Claims
- 1. A compound of the formula wherein:X denotes an oxygen or sulphur atom, R1 denotes a hydrogen atom, a C1-4-alkoxy-carbonyl or C2-4-alkanoyl group, R2 denotes a carboxy or C1-4-alkoxy-carbonyl group or an aminocarbonyl group optionally substituted by one or two C1-3-alkyl groups, whilst the substituents may be identical or different, R3 denotes a hydrogen atom or a C1-6-alkyl group which may be substituted at the 2 position, in relation to the carbon atom of the R3-C(R4NR5)═ group by a fluorine, chlorine or bromine atom, by a hydroxy, C1-3-alkoxy, C1-3-alkylsulphenyl, C1-3-alkylsulphinyl, C1-3-alkylsulphonyl, phenylsulphenyl, phenylsulphinyl, phenylsulphonyl, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, C2-5-alkanoylamino or N-(C1-3-alkylamino)-C2-5-alkanoylamino group, R4 denotes a phenyl or naphthyl group which is substituted by a C2-3-alkoxy group which is substituted in the 2 or 3 position by a 5- membered cycloalkyleneimino group, by a carbonyl group which is substituted by a 5- membered cycloalkyleneimino group, by a C1-3-alkyl group which is substituted by a 5-membered cycloalkenyleneimino group or by a 4- to 5-membered cycloalkyleneimino group, wherein the abovementioned 5-membered cycloalkyleneimino groups may be substituted by one or two C1-3-alkyl groups, by a C5-7-cycloalkyl or phenyl group, by a C1-3-alkyl, C5-7-cycloalkyl, phenyl, carboxy or C1-4-alkoxy-carbonyl group and by a hydroxy group and in the abovementioned cycloalkyleneimino groups a methylene group adjacent to the nitrogen atom may be replaced by a carbonyl group, or by a C1-3-alkyl group which is substituted by a 5-membered cycloalkyleneimino group, whilst a phenyl group optionally mono- or disubstituted by fluorine, chlorine or bromine atoms or by methyl or methoxy groups, wherein the substituents may be identical or different, may be fused to the abovementioned 5-membered cycloalkyleneimino groups via two adjacent carbon atoms, whilst additionally the abovementioned monosubstituted phenyl groups may be substituted by a fluorine, chlorine or bromine atom or by a methyl, methoxy or nitro group, a 5-membered heteroaromatic group which contains an imino group, and R5 denotes a hydrogen atom or a C1-3-alkyl group whilst any carboxy, amino or imino groups present may be substituted by groups which can be cleaved in vivo, or a pharmaceutically acceptable salt thereof.
- 2. A compound of the formula I according to claim 1, wherein:X denotes an oxygen atom, R1 denotes a hydrogen atom, R2 denotes an aminocarbonyl group, R3 denotes a hydrogen atom or a C1-4-alkyl group which may be substituted, at the 2 position in relation to the carbon atom of the R3-C(R4NR5)═ group, by a chlorine or bromine atom or by a phenylsulphonyl group, R4 denotes a phenyl group which is substituted by a C2-3-alkoxy group which is substituted in the 2 or 3 position by 5- membered cycloalkyleneimino group, by a carbonyl group which is substituted by a 5-membered cycloalkyleneimino group, by a C1-3-alkyl group which is substituted by a 5-membered cycloalkenyleneimino group or by a 4- to 5-membered cycloalkyleneimino group, wherein the abovementioned 5-membered cycloalkyleneimino groups may be substituted by one or two C1-3-alkyl groups, by a cyclohexyl or phenyl group, by a C1-3-alkyl, cyclohexyl, phenyl, carboxy or C1-4-alkoxy-carbonyl group and by a hydroxy group and in the abovementioned cycloalkyleneimino groups a methylene group adjacent to the nitrogen atom may be replaced by a carbonyl group, by a C1-3-alkyl group which is substituted by a 5-membered cycloalkyleneimino group, whilst a phenyl group optionally mono- or disubstituted by fluorine, chlorine or bromine atoms or by methyl or methoxy groups, wherein the substituents may be identical or different, may be fused to the abovementioned 5-membered cycloalkyleneimino groups via two adjacent carbon atoms, whilst additionally the abovementioned monosubstituted phenyl groups may be substituted by a fluorine, chlorine or bromine atom or by a methyl, methoxy or nitro group, R5 denotes a hydrogen atom or a C1-3-alkyl group, or a pharmaceutically acceptable salt thereof.
- 3. A compound of the formula I according to claim 2, wherein:R2 is in the 5 position, or a pharmaceutically acceptable salt thereof.
