N-[piperazinyl hetaryl]arylsufonamide compounds with affinity for the dopamine D3 receptor

• US 8,476,275 B2
• Filed: 05/27/2011
• Issued: 07/02/2013
• Est. Priority Date: 04/14/2003
• Status: Expired due to Fees

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: Abbott GmbH & Company KG (Abbott Laboratories Incorporated)
• Inventors: Haupt, Andreas, Lubisch, Wilfried, Grandel, Roland, Drescher, Karla, Geneste, Herve, Unger, Liliane, Sauer, Daryl R., Turner, Sean Colm, Braje, Wilfried
• Primary Examiner(s): BERNHARDT, EMILY A
• Application Number:
  US13/117,269
• Publication Number:
  US 20110294817A1
• Time in Patent Office: 767 Days
• Field of Search: None
• US Class Current: 514/252.14
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 25/34 Tobacco-abuse
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 213/76 to which a second hetero atom is attached nitro radicals C07D213/61
• CPC Class Codes: C07D 239/48 Two nitrogen atoms
• CPC Class Codes: C07D 239/50 Three nitrogen atoms
• CPC Class Codes: C07D 403/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/14 : containing three or more hetero rings
• CPC Class Codes: C07D 487/08 : Bridged systems

Abstract

The invention related to N-[(piperazinyl)hetaryl]arylsulfonamide compounds of the general formula (I) in which Q is a bivalent, 6-membered heteroaromatic radical which possesses 1 or 2 N atoms as ring members and which optionally carries one or two substituents R^a which is/are selected, independently of each other, from halogen, CN, NO₂, CO₂R⁴, COR⁵, C₁-C₄-alkyl and C₁-C₄-haloalkyl; Ar is phenyl or a 6-membered heteroaromatic radical which possesses 1 or 2 N atoms as ring members and which optionally carries one or two substituents R^b, which is/are selected from halogen, NO₂, CN, CO₂R⁴, COR⁵, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₄-alkyl and C₁-C₄-haloalkyl, with it also being possible for two radicals R^b which are bonded to adjacent C atoms of Ar to be together C₃-C₄-alkylene; R¹ is hydrogen, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-cycloalkyl, C₃-C₆-cycloalkyl-C₁-C₄-alkyl, C₁-C₄-hydroxyalkyl, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₃-C₄-alkenyl or C₃-C₄-alkynyl; with the radicals n, R¹, R², R³, R⁴ and R⁵ having the meanings given in the patent claims, to the N-oxides and to the physiologically tolerated acid addition salts of these compounds and to pharmaceutical compositions which comprise at least one N-[(piperazinyl)hetaryl]arylsulfonamide compound as claimed in one of claims 1 to 10 and/or at least one physiologically tolerated acid addition salt of I and/or an N-oxide of I, where appropriate together with physiologically acceptable carriers and/or auxiliary substances for treating diseases which respond to influencing by dopamine D₃ receptor antagonists or agonists, in particular for treating diseases of the central nervous system and disturbances of kidney function.

Claims

1. A compound selected from the group consisting of:

N-[6-(4-Allylpiperazin-1-yl)pyridin-3-yl]-4-isopropylbenzenesulfonamide;

N-[6-(4-Allylpiperazin-1-yl)pyridin-3-yl]-4-propylbenzenesulfonamide;

N-[6-(4-Allylpiperazin-1-yl)pyridin-3-yl]-4-butylbenzenesulfonamide;

N-[6-(4-Allylpiperazin-1-yl)pyridin-3-yl]-4-trifluoromethylbenzenesulfonamide;

N-[6-(4-Allylpiperazin-1-yl)pyridin-3-yl]-4-ethylbenzenesulfonamide;

N-[6-(4-Allylpiperazin-1-yl)pyridin-3-yl]-4-vinylbenzenesulfonamide;

4-Isopropyl-N-(6-piperazin-1-ylpyridin-3-yl)benzenesulfonamide;

N-{6-[4-(Cyclohexylmethyl)piperazin-1-yl]pyridin-3-yl}-4-isopropyl-benzenesulfonamide;

N-[6-(4-Isobutylpiperazin-1-yl)pyridin-3-yl]-4-isopropylbenzenesulfonamide;

