Substituted oxindole derivatives, medicaments containing the latter and use thereof

1. A compound of the formula (I)

in which

A is phenyl or naphthalene, each of which can be substituted by one, two, three or four radicals R 4 which are selected independently of one another from the group consisting of hydrogen, chlorine, bromine, iodine, fluorine, (CH 2 ) 0-2 —CN, CF 3 , OCF 3 , CONH 2 , CONH(C 1 -C 4 -alkyl), CON(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NHCHO, NHCONH 2 , NH(C 0 -C 4 -alkylene)CONH 2 , NH(C 0 -C 4 -alkylene)CONH(C 1 -C 4 -alkyl), NHCOCH 3 , NO 2 , (CH 2 ) 0-2 —OH, O—C 1 -C 6 -alkyl, (CH 2 ) 1-2 —O—C 1 -C 4 -alkyl, O—C 0 -C 4 -alkylene-phenyl, phenyl, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl,

B is an aromatic or partially aromatic monocyclic or bicyclic system which may be composed of 6, 7, 8, 9 or 10 C atom members and which may be substituted by one, two, three or four radicals selected from the group consisting of the radicals R 6 , R 7 , R 8 and R 9 , where R 6 , R 7 , R 8 and R 9 are selected, independently of one another and independently of their respective occurrence, from the group consisting of hydrogen, chlorine, bromine, iodine, fluorine, (CH 2 ) 0-2 —CN, CF 3 , OCF 3 , CONH 2 , CONH(C 1 -C 4 -alkyl), CON(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NHCHO, NH(C 0-4 -alkylene)CONH(C 1 -C 4 -alkyl), NHCOCH 3 , NO 2 , OH, O—C 1 -C 4 -alkyl, (CH 2 ) 0-2 —O—(CH 2 ) 0-3 —CH 3 , O—C 0 -C 4 -alkylene-phenyl, phenyl, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl;

R 1 is CN;

R 2 is hydrogen;

R 3 is a radical (W)—(X)—(Y)—Z, where

W is C 1 -C 4 -alkylene, (C 0 -C 4 -alkylene)-O—(C 0 -C 4 -alkylene) or (C 0 -C 4 -alkylene)-NR 5 —(C 0 -C 4 -alkylene), in which R 5 is hydrogen or C 1 -C 4 -alkyl,

X is CO, SO 2 , (C═NH) or (C═N—CN);

Y is a radical selected from the group consisting of the radicals

Z is a radical selected from the group consisting of the radicals

where

A 2 and A 3 independently of one another are N or C;

A 1 is N, C, O or S;

D 1 , D 2 , D 3 , D 4 and D 5 independently of one another are C or N, but where at least one of the variables D 1 , D 2 , D 3 , D 4 and D 5 is N,

and where Z may in each case be substituted by the radicals R 12 , R 13 and R 14 , where R 12 , R 13 and R 14 have independently of one another the meanings mentioned below, namely

R 12 is hydrogen, chlorine, fluorine CN, CF 3 , OCF 3 , CONH 2 , NHCOCH 3 , NO 2 , OH, O—C 1 -C 4 -alkyl, C 1 -C 4 -alkyl, NH 2 , NH(C 1 -C 4 -alkyl) or N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl);

R 13 is hydrogen, chlorine, fluorine, OCH, or C 1 -C 4 -alkyl;

R 14 is hydrogen;

or a tautomeric, enantiomeric or diastereomeric form, or a physiologically tolerated salt of said compound.

2. The compound of formula (I) according to claim 1 , in which R 1 , R 2 and R 3 have the meanings stated in claim 1

and

A is a phenyl ring which may be substituted by one or two radicals R 4 , where R 4 independently of one another have the meanings stated in claim 1 ;

B is a phenyl ring which may be substituted by one, two, three or four radicals selected from the group consisting of the radicals R 6 , R 7 , R 8 and R 9 , where R 6 , R 7 , R 8 and R 9 independently of one another and independently of their respective occurrence have the meanings stated in claim 1 ;

or a tautomeric, enantiomeric or diastereomeric form, or a physiologically tolerated salt of said compound.

