Indolin-2-one derivatives, preparation and their use as ocytocin receptor ligands

A compound in the form of a pure enantiomer or of a mixture of enantiomers of formula:

• in which:
• R0 represents a group chosen from:
• in which:
• Z1 represents a chlorine, bromine, iodine or fluorine atom or a (C1-C4)alkyl, (C1-C4)alkoxy or trifluoromethyl group;
• Z2 represents a hydrogen, chlorine, bromine, iodine or fluorine atom or a (C1-C4)alkyl, (C3-C5)cycloalkyl, (C1-C4)alkoxy, (C3-C5)cycloalkoxy or polyfluoro(C1-C4)alkyl group;
• R5 represents T1W in which T1 represents —(CH2)m—, it being possible for m to be equal to 0 or 1, and W represents a hydrogen atom or a hydroxycarbonyl (or carboxyl), (C1-C4)alkoxycarbonyl, 1,3-dioxolan-2-yl or 1,3-dioxan-2-yl group,
• or else W represents an —NR6R7 group in which R6 and R7 represent, independently of one another, a hydrogen atom, a (C1-C4)alkyl group, a (C1-C4)alkylsulphonyl group or a phenylsulphonyl group in which the phenyl group can be mono-, di- or trisubstituted by Z5;
• or else R6 and R7 form, with the nitrogen atom to which they are bonded, a morpholinyl group optionally substituted by a (C1-C4)alkyl group or an oxo;
• or else R6 and R7 form, with the nitrogen atom to which they are bonded, a piperazinyl group optionally substituted in the 4-position by a Z3 substituent;
• or else R6 and R7 form, with the nitrogen atom to which they are bonded, a pyrrolidinyl or piperidyl group, the said pyrrolidinyl and piperidyl groups optionally being substituted by Z4;
• or else W represents an —NR8COR9 group in which R8 represents a hydrogen atom or a (C1-C4)alkyl group and R9 represents a hydrogen atom or a (C1-C4)alkyl, benzyl, pyridyl or phenyl group, it being possible for the said phenyl group to be mono-, di- or trisubstituted by Z5;
• or else R9 represents an —NR10R11 group in which R10 and R11 represent, independently of one another, a hydrogen atom or a (C1-C4)alkyl group or else R10 and R11 form, with the nitrogen atom to which they are bonded, a pyrrolidinyl, piperidyl or morpholinyl group optionally substituted by a (C1-C4)alkyl group;
• or else R9 represents a pyrrolidin-2-yl or -3-yl or piperid-2-yl, -3-yl or 4-yl group, the said pyrrolidinyl and piperidyl groups optionally being substituted by Z7;
• or else R9 represents a —T2—R12 or —T2—COR12 group in which T2 represents —(CH2)n—, it being possible for n to be equal to 1, 2, 3 and 4, and R12 represents a (C1-C4)alkoxy or —NR10R11 group, R10 and R11 being as defined above;
• or else W represents a —CONR13R14 group in which R13 represents a hydrogen atom or a (C1-C4)alkyl, (C3-C7)cycloalkyl, monofluoro(C1-C4)alkyl or polyfluoro(C1-C4)alkyl group and R14 represents a hydrogen atom, a (C1-C4)alkyl group, a phenyl group optionally substituted by Z5, a —T4—R15 group in which T4 represents —(CH2)q—, with q equal to 1, 2, 3 or 4, and R15 represents a hydroxyl group, a (C1-C4)alkoxy group, a (C1-C4)alkoxycarbonyl group, a (C1-C4)alkoxycarbonylamino group, a phenyl group optionally mono- or disubstituted by Z5, a pyrid-2-yl, -3-yl or -4-yl, or an —NR16R17 group in which R16 and R17 represent, independently of one another, a hydrogen atom or a (C1-C4)alkyl group or else R16 and R17 form, with the nitrogen atom to which they are bonded, a morpholinyl group optionally mono- or disubstituted by a (C1-C4)alkyl group or else R16 and R17 form, with the nitrogen atom to which they are bonded, a piperazinyl group optionally substituted in the 4-position by a Z3 substituent or else R16 and R17 form, with the nitrogen atom to which they are bonded, a pyrrolidinyl or piperidyl group, the said pyrrolidinyl and piperidyl groups optionally being substituted by Z5, it being understood that, when q=1, R15 is other than hydroxyl, (C1-C4)alkoxy, (C1-C4)alkoxycarbonylamino or —NR16R17;
