BENZENESULFONAMIDE COMPOUNDS SUITABLE FOR TREATING DISORDERS THAT RESPOND TO MODULATION OF THE DOPAMINE D3 RECEPTOR
The invention relates to compounds of the formula R 1 is selected from the group consisting of hydrogen, linear C 1 -C 3 alkyl and fluorinated linear C 1 -C 3 alkyl; R 2 is hydrogen or methyl; R 3 is selected from the group consisting of hydrogen, halogen, C 1 -C 2 -alkyl, fluorinated C 1 -C 2 -alkyl, C 1 -C 2 -alkoxy and fluorinated C 1 -C 2 -alkoxy, R 4 is C 1 -C 2 -alkyl or fluorinated C 1 -C 2 -alkyl; n is 0, 1 or 2, and the physiologically tolerated salts of these compounds and the N-oxides thereof. The invention also relates to a pharmaceutical composition that comprises at least one compound of the formula I and/or at least one physiologically tolerated acid addition salt thereof, and further to a method for treating disorders that respond beneficially to dopamine D 3 receptor antagonists or dopamine D 3 agonists, said method comprising administering an effective amount of at least one compound or physiologically tolerated acid addition salt of the formula I to a subject in need thereof.
1 . A N-(6-piperazin-1-ylpyridin-3-yl)benzenesulfonamide compounds of the formula I
wherein
R 1 is selected from the group consisting of hydrogen, linear C 1 -C 3 alkyl and fluorinated linear C 1 -C 3 alkyl;
R 2 is hydrogen or methyl;
R 3 is selected from the group consisting of hydrogen, halogen, C 1 -C 2 -alkyl, fluorinated C 1 -C 2 -alkyl, C 1 -C 2 -alkoxy and fluorinated C 1 -C 2 -alkoxy,
R 4 is C 1 -C 2 -alkyl or fluorinated C 1 -C 2 -alkyl;
N is 0, 1 or 2;
and the physiologically tolerated salts of these compounds and the N-oxides thereof.
2 . The compound as claimed in claim 1 , wherein R 1 is hydrogen.
3 . The compound as claimed in claim 1 or 2 , wherein R 2 is methyl.
4 . The compound as claimed in claim 3 , wherein the carbon atom that carries R 2 has S-configuration.
5 . The compound as claimed in claim 3 , wherein the carbon atom that carries R 2 has R-configuration.
6 . The compound as claimed in claim 1 or 2 , wherein R 2 is hydrogen.
7 . The compound as claimed in any of the preceding claims, wherein R 3 is methyl.
8 . The compound as claimed in any of the preceding claims, wherein R 4 is methyl.
9 . The compound as claimed in claim 8 , wherein the carbon atom that carries R 4 has S-configuration.
10 . The compound as claimed in claim 8 , wherein the carbon atom that carries R 4 has R-configuration.
11 . The compound as claimed in any of the preceding claims, wherein n is 1.
12 . The compound as claimed in any of the preceding claims, wherein n is 2.
13 . The compounds according to claim 1 , selected from the group consisting of:
4-(2-Fluoro-1-methyl-ethyl)-N-[2-methyl-6-(3-methyl-piperazin-1-yl)-pyridin-3-yl]benzenesulfonamide
4-((R)-2-Fluoro-1-methyl-ethyl)-N-[2-methyl-6-((R)-3-methyl-piperazin-1-yl)pyridin-3-yl]-benzenesulfonamide
4-((S)-2-Fluoro-1-methyl-ethyl)-N-[2-methyl-6-((S)-3-methyl-piperazin-1-yl)pyridin-3-yl]-benzenesulfonamide,
4-((R)-2-Fluoro-1-methyl-ethyl)-N-[2-methyl-6-((S)-3-methyl-piperazin-1-yl)pyridin-3-yl]-benzenesu Ifonamide
4-((S)-2-Fluoro-1-methyl-ethyl)-N-[2-methyl-6-((R)-3-methyl-piperazin-1-yl)pyridin-3-yl]-benzenesu Ifonamide
4-(2-Fluoro-1-methyl-ethyl)-N-[2-methyl-6-piperazin-1-yI-pyridin-3-yl]benzenesulfonamide
4-((R)-2-Fluoro-1-methyl-ethyl)-N-[2-methyl-6-piperazin-1-yl-pyridin-3-yl]benzenesulfonamide
4-((S)-2-Fluoro-1-methyl-ethyl)-N-[2-methyl-6-piperazin-1-yl-pyridin-3-yl]benzenesulfonamide
and the physiologically tolerated salts of these compounds.