- 4. A compound of the formula I according to claim 1, wherein:X denotes an oxygen atom, R1 denotes a hydrogen atom, R2 in the 5 position denotes an aminocarbonyl group, R3 denotes a hydrogen atom or a C1-4-alkyl group which may be terminally substituted by a chlorine or bromine atom or by a phenylsulphonyl group, R4 denotes a phenyl group which may be substituted by a methyl or ethyl group, which in each case is substituted by a 5-membered cycloalkenyleneimino group or by a 5-membered cycloalkyleneimino group, whilst the abovementioned 5-membered cycloalkyleneimino groups may be substituted by one or two methyl groups, by a cyclohexyl or phenyl group, by a methyl, cyclohexyl or phenyl group and by a hydroxy group, or by a methyl or ethyl group which may be substituted by a phenyl group which is substituted by a 5-membered cycloalkyleneimino group, whilst additionally a phenyl ring is fused to the abovementioned cycloalkyleneimino groups via 2 adjacent carbon atoms, whilst additionally the abovementioned monosubstituted phenyl groups may be substituted by a fluorine, chlorine or bromine atom or by a methyl, methoxy or nitro group, and R5 denotes a hydrogen atom or a C1-4-alkyl group, or a pharmaceutically acceptable salt thereof.
- 5. A compound of the formula I according to claim 1, wherein:X denotes an oxygen atom, R1 denotes a hydrogen atom, R2 in the 5 position denotes an aminocarbonyl group, R3 denotes a hydrogen atom or a C1-4-alkyl group, R4 denotes a phenyl group which may be substituted by a methyl or ethyl group, which is substituted in each case by a 5-membered cycloalkenyleneimino group or by a 5-membered cycloalkyleneimino group, whilst the abovementioned 5-membered cycloalkyleneimino groups may be substituted by one or two methyl groups, by a cyclohexyl or phenyl group, by a methyl, cyclohexyl or phenyl group and by a hydroxy group, or by a methyl or ethyl group which may be substituted by a phenyl group which is substituted in the 4 position by a 5-membered cycloalkyleneimino group, whilst additionally a phenyl ring is fused to the abovementioned cycloalkyleneimino groups via 2 adjacent carbon atoms, whilst additionally the abovementioned monosubstituted phenyl groups may be substituted by a fluorine, chlorine or bromine atom or by a methyl, methoxy or nitro group, and R5 denotes a hydrogen atom or a C1-4-alkyl group, or a pharmaceutically acceptable salt thereof.
- 6. A compound selected from the group consisting of:(a) 3-Z-[1-(4-pyrrolidinomethyl-phenylamino)-1-methyl-methylene]-5-amido-2-indolinone, (b) 3-Z-[1-[4-(2-ethoxycarbonyl-pyrrolidinomethyl)-phenylamino]-1-methyl-methylene]-5-amido-2-indolinone, (c) 3-Z-[1-[4-(2,5-Dihydropyrrol-1-yl-methyl)-phenylamino]-1-methyl-methylene]-5-amido-2-indolinone, (d) 3-Z-[1-(4-Azetidionomethyl-phenylamino)-1-methyl-methylene]-5-amido-2-indolinone and (e) 3-Z-[1-(4-(1,3-Dihydro-isoindol-2-yl-methyl)-phenylamino)-1-methyl-methylene]-5-amido-2-indolinone, or a pharmaceutically acceptable salt thereof.
- 7. 3-Z-[1-(4-Pyrrolidinomethyl-phenylamino)-1-methyl-methylene]-5-amido-2-indolinone or a pharmaceutically acceptable salt thereof.
- 8. A pharmaceutical composition comprising a compound in accordance with claim 1.
- 9. A method for treating excessive or anomalous cell proliferation which method comprises administering to a host in need of such treatment a cell proliferation-inhibiting amount of a compound in accordance with claim 1, 2, 3, 4, 5, 6 or 7.
- 10. A method for treating lymphoma or solid tumors which method comprises administering to a host in need of such treatment a therapeutic amount of a compound in accordance with claim 1, 2, 3, 4, 5, 6 or 7.
Priority Claims (1)
Number |
Date |
Country |
Kind |
198 24 922 |
Jun 1998 |
DE |
|
RELATED APPLICATIONS
This is a division of Ser. No. 09/323,499, filed Jun. 1, 1999 now U.S. Pat. No. 6,319,918, claiming benefit of prior provisional application Ser. No. 60/092,014, filed on Jul. 8, 1998.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4145422 |
Winn et al. |
Mar 1979 |
A |
Foreign Referenced Citations (4)
Number |
Date |
Country |
838 623 |
Jun 1976 |
BE |
WO 96 40116 |
Dec 1996 |
WO |
WO 98 07695 |
Feb 1998 |
WO |
WO 99 15500 |
Apr 1999 |
WO |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/092014 |
Jul 1998 |
US |