3. The compound of formula (I) according to claim 1 , in which

A is a phenyl ring which may be substituted by one or two radicals R 4 which are selected independently of one another from the group consisting of hydrogen, chlorine, O—C 1 -C 4 -alkyl, (CH 2 ) 1-2 —O—(CH 2 ) 0-2 —CH, and C 1 -C 6 -alkyl,

B is a phenyl ring which may be substituted by one, two, three or four radicals selected from the group consisting of the radicals R 6 , R 7 , R 8 and R 9 , where R 6 , R 7 , R 8 and R 9 are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, fluorine, chlorine, CN, NO 2 , O—C 1 -C 4 -alkyl, (CH 2 ) 1-2 —O—(CH 2 ) 0-2 —CH, and C 1 -C 6 -alkyl,

R 1 is CN and is located in position 5 of the oxindole of the formula (I),

R 2 is hydrogen,

R 3 is a radical (W)—(X)—(Y)—Z, where

W is O, CH 2 NH, NHCH 2 , OCH 2 , CH 2 O or NH,

X is CO, (C═NH) or (C═N—CN),

Y is a radical selected from the group consisting of the radicals

Z is a radical selected from the group consisting of the radicals

where

A 2 and A 3 independently of one another are N or C;

A 1 is N, C, O or S;

D 1 , D 2 , D 3 , D 4 and D 5 independently of one another are C or N, but where at least one of the variables D 1 , D 2 , D 3 , D 4 or D 5 is N,

and where

Z may in each case additionally be substituted by the radicals R 12 , R 13 and R 14 , where R 12 , R 13 and R 14 independently of one another have the meanings stated below, namely

R 12 is hydrogen, chlorine, fluorine, CN, CF 3 , OCF 3 , CONH 2 , NHCOCH 3 , NO 2 , OH, O—C 1 -C 4 -alkyl, C 1 -C 4 -alkyl, NH 2 , NH(C 1 -C 4 -alkyl) or N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl);

R 13 is hydrogen, chlorine, fluorine, OCH 3 or C 1 -C 4 -alkyl;

R 14 is hydrogen;

or a tautomeric, enantiomeric or diastereomeric form, or a physiologically tolerated salt of said compound.

4. The compound of formula (I) according to claim 1 , in which

A is a phenyl ring which may be substituted by one radical R 4 , where R 4 is chlorine, O—C 1 -C 4 -alkyl, or C 1 -C 6 -alkyl;

B is a phenyl ring which may be substituted by one or two radicals selected from the group consisting of the radicals R 6 and R 7 , where R 6 and R 7 are independently of one another and independently of their respective occurrence selected from the group consisting of hydrogen, fluorine, chlorine, CN, NO 2 , O—C 1 -C 4 -alkyl and C 1 -C 6 -alkyl;

R 1 is CN and is located in position 5 of the oxindole of the formula (I);

R 2 is hydrogen;

R 3 is a radical (W)—(X)—(Y)—Z, where

W is O, CH 2 or NH,

X is CO, (C═NH) or (C═N—CN),

Y is a radical selected from the group consisting of the radicals

Z is a radical selected from the group consisting of the radicals

where

A 2 and A 3 independently of one another are N or C;

A 1 is N, C, O or S;

D 1 , D 2 , D 3 , D 4 and D 5 independently of one another are C or N, but where at least one of the variables D 1 , D 2 , D 3 , D 4 and D 5 is N,

and where

Z may in each case be substituted by the radicals R 12 , R 13 and R 14 , where R 12 , R 13 and R 14 independently of one another have the meanings stated below, namely

R 12 is hydrogen, chlorine, fluorine, CN, CF 3 , OCF 3 , CONH 2 , NHCOCH 3 , NO 2 , OH, O—C 1 -C 4 -alkyl, C 1 -C 4 -alkyl, NH 2 , NH(C 1 -C 4 -alkyl) or N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl);

R 13 is hydrogen, fluorine, chlorine, OCH 3 or C 1 -C 4 -alkyl;

R 14 is hydrogen;

or a tautomeric, enantiomeric or diastereomeric form, or a physiologically tolerated salt of said compound.

