US 7,119,086 B2 · Phenylsulfonyl-1,3-dihydro-2h-indole-2-one derivatives, their preparation and their therapeutic use

Abstract

The invention relates to compounds of formula: and also to the salts thereof with mineral or organic acids, and the solvates and/or hydrates thereof, with affinity for and selectivity towards the arginine-vasopressin V1b receptors and/or for the ocytocin receptors and, furthermore, for certain compounds, affinity for the V1a receptors. The invention also relates to the process for preparing them, to the intermediate compounds of formula (IV) that are useful for preparing them, to pharmaceutical compositions containing them and to their use for preparing medicinal products.

Claims26

Dependent claims

A compound of formula (I):

in which:
n is 1 or 2;
X represents —CH2—;
—O—;
—NH—;
—O—CH2—;
—NH—CH2—;
or —NH—CH2—CH2—;
R1 represents halogen;
a (C1–C4)alkyl;
or (C1–C4)alkoxy;
R2 represents hydrogen;
halogen;
(C1–C4)alkyl;
(C1–C4)alkoxy;
trifluoromethyl;
R3 represents halogen;
(C1–C3)alkyl;
(C1–C3)alkoxy;
trifluoromethyl;
or trifluoromethoxy;
R4 represents hydrogen;
halogen;
(C1–C3)alkyl;
or (C1–C3)alkoxy;
R5 is chosen from:
R6represents (C1–C4)alkoxy;
and
R7 represents (C1–C4)alkoxy;
or a salt or hydrate thereof.

27 more elements

A compound chosen from:

5-chloro-3-(2-ethoxyphenyl)-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-[2-oxo-2-[4-(4-pyridyl)-1-piperazinyl]ethyl]-1,3-dihydro-2H-indol-2-one;
5-chloro-3-(2-isopropoxyphenyl)-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-[2-oxo-2-[4-(4-pyridyl)-1-piperazinyl]ethyl]-1,3-dihydro-2H-indol-2-one;
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(2-pyridyl)-1-piperazinecarboxylate;
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-isopropoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(4-pyridyl)-1-piperazinecarboxylate;
N-[5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-(4-pyridyl)homopiperazine-1-carboxamide;
N-[5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-isopropoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-(3-pyridyl)piperazine-1-carboxamide;
N-[5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-isopropoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-(4-pyridyl)piperazine-1-carboxamide;
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-3-[[3-oxo-3-[4-(2-pyridyl)-1-piperazinyl]propyl]amino]-1,3-dihydro-2H-indol-2-one;
5,6-dichloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-3-[2-oxo-2-[4-(4-pyridyl)-1-piperazinyl]ethyl]-1,3-dihydro-2H-indol-2-one;
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-6-methyl-3-[2-oxo-2-[4-(4-pyridyl)-1-piperazinyl]ethyl]-1,3-dihydro-2H-indol-2-one;
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-6-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(4-pyridyl)-1-piperazinecarboxylate;
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-6-methoxy-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(4-pyridyl)-1-piperazinecarboxylate;
N-[5-chloro-3-(2-chlorophenyl)-1-[(2,4-dimethoxyphenyl)sulphonyl]-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-(2-pyridyl)piperazine-1-carboxamide;
N-[5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-6-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-(4-pyridyl)piperazine-1-carboxamide;
N-[6-chloro-3-(2-chlorophenyl)-1-[(2,4-dimethoxyphenyl)sulphonyl]-5-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-(4-pyridyl)piperazine-1-carboxamide;
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-fluorophenyl)-3-[2-oxo-2-[4-(4-pyridyl)-1-piperazinyl]ethyl]-1,3-dihydro-2H-indol-2-one;
5,6-dichloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-fluorophenyl)-3-[2-oxo-2-[4-(4-pyridyl)-1-piperazinyl]ethyl]-1,3-dihydro-2H-indol-2-one;
5-chloro-3-(2,3-dimethoxyphenyl)-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-[2-oxo-2-[4-(4-pyridyl)-1-piperazinyl]ethyl]-1,3-dihydro-2H-indol-2-one;
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-ethoxyphenyl)-3-[2-oxo-2-[4-(3-pyridyl)-1-piperazinyl]ethyl]-1,3-dihydro-2H-indol-2-one;
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-isopropoxyphenyl)-3-[2-oxo-2-[4-(3-pyridyl)-1-piperazinyl]ethyl]-1,3-dihydro-2H-indol-2-one;
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-isopropoxyphenyl)-3-[2-oxo-2-[4-(4-pyridyl)-1-homopiperazine]ethyl]-1,3-dihydro-2H-indol-2-one;
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-isopropoxyphenyl)-3-[2-oxo-2-[4-(1,3-thiazol-2-yl)-1-piperazinyl]ethyl]-1,3-dihydro-2H-indol-2-one;
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(3-pyridyl)-1-piperazinecarboxylate;
and
5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-ethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl 4-(4-pyridyl)-1-piperazinecarboxylate or a salt or hydrate thereof.

22 more elements

Dependencies are inferred from the claim text.

Facts

Application

10/484,370Filed 15 Jul 2002

Priority

FR 01 1035917 Jul 2001

Published

US 2004/0180878 A116 Sep 2004

Granted

10 Oct 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification57 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics
A61P 1/12
Drugs for disorders of the alimentary tract or the digestive system: antidiarrhoeals

Phenylsulfonyl-1,3-dihydro-2h-indole-2-one derivatives, their preparation and their therapeutic use

Life of this patent

Phenylsulfonyl-1,3-dihydro-2h-indole-2-one derivatives, their preparation and their therapeutic use

Life of this patent

Abstract

Claims26