, C1-5-alkoxycarbonylamino, phenyl-C1-3-alkoxycarbonylamino, C1-5-alkylsulphonylamino, phenyl-C1-3-alkylsulphonylamino- or phenylsulphonylamino group, wherein the hydrogen atom of the amino group may be replaced by a C1-3-alkyl group, while the C1-3-alkyl moiety may be substituted by a carboxy, C1-3-alkoxycarbonyl, aminocarbonyl, C1-3-alkylaminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, phenyl-C1-3-alkylaminocarbonyl, N-(phenyl-C1-3-alkyl)-C1-3-alkylaminocarbonyl, 2-dimethylaminoethylaminocarbonyl, N-methyl-(2-dimethylaminoethyl)-aminocarbonyl- or C4-6-cycoalkylenimnocarbonyl group or from position 2 by an amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, phenyl-C1-3-alkylamino, N-(phenyl-C1-3-alkyl)-C1-3-alkylamino, C2-5-alkanoylamino, N-(C1-3-alkyl)-C2-5-alkanoylamino, C1-5-alkoxycarbonylamino- or N-(C1-5-alkoxycarbonyl)-C1-3-alkylamino group.
- 6. A compound of formula I according to claim 1, wherein:
R2 is a C1-3-alkyl group optionally substituted by a phenyl group, a C1-3-perfluoroalkyl group or a phenylvinyl group,
a phenyl group which may be substituted by a fluorine, chlorine, bromine or iodine atom, by a C1-3-alkyl, C1-3-alkoxy, nitro, amino, cyano, cyanomethyl or aminomethyl group, a C4-6-alkyl, C3-7-cycloalkyl, trimethylphenyl or naphthyl group, a pyridinyl, quinolyl, isoquinolyl, oxazolyl, isoxazolyl, imidazolyl or 1-(C1-3-alkyl)-imidazolyl group optionally substituted by a C1-3-alkyl group, R3 is a phenyl group optionally substituted by a fluorine, chlorine, bromine or iodine atom, by a C1-3-alkyl, C1-3-alkoxy, nitro or amino group, R4 is a phenyl group which may be substituted by R7 and additionally by a chlorine atom or a nitro group, while R7 is a fluorine, chlorine, bromine or iodine atom,
a methoxy, nitro, cyano, carboxy, methoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, benzylaminocarbonyl, N-benzyl-methylaminocarbonyl, pyrrolidinocarbonyl or piperidinocarbonyl group, a methyl or ethyl group which may be substituted by a carboxy, methoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, benzylaminocarbonyl, N-benzyl-methylaminocarbonyl, pyrrolidinocarbonyl, piperidinocarbonyl, amino, methylamino, dimethylamino, benzylamino, N-benzylmethylamino, C2-4-alkanoylamino, N-methyl-C2-4-alkanoylamino, tert.butyloxycarbonylamino, N-methyl-tert.butyloxycarbonylamino, pyrrolidino, pyrrolidinomethyl, hydroxypyrrolidinomethyl, hydroxymethylpyrrolidinomethyl, piperidino, dimethylpiperidino, 2-oxo-piperidino, piperazino, 4-methyl-piperazino, 4-benzyl-piperazino, 4-tert.butoxycarbonyl-piperazino or morpholino group, or an amino, methylamino, ethylamino, C1-3-alkanoylamino, phenylacetylamino, tert.butoxycarbonylamino, C1-4-alkylsulphonylamino, phenyl-methylsulphonylamino or phenylsulphonylamino group, wherein the hydrogen atom of the amino group may be replaced by a methyl or ethyl group, while the methyl or ethyl moiety in each case may be substituted by a carboxy, methoxycarbonyl, aminocarbonyl, methylaminocarbonyl or dimethylaminocarbonyl group or the ethyl moiety may also be substituted from position 2 by an amino, methylamino, dimethylamino, benzylalkylamino, N-benzyl-methylamino, C2-3-alkanoylamino, N-methyl-C2-3-alkanoylamino, tert.butyloxycarbonylamino or N-methyl-tert.butyloxycarbonylamino group.
- 7. A compound of formula I according to claim 1, wherein R4 is a phenyl group substituted in the 4 position by R7.