5. The compound of formula (I) according to claim 1 , in which

A is a phenyl ring which may be substituted by R 4 , where R 4 is chlorine, OCH 2 CH 3I OCH(CH 3 ) 2 , OCH 2 CH 2 CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , or CH 2 CH 2 CH 3 ,

B is a phenyl ring which may be substituted by one or two radicals selected from the group consisting of the radicals R 6 and R 7 , where R 6 and R 7 are independently of one another and independently of their respective occurrence selected from the group consisting of hydrogen, fluorine, chlorine, CN, NO 2 , O—C 1 -C 4 -alkyl, and C 1 -C 6 -alkyl;

R 1 is CN and is located in position 5 of the oxindole of the formula (I);

R 2 is hydrogen;

R 3 is a radical (W)—(X)—(Y)—Z, where

W is CH 2 , O or NH,

X is CO or (C═NH),

Y is the radical

Z is a radical selected from the group consisting of the radicals pyridyl, pyrimidinyl, pyrazinyl, thiazolyl, isoxazolyl, imidazolyl and phthalazinyl

and where

Z in each case is substituted by R 12 and R 13 , where R 12 and R 13 independently of one another have the meanings stated below, namely

R 12 is hydrogen, chlorine, fluorine, CN, CF 3 , OCF 3 , OH, OC 1 -C 4 -alkyl, C 1 -C 4 -alkyl, NH 2 , NH(C 1 -C 4 -alkyl) or N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl);

R 13 is hydrogen, fluorine or C 1 -C 4 -alkyl;

or a tautomeric, enantiomeric or diastereomeric form, or a physiologically tolerated salt of said compound.

6. The compound of formula (I) according to claim 1 , in which

A is a phenyl ring which is substituted by O—CH 2 CH 3 in the ortho position,

B is a phenyl ring which is substituted by one or two radicals selected from the group consisting of the radicals R 6 and R 7 , where R 6 and R 7 are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, fluorine, chlorine, CN, NO 2 , O—C 1 -C 4 -alkyl, and C 1 -C 6 -alkyl,

R 1 is CN and is located in position 5 of the oxindole of the formula (I),

R 2 is hydrogen,

R 3 is a radical (W)—(X)—(Y)—Z, where

W is CH 2 , O or NH,

X is CO or (C═NH),

Y is a radical

Z is a radical selected from the group consisting of the radicals

and where Z may in each case be substituted by the radicals R 12 and R 13 , where R 12 and R 13 independently of one another have the meanings stated below, namely

R 12 is hydrogen, chlorine, fluorine, CN, CF 3 , OCF 3 , OH, OCH 3 , CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , NH 2 , NHCH 3 or N(CH 3 ) 2 ;

R 13 is hydrogen, chlorine, fluorine or CH 3 , CH 2 CH 3 ;

or a tautomeric, enantiomeric or diastereomeric, or a physiologically tolerated salt of said compound.

7. The compound according to claim 1 , having a binding affinity Ki for the vasopressin V1b receptor subtype of less than about 100 nM.

8. The compound of formula (I) according to claim 1 , selected from the group consisting of:

5-Cyano-1-(2,4-dimethoxybenzenesulfonyl)-3-(2-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(6-methylpyridin-2-yl)piperazine-1-carboxylate;

5-Cyano-1-(2-methoxybenzenesulfonyl)-3-(2-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(pyridin-4-yl)piperazine-1-carboxylate;

5-Cyano-1-(2,4-dimethoxybenzenesulfonyl)-3-(2-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(pyridin-4-yl)piperazine-1-carboxylate;

5-Cyano-1-(2-methoxybenzenesulfonyl)-3-(2-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(thiazol-2-yl)piperazine-1-carboxylate;

5-Cyano-1-(2-methoxybenzenesulfonyl)-3-(2-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(5-cyanopyridin-2-yl)piperazine-1-carboxylate;

5-Cyano-1-(4-chlorobenzenesulfonyl)-3-(2-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(5-cyanopyridin-2-yl)piperazine-1-carboxylate;

5-Cyano-1-(2,4-difluorobenzenesulfonyl)-3-(2-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(pyridin-4-yl) piperazine-1-carboxylate;

5-Cyano-1-(2-fluorobenzenesulfonyl)-3-(2-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(pyridin-4-yl) piperazine-1-carboxylate;

5-Cyano-1-benzenesulfonyl-3-(2-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(pyridin-4-yl)-piperazine-1-carboxylate;