• or else R13 and R14 form, with the nitrogen atom to which they are bonded, a morpholinyl group optionally mono- or disubstituted by a (C1-C4)alkyl group or a piperazinyl group optionally substituted in the 4-position by a Z3 substituent;
• or else R13 and R14 form, with the nitrogen atom to which they are bonded, an azetidinyl, pyrrolidinyl, piperidyl or hexahydroazepinyl group, the said pyrrolidinyl, piperidyl and hexahydroazepinyl groups optionally being mono- or disubstituted by Z8;
• or else W represents an OR18 group in which R18 represents a hydrogen atom or a (C1-C4)alkyl, (C1-C4)alkoxy(C1-C4)alkyl or —T3—R19 group in which T3 represents —(CH2)p—, it being possible for p to be equal to 2 or 3, and R19 is chosen from the hydroxyl, triphenylmethoxy or —NR20R21 groups in which R20 represents a hydrogen atom or a (C1-C4)alkyl group and R21 represents a hydrogen atom or a (C1-C4)alkyl, tetrahydrofuranylmethyl or tetrahydropyranylmethyl group, or else R20 and R21 form, with the nitrogen atom to which they are bonded, a morpholinyl group optionally mono- or disubstituted by a (C1-C4)alkyl group or a piperazinyl group optionally substituted in the 4-position by a Z3 substituent, or else R20 and R21 form, with the nitrogen atom to which they are bonded, a pyrrolidinyl or piperidyl group, the said pyrrolidinyl and piperidyl groups optionally being substituted by Z5;
• Z3 represents a (C1-C4)alkyl, pyridyl, phenyl, (C1-C4)alkylcarbonyl or (C1-C4)alkoxycarbonyl group;
• Z4 represents an oxo, a fluorine atom, a hydroxyl, a (C1-C4)alkyl, a benzyl, an amino, a (C1-C4)alkylamino, a di(C1-C4)alkylamino, a (C1-C4)alkoxy, a (C1-C4)alkoxycarbonyl or a (C1-C4)alkoxycarbonylamino;
• Z5 represents a chlorine, bromine, iodine or fluorine atom, a hydroxyl group, a (C1-C4)alkyl group or a (C1-C4)alkoxy group;
• Z7 represents a fluorine atom, a hydroxyl group, a hydroxy(C1-C4)alkyl group, a (C1-C4)alkyl group, a (C1-C4)alkoxy group or a (C1-C4)alkylcarbonyl group;
• Z8 represents a fluorine atom or a hydroxyl, (C1-C4)alkyl, (C3-C6)cycloalkyl, benzyl, amino, (C1-C4)alkylamino, di(C1-C4)alkylamino, (C1-C4)alkoxycarbonyl, (C1-C4)alkoxycarbonylamino, (C3-C6)cycloalkoxy, hydroxycarbonyl, hydroxy(C1-C4)alkyl, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxy or —CONR23R24 group in which R23 and R24 represent, independently of one another, a hydrogen atom, a (C1-C4)alkyl, a monofluoro(C1-C4)alkyl or a polyfluoro(C1-C4)alkyl, or else R23 and R24 form, with the nitrogen atom to which they are bonded, a pyrrolidinyl or piperidyl group, the said pyrrolidinyl or piperidyl groups optionally being substituted by Z3 or a difluoromethylidene;
• Z6 represents a chlorine atom or a (C1-C4)alkyl or (C1-C4)alkoxy group;
• R1 represents a (C1-C4)alkyl group optionally comprising a double or a triple bond, a (C1-C4)alkoxycarbonyl group, a phenyloxycarbonyl group or a T1—R22 group in which T1 is as defined above and R22 represents a hydroxyl or (C1-C4)alkoxy group;
• R2 and R4 represent, independently of one another, a hydrogen, chlorine or fluorine atom or a (C1-C4)alkyl or (C1-C4)alkoxy group;
• R3 represents a chlorine or fluorine atom or a (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)carbamoyl, (C1-C4)alkylcarbonylamino, nitro, cyano, trifluoromethyl, amino, (C3-C6)cycloalkylamino, (C1-C4)alkylamino, di(C1-C4)alkylamino, tri(C1-C4)alkylammonium A−, A− being an anion, pyrrolidin-1-yl, piperid-1-yl, piperazin-1-yl, morpholin-4-yl or hexahydroazepin-1-yl group;
• X and Y represent, independently of one another, a hydrogen, chlorine, bromine, iodine or fluorine atom or a (C1-C4)alkoxy or trifluoromethoxy group;
• or a pharmaceutically acceptable salt, solvate and/or hydrate thereof.