4-Isopropyl-N-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]benzenesulfonamide;

N-[6-(4-Ethylpiperazin-1-yl)pyridin-3-yl]-4-isopropylbenzenesulfonamide;

N-{6-[4-(Cyclopropylmethyl)piperazin-1-yl]pyridin-3-yl}-4-isopropyl-benzenesulfonamide;

N-[6-(4-Allyl-3-methylpiperazin-1-yl)pyridin-3-yl]-4-isopropylbenzenesulfonamide;

N-{6-[4-Allyl-(3S)-methylpiperazin-1-yl]pyridin-3-yl}-4-isopropylbenzenesulfonamide, S enantiomer;

4-Isopropyl-N-[6-(3-methyl-4-propylpiperazin-1-yl)pyridin-3-yl]benzenesulfonamide;

4-Isopropyl-N-{6-[(3S)-methyl-4-propylpiperazin-1-yl]pyridin-3-yl}benzenesulfonamide, S enantiomer;

N-[5-(4-Allylpiperazin-1-yl)pyridin-2-yl]-4-isopropylbenzenesulfonamide;

N-[2-(4-Allylpiperazin-1-yl)pyrimidin-5-yl]-4-isopropylbenzenesulfonamide;

4-Isopropyl-N-[2-(4-propylpiperazin-1-yl)pyrimidin-5-yl]benzenesulfonamide;

N-[6-(4-Allylpiperazin-1-yl)pyrimidin-4-yl]-4-isopropylbenzenesulfonamide;

N-[2-(4-Allylpiperazin-1-yl)pyridin-5-yl]-4-bromobenzenesulfonamide;

N-[6-(4-Allylpiperazin-1-yl)pyridin-3-yl]-4-cyclopropylbenzenesulfonamide;

4-Isopropyl-N-[2-(4-propylpiperazin-1-yl)pyridin-3-yl]-benzenesulfonamide;

4-Isopropyl-N-[2-(3,5-dimethyl-4-propylpiperazin-1-yl)pyridin-3-yl]-benzenesulfonamide;

N-[2-(4-Allyl-3-methylpiperazin-1-yl)pyridin-3-yl]-4-trifluoromethylbenzenesulfonamide;

N-[6-(4-Allyl-3,5-dimethylpiperazin-1-yl)pyridin-3-yl]-4-isopropylbenzenesulfonamide;

N-[6-(4-Allyl-3,5-dimethylpiperazin-1-yl)pyridin-3-yl]-4-trifluoromethylbenzenesulfonamide;

N-[6-(4-Allylpiperazin-1-yl)pyridin-3-yl]-4-trifluoromethylbenzenesulfonamide;

4-Bromo-N-[6-(4-propylpiperazin-1-yl)pyridin-3-yl]-benzenesulfonamide;

4-Chloro-N-[6-(4-propylpiperazin-1 yl)pyridin-3-yl]-benzenesulfonamide;

4-Isopropyl-N-[6-(5-propyl-2,5-diazabicyclo[2.2.1]hept-2-yl)pyridin-3-yl]-benzenesulfonamide;

N-[6-(5-Allyl-2,5-diazabicyclo[2.2.1]hept-2-yl)pyridin-3-yl]-4-isopropylbenzenesulfonamide;

N-[6-(4-Propylpiperazin-1-yl)pyridin-3-yl]-4-vinylbenzenesulfonamide;

N-{6-[4-(3-Fluoropropyl)piperazin-1-yl]pyridin-3-yl}-4-isopropylbenzenesulfonamide;

4-Isopropyl-N-[6-(4-prop-2-yn-1-ylpiperazin-1-yl)pyridin-3-yl]-benzenesulfonamide;

4-Ethyl-N-[6-(4-propylpiperazin-1-yl)pyridin-3-yl]-benzenesulfonamide;

N-[6-(4-Allylpiperazin-1-yl)pyridin-3-yl]-4-chlorobenzenesulfonamide;

4-Isopropyl-N-(4-methyl-6-piperazin-1-ylpyridin-3-yl)-benzenesulfonamide;

