IP Library Granted Patent US 8,324,214
Granted Patent B2
US 8,324,214 · App. 12/905,287 · Granted Dec 4, 2012

1,3-dihydro-2

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Quick Facts
Patent No.
US 8,324,214
App. No.
12/905,287
Granted
Dec 4, 2012
Kind
B2
Abstract

The subject matter of the present invention are compounds corresponding to formula (I): in which: X is an unsubstituted or substituted divalent (C 1 -C 5 )alkylene radical; R I is an —NR 8 R 9 group; or an unsubstituted or substituted piperidin-3-yl or piperidin-4-yl radical; R 2 is a hydrogen atom, a halogen atom, an Alk group or an OAlk group; R 3 is a hydrogen atom, a halogen atom, an Alk group or an OAlk group; R 4 is a hydrogen atom, a halogen atom, an Alk group, a hydroxyl or an OAlk group; and R 5 is a hydrogen atom, a halogen atom, an Alk group, a hydroxyl or an OAlk group.

Claims (69)

1. A compound corresponding to formula (I):

in which:

X represents a bivalent (C 1 -C 5 )alkylene radical that is unsubstituted or substituted once or several times on a carbon atom with a fluorine atom or with a (C 1 -C 3 )alkyl;

R 1 represents:

a group —NR 8 R 9 , or

a piperidin-3-yl or piperidin-4-yl radical that is unsubstituted or substituted once or several times with a (C 1 -C 4 )alkyl, or a (C 3 -C 5 )cycloalkyl, it being possible for the carbon atoms to also be substituted with one or more fluorine atoms;

R 2 represents a hydrogen atom, a halogen atom, an Alk group, or an OAlk group;

R 3 represents a hydrogen atom, a halogen atom, an Alk group, or an OAlk group;

R 4 represents a hydrogen atom, a halogen atom, an Alk group, a hydroxyl, or an OAlk group;

R 5 represents a hydrogen atom, a halogen atom, an Alk group, a hydroxyl, or an OAlk group;

R 6 represents a hydrogen atom, a halogen atom, an Alk group, a hydroxyl, or an OAlk group;

R 7 represents a hydrogen atom, a halogen atom, an Alk group, a hydroxyl, or an OAlk group;

R 8 and R 9 each independently represent a hydrogen atom or a (C 1 -C 4 )alkyl;

or alternatively R 8 and R 9 , together with the nitrogen atom to which they are attached, constitute a heterocyclic radical chosen from: azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, piperazin-1-yl or perhydroazepin-1-yl, the said heterocyclic radical being unsubstituted or substituted once or several times with an amino, a hydroxyl, a (C 1 -C 4 )alkyl, a (C 3 -C 5 )cycloalkyl, or a (C 1 -C 4 )alkoxy, it being possible for the carbon atoms to also be substituted with one or more fluorine atoms; and

Alk represents a (C 1 -C 4 )alkyl that is unsubstituted or substituted once or several times with a fluorine atom,

or such a compound in the form of a base or of an acid addition salt, or an enantiomer or a racemic mixture thereof.

2. A compound according to claim 1 , in which:

X represents a bivalent (C 3 -C 4 ) alkylene radical that is unsubstituted or substituted once or several times on a carbon atom with a fluorine atom or with a (C 1 -C 3 ) alkyl;

R 1 represents:

a group —NR 8 R 9 , or

a piperidin-4-yl radical;

R 2 represents an Alk group or an OAlk group;

R 3 represents a hydrogen atom;

R 4 represents a halogen atom;

R 5 represents a hydrogen atom;

R 6 represents a halogen atom or an OAlk group;

R 7 represents a hydrogen atom, an Alk group, or an OAlk group;

R 8 and R 9 together with the nitrogen atom to which they are attached constitute a heterocyclic radical chosen from: piperidin-1-yl, piperazin-1-yl, the said heterocyclic radical being unsubstituted or substituted once or twice with a fluorine atom, an amino, a hydroxyl, or a methyl;

Alk represents a (C 1 -C 4 )alkyl that is unsubstituted or substituted once or several times with a fluorine atom;

or such a compound in the form of a base or an acid addition salt, or an enantiomer or a racemic mixture thereof.