- 8. A compound of the formula IA
- 9. A compound of formula IA according to claim 8 wherein R7 is selected from the group consisting of:
hydrogen, (2,6-dimethylpiperidino)-methyl, (N-ethylsulphonyl)-N-(2-dimethylaminoethyl)-aminocarbonylmethyl)-amino, N-ethylsulphonyl-N-(N-(2-dimethylaminoethyl)-N-methyl-amino-carbonylmethyl)-amino, 2-oxopiperidinomethyl, 4-benzyl-piperazino-methyl, 4-methylpiperazino-methyl, 4-tert.butoxycarbonyl-piperazinomethyl, acetylamino, acetylaminomethyl, amino, aminomethyl, benzylaminocarbonyl, benzylaminocarbonyl-methyl, carboxy, carboxymethyl, chlorine, cyano, dimethylaminocarbonyl-methylamino, dimethylaminoethyl, dimethylaminomethyl, ethoxycarbonylmethyl, ethylsulphonylamino, formylamino, methoxycarbonyl, methylsulphonylamino, morpholinomethyl, N-(2-(N-acetyl-N-methyl-amino)-ethyl)-ethylsulphonylamino, N-(2-(N-acetyl-N-methyl-amino)-ethyl)-methylsulphonylamino, N-(2-(N-acetyl-N-methyl-amino)-ethyl)-propionylamino, N-(2-(N-acetyl-N-methyl-amino)-ethylamino, N-(2-(N-benzyl-N-methyl-amino)-ethyl)-propionylamino, N-(2-acetylamino-ethyl)-N-acetyl-amino, N-(2-acetylamino-ethyl)-N-ethylsulphonyl-amino, N-(2-acetylamino-ethyl)-N-methylsulphonyl-amino, N-(2-acetylamino-ethyl)-N-propionyl-amino, N-(2-aminoethyl)-N-methylsulphonyl-amino, N-(2-dimethylamino-ethyl)-N-acetyl-amino, N-(2-dimethylamino-ethyl)-N-butylsulphonyl-amino, N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino, N-(2-dimethylamino-ethyl)-N-phenylsulphonyl-amino, N-(2-dimethylaminoethyl)-N-propylsulphonyl-amino, N-(2-methylamino-ethyl)-acetylamino, N-(2-methylamino-ethyl)-N-methylsulphonyl-amino, N-(2-methylamino-ethyl)-propionylamino, N-(2-propionylamino-ethyl)-N-propionyl-amino, N-(aminocarbonyl-methyl)-N-methylsulphonyl-amino, N-(dimethylamino-carbonylmethyl)-N-(methylsulphonyl-amino, N-(dimethylaminoethyl)-N-methylsulphonyl-amino, N-(methylaminocarbonyl-methyl)-N-methylsulphonyl-amino, N-(piperidinomethyl-carbonyl)-N-methyl-amino, N-acetyl-N-(2-(N-benzyl-N-methyl-amino)-ethylamino, N-acetyl-N-(2-benzyl-oxycarbonylamino-ethyl)-amino, N-carboxylmethyl-N-methylsulphonyl-amino, N-ethylsulphonyl-N-hydroxycarbonylmethyl-amino, N-methyl-N-acetyl-amino, N-methyl-N-ethyl sulphonyl-amino, N-methyl-N-formyl-amino, N-methyl-N-methylsulphonyl-amino, N-methyl-N-propionyl-amino, piperazinomethyl, propionylamino, pyrrolidin-1-yl-methyl, 2-hydroxymethylpyrrolidin-1-yl-methyl, 3-hydroxypyrrolidin-1-yl-methyl and tert.butoxycarbonylamino.
