Fast-dissociating dopamine 2 receptor antagonists

Patent metadata

Field	Value
Publication number	US-9422296-B2
Application number	US-201414444968-A
Country	US
Kind code	B2
Filing date	Jul 28, 2014
Priority date	Feb 13, 2007
Publication date	Aug 23, 2016
Grant date	Aug 23, 2016

Abstract

The present invention relates to 4-aryl-6-piperazin-1-yl-3-substituted-pyridazines that are fast dissociating dopamine 2 receptor antagonists, processes for preparing these compounds, pharmaceutical compositions comprising these compounds as an active ingredient. The compounds find utility as medicines for treating or preventing central nervous system disorders, for example schizophrenia, by exerting an antipsychotic effect without motor side effects.

First claim

The invention claimed is:

1. A method of treatment of a disorder selected from the group consisting of schizophrenia, schizophreniform disorder, and schizoaffective disorder, comprising administering a therapeutically effective amount of the compounds of formula (I)

R 1 is trifluoromethyl;
R 2 is selected from the group consisting of phenyl; phenyl substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, cyano, C 1-4 alkyl, C 1-4 alkyloxy, C 1-4 alkylsulfonyl, perfluoroC 1-4 alkyl, diC 1-4 alkylamino, hydroxyl, and phenyl substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo, C 1-4 alkyl and perfluoroC 1-4 alkyl; thienyl; thienyl substituted with 1 or 2 substituents each independently selected from the group consisting of halo and C 1-4 alkyl; naphthyl; pyridinyl; pyrrolyl; benzothiazolyl; indolyl; quinolinyl; C 3-8 cycloalkyl; or C 5-7 cycloalkenyl;
R 3 is hydrogen;
R 4 and R 5 are each independently selected from the group consisting of hydrogen or methyl;
n is 1;
R 6 is selected from the group consisting of hydrogen, ethyl or (3,5-difluorophenyl)methyl; or R 5 and R 6 together form 1,3-propanediyl; or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 wherein the compound is 4-phenyl-6-piperazin-1-yl-3-trifluoromethyl-pyridazine.

3. The method of claim 1 wherein the compound is 4-phenyl-6-piperazin-1-yl-3-trifluoromethyl-pyridazine monohydrochloride.

4. The method of claim 1 wherein the disorder is schizophrenia.

5. The method of claim 1 wherein the disorder is selected from the group consisting of schizophrenia and schizoaffective disorder.

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Macdonald Gregor James
• Langlois Xavier Jean Michel
• Bartolomé-Nebreda José Manuel
• Van Gool Michiel Luc Maria

Classifications

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/28

  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 title