14 . The compounds according to claim 1 , selected from the group consisting of:
4-(2,2-Difluoro-1-methyl-ethyl)-N-(2-methyl-6-piperazin-1-yI-pyridin-3-yl) benzenesulfonamide
4-((S)-2,2-Difluoro-1-methyl-ethyl)-N-(2-methyl-6-piperazin-1-yI-pyridin-3-yl) benzenesulfonamide
4-((R)-2,2-Difluoro-1-methyl-ethyl)-N-(2-methyl-6-piperazin-1-yI-pyridin-3-yl) benzenesulfonamide
and the physiologically tolerated salts of these compounds.
15 . The compounds according to claim 1 , selected from the group consisting of:
4-(2,2,2-Trifluoro-1-methyl-ethyl)-N-(2-methyl-6-piperazin-1-yl-pyridin-3-yl) benzenesulfonamide
4-((R)-2,2,2-Trifluoro-1-methyl-ethyl)-N-(2-methyl-6-piperazin-1-yl-pyridin-3-yl) benzenesulfonamide
4-((S)-2,2,2-Trifluoro-1-methyl-ethyl)-N-(2-methyl-6-piperazin-1-yl-pyridin-3-yl) benzenesulfonamide
and the physiologically tolerated salts of these compounds.
16 . The compounds according to claim 1 , selected from the group consisting of:
4-(2-Fluoro-1-methyl-ethyl)-N-(2-methoxy-6-piperazin-1-yl-pyridin-3-yl) benzenesulfonamide
4-((R)-2-Fluoro-1-methyl-ethyl)-N-(2-methoxy-6-piperazin-1-yl-pyridin-3-yl) benzenesulfonamide
4-((S)-2-Fluoro-1-methyl-ethyl)-N-(2-methoxy-6-piperazin-1-yl-pyridin-3-yl) benzenesulfonamide
4-(2,2-Difluoro-1-methyl-ethyl)-N-(2-methoxy-6-piperazin-1-yl-pyridin-3-yl) benzenesulfonamide
4-((S)-2,2-Difluoro-1-methyl-ethyl)-N-(2-methoxy-6-piperazin-1-yl-pyridin-3-yl) benzenesulfonamide
4-((R)-2,2-Difluoro-1-methyl-ethyl)-N-(2-methoxy-6-piperazin-1-yl-pyridin-3-yl) benzenesulfonamide
N-(2-Methoxy-6-piperazin-1-yl-pyridin-3-yl)-4-(2,2,2-trifluoro-1-methyl-ethyl) benzenesulfonamide
N-(2-Methoxy-6-piperazin-1-yl-pyridin-3-yl)-4-((S)-2,2,2-trifluoro-1-methyl-ethyl) benzenesulfonamide
N-(2-Methoxy-6-piperazin-1-yl-pyridin-3-yl)-4-((R)-2,2,2-trifluoro-1-methyl-ethyl) benzenesulfonamide
and the physiologically tolerated salts of these compounds.
17 . A pharmaceutical composition comprising at least one compound as claimed in any of claims 1 to 16 , optionally together with at least one physiologically acceptable carrier or auxiliary substance.
18 . The use of a compound as claimed in any of claims 1 to 16 for preparing a medicament.
19 . A compound as claimed in any of claims 1 to 16 for the use as a medicament.
20 . The use of a compound as claimed in any of claims 1 to 16 for treating a medical disorder susceptible to treatment with a dopamine D 3 receptor ligand.
21 . The use of a compound as claimed in any of claims 1 to 16 for preparing a medicament for treating a medical disorder susceptible to treatment with a dopamine D 3 receptor ligand.
22 . A method for treating a medical disorder susceptible to treatment with a dopamine D 3 receptor ligand, said method comprising administering an effective amount of at least one compound as claimed in any of claims 1 to 16 to a subject in need thereof.
23 . A method for treating a disorder of the central nervous system, said method comprising administering an effective amount of at least one compound as claimed in any of claims 1 to 16 to a subject in need thereof.
24 . The method as claimed in claim 22 or 23 , wherein the medical disorder is schizophrenia.
25 . The method as claimed in claim 22 or 23 , wherein the medical disorder is drug addiction.
26 . The method as claimed in claim 22 , wherein the medical disorder is diabetic nephropathy.
27 . The method as claimed in claim 22 or 23 , wherein the medical disorder is bipolar disorder.
28 . A compound of the formula IV
wherein R a is an N-protecting group and wherein n, R 2 , R 3 and R 4 are as defined in claims 1 to 12 .