- 10. A compound of formula IB
- 11. A compound of formula IB according to claim 10 wherein:
R7 is selected from the group consisting of:
hydrogen, (2,6-dimethylpiperidino)-methyl, (N-ethylsulphonyl)-N-(2-dimethylaminoethyl)-aminocarbonylmethyl)-amino, N-ethylsulphonyl-N-(N-(2-dimethylaminoethyl)-N-methyl-amino-carbonylmethyl)-amino, 2-oxopiperidinomethyl, 4-benzyl-piperazino-methyl, 4-methylpiperazino-methyl, 4-tert.butoxycarbonyl-piperazinomethyl, acetylamino, acetylaminomethyl, amino, aminomethyl, benzylaminocarbonyl, benzylaminocarbonyl-methyl, carboxy, carboxymethyl, chlorine, cyano, dimethylaminocarbonyl-methylamino, dimethylaminoethyl, dimethylaminomethyl, ethoxycarbonylmethyl, ethylsulphonylamino, formylamino, methoxycarbonyl, methylsulphonylamino, morpholinomethyl, N-(2-(N-acetyl-N-methyl-amino)-ethyl)-ethylsulphonylamino, N-(2-(N-acetyl-N-methyl-amino)-ethyl)-methylsulphonylamino, N-(2-(N-acetyl-N-methyl-amino)-ethyl)-propionylamino, N-(2-(N-acetyl-N-methyl-amino)-ethylamino, N-(2-(N-benzyl-N-methyl-amino)-ethyl)-propionylamino, N-(2-acetylamino-ethyl)-N-acetyl-amino, N-(2-acetylamino-ethyl)-N-ethylsulphonyl-amino, N-(2-acetylamino-ethyl)-N-methylsulphonyl-amino, N-(2-acetylamino-ethyl)-N-propionyl-amino, N-(2-aminoethyl)-N-methylsulphonyl-amino, N-(2-dimethylamino-ethyl)-N-acetyl-amino, N-(2-dimethylamino-ethyl)-N-butylsulphonyl-amino, N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino, N-(2-dimethylamino-ethyl)-N-phenylsulphonyl-amino, N-(2-dimethylaminoethyl)-N-propylsulphonyl-amino, N-(2-methylamino-ethyl)-acetylamino, N-(2-methylamino-ethyl)-N-methylsulphonyl-amino, N-(2-methylamino-ethyl)-propionylamino, N-(2-propionylamino-ethyl)-N-propionyl-amino, N-(aminocarbonyl-methyl)-N-methylsulphonyl-amino, N-(dimethylamino-carbonylmethyl)-N-(methylsulphonyl-amino, N-(dimethylaminoethyl)-N-methylsulphonyl-amino, N-(methylaminocarbonyl-methyl)-N -methylsulphonyl-amino, N-(piperidinomethyl-carbonyl)-N-methyl-amino, N-acetyl-N-(2-(N-benzyl-N-methyl-amino)-ethylamino, N-acetyl-N-(2-benzyl-oxycarbonylamino-ethyl)-amino, N-carboxylmethyl-N-methylsulphonyl-amino, N-ethylsulphonyl-N-hydroxycarbonylmethyl-amino, N-methyl-N-acetyl-amino, N-methyl-N-ethylsulphonyl-amino, N-methyl-N-formyl-amino, N-methyl-N-methylsulphonyl-amino, N-methyl-N-propionyl-amino, piperazinomethyl, propionylamino, pyrrolidin-1-yl-methyl, 2-hydroxymethylpyrrolidin-1-yl-methyl, 3-hydroxypyrrolidin-1-yl-methyl and tert.butoxycarbonylamino; and R2 is selected from the group consisting of:
1-methyl-1H-imidazol-4-yl, 2-aminophenyl, 2-chlorophenyl, 2-cyanophenyl, 2-nitrophenyl, 2-phenylethene, 3-aminomethylphenyl, 3-aminophenyl, 3-chlorophenyl, 3-cyanophenyl, 3-methoxyphenyl, 3-methylphenyl, 3-nitrophenyl, 4-aminophenyl, 4-chlorophenyl, 4-methoxyphenyl, 4-methylphenyl, 4-nitrophenyl, benzyl, quinolin-8-yl, cyclopropyl, ethyl, isopropyl, methyl, naphthalin-1-yl, naphthalin-2-yl, propyl, pyrid-2-yl, pyrid-3-yl, 3,5-dimethyl-isoxazol-4-yl and 2,4,6-trimethylphenyl.
- 12. A compound selected from the group consisting of:
(Z)-3-{1-[4-(N-(2-aminoethyl)-N-methylsulphonyl-amino)-phenylamino]-1-phenyl-methylidene}-5-phenylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(N-(2-dimethylaminoethyl)-N-phenylsulphonyl-amino)-phenylamino]-1-phenyl-methylidene}-5-phenylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(4-methylpiperazinomethyl)-phenylamino]-1-phenyl-methylidene}-5-phenylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(pyrrolidin-1-ylmethyl)-phenylamino]-1-phenyl-methylidene}-5-phenylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(N-methyl-N-acetyl-amino)-phenylamino]-1-phenyl-methylidene}-5-phenylsulphonylamino-2-indolinone, (Z)-3-(1-phenylamino-1-phenyl-methylidene)-5-phenylsulphonylamino-2-indolinone, (Z)-3-[1-(4-chlorophenylamino)-1-phenyl-methylidene]-5-phenylsulphonylamino-2-5 