4-(Pyridin-4-yl)piperazine-1-[1-(2-methoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(Pyridin-4-yl)piperazine-1-[1-benzenesulfonyl-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(Pyridin-4-yl)piperazine-1-[1-(2-fluorobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(Pyridin-4-yl)piperazine-1-[1-(2,4-difluorobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(Pyridin-4-yl)piperazine-1-[1-(4-cyanobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(Pyridin-4-yl)piperazine-1-[1-(2-methoxy-4-methylbenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(Pyridin-4-yl)piperazine-1-[1-(2,4-dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(Pyridin-4-yl)piperazine-1-[1-(4-nitrobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

1-(4-Cyanobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(pyridin-4-yl) piperazine-1-carboxylate;

1-(4-Nitrobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(pyridin-4-yl) piperazine-1-carboxylate;

[1-(2-Methoxy-4-methylbenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(pyridin-4-yl)piperazine-1-carboxylate;

1-(4-Fluorobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(pyridin-4-yl) piperazine-1-carboxylate;

1-(2,4-Dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(3-cyanopyridin-2-yl) piperazine-1-carboxylate;

1-(2,4-Dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(3-methylpyridin-2-yl) piperazine-1-carboxylate;

1-(2,4-Dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(4-methylpyridin-2-yl) piperazine-1-carboxylate;

1-(2,4-Dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(pyridin-2-yl) piperazine-1-carboxylate;

1-(2,4-Dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(4-cyanopyridin-2-yl) piperazine-1-carboxylate;

1-(2,4-Dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(pyrimidin-2-yl) piperazin-1-carboxylate;

1-(2,4-Dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(4,6-dimethylpyrimidin-2-yl)piperazine-1-carboxylate;

1-(2,4-Dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(pyrazin-2-yl)piperazine-1-carboxylate;

1-(2,4-Dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(thiazol-2-yl) piperazine-1-carboxylate;

4-(Thiazol-2-yl) piperazine-1-[1-(2,4-dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(3-Methylpyridin-2-yl) piperazine-1-[1-(2,4-dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(5-Cyanopyridin-2-yl)piperazine-1-[1-(2,4-dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(Pyrimidin-2-yl)piperazine-1-[1-(2,4-dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(Pyrazin-2-yl) piperazine-1-[1-(2,4-dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(Pyridin-4-yl)piperazine-1-[1-(2,4-dimethoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

1-(2-Fluorobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(5-cyanopyridin-2-yl)piperazine-1-carboxylate;

1-(2,4-Difluorobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(5-cyanopyridin-2-yl)piperazine-1-carboxylate;

1-(2-Fluorobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(thiazol-2-yl) piperazine-1-carboxylate;

1-(2,4-Difluorobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(thiazol-2-yl) piperazine-1-carboxylate;

1-(4-Chlorobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(thiazol-2-yl) piperazine-1-carboxylate;

1-(4-Cyanobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl 4-(thiazol-2-yl) piperazine-1-carboxylate;

4-(5-Cyanopyridin-2-yl)piperazine-1-[1-(4-nitrobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(5-Cyanopyridin-2-yl)piperazine-1-[1-(2,4-difluorobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(5-Cyanopyridin-2-yl)piperazine-1-[1-(2-methoxybenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(5-Cyanopyridin-2-yl)piperazine-1-[1-(4-chlorobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(5-Cyanopyridin-2-yl)piperazine-1-[1-(4-cyanobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(5-Cyanopyridin-2-yl)piperazine-1-[1-benzenesulfonyl-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide;

4-(5-Cyanopyridin-2-yl)piperazin-1-[1-(2-fluorobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide; and

4-(5-Cyanopyridin-2-yl)piperazine-1-[1-(4-cyanobenzenesulfonyl)-5-cyano-2-oxo-3-(2-ethoxyphenyl)-2,3-dihydro-1H-indol-3-yl]carboxamide.

9. A composition comprising at least one compound of the formula (I) according to claim 1 and a pharmaceutically acceptable carrier.

10. A method for the treatment of arterial hypertension or congestive heart failure (CHF) diseases in a mammal in need of such treatment comprising administering to said mammal an effective amount of at least one compound of the formula (I) according to claim 1 .