N-[6-(4-Allylpiperazin-1-yl)-4-methylpyridin-3-yl]-4-isopropylbenzenesulfonamide;

4-Isopropyl-N-[4-methyl-6-(4-propylpiperazin-1-yl)pyridin-3-yl]-benzenesulfonamide;

N-[4-Methyl-6-(4-propylpiperazin-1-yl)pyridin-3-yl]-4-vinylbenzenesulfonamide;

N-[6-(4-Butylpiperazin-1-yl)pyridin-3-yl]-4-isopropylbenzenesulfonamide;

N-{6-[(3S)-4-Ethyl-3-methylpiperazin-1-yl]pyridin-3-yl}-4-isopropylbenzenesulfonamide;

N-[2-(4-Allylpiperazin-1-yl)pyridin-5-yl]-4-(N-pyrrolidinyl)benzenesulfonamide;

4-Isopropyl-[N-[2-(4-allylpiperazin-1-yl)-6-methylpyridin-5-yl]-4-(N-pyrrolidinyl)benzenesulfonamide;

4-tert-Butyl-[N-[2-(4-allylpiperazin-1-yl)-6-methylpyridin-5-yl]-benzenesulfonamide;

4-tert-pentyl-[N-[2-(4-allylpiperazin-1-yl)-6-methylpyridin-5-yl]-benzenesulfonamide;

4-Ethyl-N-[6-((S)-3-methyl-4-propyl-piperazin-1-yl)-pyridin-3-yl]-benzenesulfonamide;

N-[6-((S)-3-methyl-4-propyl-piperazin-1-yl)-pyridin-3-yl]-4-vinylbenzenesulfonamide;

N-[6-((S)-4-Allyl-3-methyl-piperazin-1-yl)-2-methoxy-pyridin-3-yl]-4-isopropyl-benzenesulfonamide;

4-Isopropyl-N-[2-methoxy-6-((S)-3-methyl-4-propyl-piperazin-1-yl)-pyridin-3-yl]-benzenesulfonamide;

N-[6-((S)-4-Allyl-3-ethyl-piperazin-1-yl)-pyridin-3-yl]-4-isopropylbenzenesulfonamide;

N-[6-((S)-3-Ethyl-4-propyl-piperazin-1-yl)-pyridin-3-yl]-4-isopropylbenzenesulfonamide;

4-Isopropyl-N-(2-piperazin-1-yl-pyrimidin-5-yl)-benzenesulfonamide;

N-[2-(4-Ethyl-piperazin-1-yl)-pyrimidin-5-yl]-4-isopropyl-benzenesulfonamide;

N-[2-((S)-4-Ethyl-3-methyl-piperazin-1-yl)-pyrimidin-5-yl]-4-isopropyl-benzenesulfonamide;

N-[2-((S)-4-Allyl-3-methyl-piperazin-1-yl)-pyrimidin-5-yl]-4-isopropylbenzenesulfonamide;

4-Isopropyl-N-[2-((S)-3-methyl-4-propyl-piperazin-1-yl)-pyrimidin-5-yl]-benzenesulfonamide;

4-Ethyl-N-[2-((S)-3-methyl-4-propyl-piperazin-1-yl)-pyrimidin-5-yl]-benzenesulfonamide;

N-[2-((S)-3-Methyl-4-propyl-piperazin-1-yl)-pyrimidin-5-yl]-4-vinyl-benzenesulfonamide;

4-Isopropyl-benzenesulfonic acid 6-(4-allyl-piperazin-1-yl)-pyridin-3-yl ester; and

,

4-Isopropyl-benzenesulfonic acid 6-(4-propyl-piperazin-1-yl)-pyridin-3-yl ester;

or a physiologically tolerated acid addition salt thereof, or an N-oxide thereof.

3. A pharmaceutical composition comprising a compound as claimed in claim 1, a physiologically tolerated acid addition salt thereof, or an N-oxide thereof, and a physiologically acceptable carrier and/or an auxiliary substance.

2. A compound that is N-[6-(4-allylpiperazin-1-yl)pyridin-3-yl]-4-isopropylbenzenesulfonamide, a physiologically tolerated acid addition salt thereof, or an N-oxide thereof.