indolinone, (Z)-3-{1-[4-(N-(2-propionylamino-ethyl)-N-propionyl-amino)-phenylamino]-1-phenyl-methylidene}-5-phenylsulphonylamino-2-indolinone, (Z)-3-[1-(4-dimethylaminomethyl-phenylamino)-1-phenyl-methylidene]-5-phenylsulphonylamino-2-indole, (Z)-3-[1-(4-(N-methyl-N-methylsulphonyl-amino)-phenylamino)-1-phenyl-methylidene]-5-phenylsulphonylamino-2-indolinone, (Z)-3-[1-(4-(N-methyl-N-piperidinomethylcarbonyl-amino)-phenylamino)-1-phenyl-methylidene]-5-phenylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(pyrrolidin-1-ylmethyl)-phenylamino]-1-phenyl-methylidene}-5-1 5 benzylsulphonylamino-2-indolinone, (Z)-3-{1-[4-((2,6-dimethylpiperidino)-methyl)-phenylamino]-1-phenyl-methylidene}-5-(3-nitrophenylsulphonylamino)-2-indolinone, (Z)-3-{1-[4-dimethylaminomethyl-phenylamino]-1-phenyl-methylidene}-5-ethylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(N-benzyl-N-methyl-aminomethyl)-phenylamino]-1-phenyl-methylidene}-5-ethylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(2-dimethylamino-ethyl)-phenylamino]1-phenyl-methylidene}-5-ethylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(pyrrolidin-1-ylmethyl)-phenylamino]-1-phenyl-methylidene}-5-(pyridin-3-ylsulphonylamino)-2-indolinone, (Z)-3-{1-[4-(pyrrolidin-1-ylcarbonyl)-phenylamino]-1-phenyl-methylidene}-5-(pyridin 3-ylsulphonylamino)-2-indolinone, (Z)-3-[1-(4-piperidinomethyl-phenylamino)1-phenyl-methylidene]-5-methylsulphonylamino-2-indolinone (Z)-3-{1-[4-(piperidinomethyl)-phenylamino]-1-phenyl-methylidene}-5-ethylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(piperidinomethyl)-phenylamino]-1-phenyl-methylidene}-5-isopropylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(piperidinomethyl)-phenylamino]-1-phenyl-methylidene}-5-(naphthalin-1-ylsulphonylamino)-2-indolinone, (Z)-3-{1-[4-(piperidinomethyl)-phenylamino]-1-phenyl-methylidene}-5-(3-nitrophenylsulphonylamino)-2-indolinone, (Z)-3-{1-[4-(piperidinomethyl)-phenylamino]-1-phenyl-methylidene}-5-(3,5-dimethylisoxazol-4-ylsulphonylamino)-2-indolinone, (Z)-3-{1-[4-(piperidinomethyl)-phenylamino]-1-phenyl-methylidene}-5-cyclopropylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(piperidinomethyl)-phenylamino]-1-phenyl-methylidene}-5-(pyridin-3-ylphenylsulphonylamino)-2-indolinone, (Z)-3-{1-[4-(pyrrolidin-1-ylmethyl)-phenylamino]-1-phenyl-methylidene}-5-cyclopropylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(pyrrolidin-1-ylmethyl)-phenylamino]-1-phenyl-methylidene}-5-propylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(pyrrolidin-1-ylmethyl)-phenylamino]-1-phenyl-methylidene}-5-ethylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(pyrrolidin-1-ylmethyl)-phenylamino]-1-phenyl-methylidene}-5-methylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(benzylaminocarbonyl)-phenylamino]-1-phenyl-methylidene}-5-phenylsulphonylamino-2-indolinone, (Z)-3-{1-[4-(N-dimethylaminocarbonylmethyl-N-acetyl-amino)-phenylamino]-1-phenyl-methylidene}-5-phenylsulphonylamino-2-indolinone, (Z)-3-[1-(4-piperidinomethyl-phenylamino)-1-phenyl-methylidene]-5-(4-aminophenylsulphonylamino)-2-indolinone, and (Z)-3-{1-[4-(N-(2-dimethylamino-ethyl)-N-methylsulphonyl-amino)-phenylamino)-1-phenyl-methylidene}-5-(N-methyl-N-phenylsulphonyl-amino)-2-indolinone, or a pharmaceutically acceptable salt thereof.
- 13. A pharmaceutical preparation comprising a compound according to claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 and a pharmaceutically acceptable carrier.
- 14. A method for treating a disease characterised by excessive or abnormal cell proliferation which comprises administering a therapeutic amount of a compound according to claim 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.
Priority Claims (1)
Number |
Date |
Country |
Kind |
100 54 019.8 |
Nov 2000 |
DE |
|
RELATED APPLICATIONS
[0001] Benefit of U.S. Provisional Application Serial No. 60/251,055, filed on Dec. 1, 2000 is hereby claimed.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60251055 |
Dec 2000 |
US |