3. A compound according to claim 1 , in which:

X represents a bivalent trimethylene or tetramethylene radical;

R 1 represents:

a piperidin-1-yl, a piperazin-1-yl, a 4-methylpiperazin-1-yl, or a piperidin-4-yl;

R 2 represents a methyl or a methoxy;

R 3 represents a hydrogen atom;

R 4 represents a fluorine atom;

R 5 represents a hydrogen atom;

R 6 represents a chlorine atom, a methoxy, an isopropoxy, or a difluoromethoxy;

R 7 represents a hydrogen atom, a methyl, or a methoxy;

or such a compound in the form of a base or an acid addition salt, or an enantiomer or a racemic mixture thereof.

4. A compound according to claim 1 , chosen from:

3-(2-fluorophenyl)-1-[(4-isopropoxyphenyl)sulphonyl]-5-methoxy-3-(3-piperazin-1-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-5-methoxy-1-[(3-methoxyphenyl)sulphonyl]-3-(3-piperazin-1-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

1-[(3-chlorophenyl)sulphonyl]-3-(2-fluorophenyl)-5-methoxy-3-(3-piperazin-1-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-1-[(4-isopropoxyphenyl)sulphonyl]-5-methoxy-3-(3-piperidin-1-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-5-methoxy-1-[(3-methoxyphenyl)sulphonyl]-3-(3-piperidin-1-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one, isomer;

1-{[4-(difluoromethoxy)phenyl]sulphonyl}-3-(2-fluorophenyl)-5-methoxy-3-(3-piperidin-1-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

1-[(3-chlorophenyl)sulphonyl]-3-(2-fluorophenyl)-5-methoxy-3-(3-piperidin-1-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-1-[(4-isopropoxyphenyl)sulphonyl]-5-methoxy-3-(4-piperazin-1-ylbutyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-1-[(4-isopropoxyphenyl)sulphonyl]-5-methoxy-3-[3-(4-methylpiperazin-1-yl)propyl]-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-1-[(4-isopropoxyphenyl)sulphonyl]-5-methoxy-3-[4-(4-methylpiperazin-1-yl)butyl]-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-1-[(4-isopropoxyphenyl)sulphonyl]-5-methoxy-3-(3-piperidin-4-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-1-[(4-isopropoxyphenyl)sulphonyl]-5-methoxy-3-(4-piperazin-1-ylbutyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-1-[(4-isopropoxyphenyl)sulphonyl]-5-methyl-3-(3-piperazin-1-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-5-methoxy-1-[(4-methoxy-3-methylphenyl)sulphonyl]-3-(4-piperazin-1-ylbutyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-fluorophenyl)-5-methyl-3-(3-piperazin-1-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-5-methoxy-1-[(4-methoxy-3-methylphenyl)sulphonyl]-3-(3-piperazin-1-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-fluorophenyl)-5-methoxy-3-(3-piperazin-1-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-1-[(4-methoxy-3-methylphenyl)sulphonyl]-5-methyl-3-(3-piperazin-1-ylpropyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-fluorophenyl)-5-methoxy-3-(4-piperazin-1-ylbutyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-1-[(4-isopropoxyphenyl)sulphonyl]-5-methyl-3-[3-(4-methylpiperazin-1-yl)propyl]-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

3-(2-fluorophenyl)-5-methoxy-1-[(4-methoxy-3-methylphenyl)sulphonyl]-3-[4-(4-methylpiperazin-1-yl)butyl)-1,3-dihydro-2H-pyrrolo[3,2-b]pyridin-2-one;

or such a compound in the form of a base or of an acid addition salt, or an enantiomer or a racemic mixture thereof.

5. A method for preparing a compound of formula (I) according to claim 1 , comprising:

reacting a compound of formula:

in which X, R 1 , R 2 , R 3 , R 4 and R 5 are as defined in claim 1 , in the presence of a base, with a sulphonyl halide of formula:

in which R 6 and R 7 are as defined in claim 1 and Hal represents a halogen atom.

6. A pharmaceutical composition comprising a compound of claim 1 and at least one pharmaceutically acceptable excipient.

Assignments (1)
CHANGE OF NAME Recorded Jun 20, 2012
From: SANOFI-AVENTIS
To: SANOFI
Reel/Frame 028413/0927 →