IP Library › Granted Patent US 7,425,566
Granted Patent B2
US 7,425,566 · App. 11/064,896 · Granted Sep 16, 2008

1,3-dihydro-2H-indol-2-one derivatives, process for preparing them and pharmaceutical compositions containing them

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Quick Facts
Patent No.
US 7,425,566
App. No.
11/064,896
Granted
Sep 16, 2008
Kind
B2
Abstract

The invention relates to compounds of formula: and to solvates and/or hydrates thereof, with affinity for and selectivity towards the V 1b receptors or both the V 1b and V 1a receptors of arginine-vasopressin. The invention also relates to a process for preparing them, to the intermediate compounds of formula (II) which are useful for preparing them, to pharmaceutical compositions containing them and to their use for preparing medicinal products.

Claims (60)

1. A compound of formula (I):

in which:

n is 2;

W represents an oxygen atom or a sulphur atom;

R 1 represents a halogen atom; a (C 1 -C 4 )alkyl; a (C 1 -C 4 )alkoxy; a trifluoromethyl radical; or a trifluoromethoxy radical;

R 2 represents a hydrogen atom; a halogen atom; a (C 1 -C 4 )alkyl; a (C 1 -C 4 )alkoxy; or a trifluoromethyl radical;

or R 2 is in position -6- of the indol-2-one ring;

R 3 represents a halogen atom; a hydroxyl; a (C 1 -C 2 )alkyl; a (C 1 -C 2 )alkoxy; or a trifluoromethoxy radical;

R 4 represents a hydrogen atom; a halogen atom; a (C 1 -C 2 )alkyl; or a (C 1 -C 2 )alkoxy;

or R 3 is in position -2- of the phenyl, R 4 is in position -3- of the phenyl and R 3 and R 4 together represent a methylenedioxy radical;

R 5 represents an ethylamino group; a dimethylamino group; a 1-azetidinyl radical; or a (C 1 -C 2 )alkoxy;

R 6 represents a (C 1 -C 4 )alkoxy; and

R 7 represents a (C 1 -C 4 )alkoxy.

2. A compound according to claim 1 , in the form of an optically pure isomer.

3. A compound according to claim 2 , of formula (Ia):

in which:

the carbon atom bearing the substituent —C(W)R 5 has the (S) configuration and the carbon atom in position -3- of the indol-2-one has either the (R) configuration or the (S) configuration.

4. A compound according to claim 3 , in the form of the laevorotatory isomer.

5. A compound according to claim 1 in which:

n is 2;

W represents an oxygen atom;

R 1 represents a chlorine atom or a methyl radical;

R 2 represents a hydrogen atom or is in position -6- of the indol-2-one and represents a chlorine atom, a methyl radical, a methoxy radical or a trifluoromethyl radical;

R 3 is in position -2- of the phenyl and represents a methoxy radical, a chlorine atom or a fluorine atom;

R 4 represents a hydrogen atom, a methyl radical or a methoxy radical;

or R 3 is in position -2- of the phenyl, R 4 is in position -3- of the phenyl and R 3 and R 4 together represent a methylenedioxy radical;

R 5 represents a dimethylamino group or a methoxy radical;

R 6 is in position -2- of the phenyl and represents a methoxy radical; and

R 7 represents a methoxy radical.

6. A compound chosen from:

(2S)-1-[5,6-Dichloro-1-[(2,4-dimethoxyphenyl)-sulphonyl]-3-(2-chlorophenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethylpiperidine-2-carboxamide, laevorotatory isomer;

(2S)-1-[5,6-Dichloro-1-[(2,4-dimethoxyphenyl)-sulphonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethylpiperidine-2-carboxamide, laevorotatory isomer;

(2S)-1-[5-Chloro-1-[(2,4-dimethoxyphenyl)-sulphonyl]-3-(2-methoxyphenyl)-6-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethylpiperidine-2-carboxamide, laevorotatory isomer; and

(2S)-1-[5-Chloro-1-[(2,4-dimethoxyphenyl)-sulphonyl]-3-(2-methoxyphenyl)-6-trifluoromethyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethylpiperidine-2-carboxamide, laevorotatory isomer.

7. A compound according to claim 3 in which:

n is 2;

W represents an oxygen atom;

R 1 represents a chlorine atom or a methyl radical;

R 2 represents a hydrogen atom or is in position -6- of the indol-2-one and represents a chlorine atom, a methyl radical, a methoxy radical or a trifluoromethyl radical;

R 3 is in position -2- of the phenyl and represents a methoxy radical, a chlorine atom or a fluorine atom;

R 4 represents a hydrogen atom, a methyl radical or a methoxy radical;

or R 3 is in position -2- of the phenyl, R 4 is in position -3- of the phenyl and R 3 and R 4 together represent a methylenedioxy radical;

R 5 represents a dimethylamino group or a methoxy radical;

R 6 is in position -2- of the phenyl and represents a methoxy radical; and

R 7 represents a methoxy radical.

8. A compound according to claim 4 in which:

n is 2;

W represents an oxygen atom;

R 1 represents a chlorine atom or a methyl radical;

R 2 represents a hydrogen atom or is in position -6- of the indol-2-one and represents a chlorine atom, a methyl radical, a methoxy radical or a trifluoromethyl radical;

R 3 is in position -2- of the phenyl and represents a methoxy radical, a chlorine atom or a fluorine atom;

R 4 represents a hydrogen atom, a methyl radical or a methoxy radical;

or R 3 is in position -2- of the phenyl, R 4 is in position -3- of the phenyl and R 3 and R 4 together represent a methylenedioxy radical;

R 5 represents a dimethylamino group or a methoxy radical;

R 6 is in position -2- of the phenyl and represents a methoxy radical; and

R 7 represents a methoxy radical.

9. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient.

10. A pharmaceutical composition comprising a compound according to claim 5 and a pharmaceutically acceptable excipient.

11. A pharmaceutical composition comprising a compound according to claim 6 and a pharmaceutically acceptable excipient.

12. A pharmaceutical composition comprising a compound according to claim 7 and a pharmaceutically acceptable excipient.