Aza-bicycloalkyl ethers and their use as alpha7-nachr agonists

Abstract

The present invention relates to 1-aza-bicycloalkyl derivatives of formula I, wherein X is CH 2 or a single bond; Y is a group of formula and wherein R has the meanings as defined in the specification, which compounds are alpha 7 nicotinic acetylcholine receptor (nAChR) agonists; to processes for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them.

1 . A method for the prevention or treatment of a disease or disorder in a subject in need of such treatment, the method comprising:
 administering to the subject a therapeutically effective amount of a selective α7 nicotinic acetylcholine receptor (nAChR) agonist,   wherein the selective α7 nAChR agonist is (R)-3-(6-p-tolyl-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in free base form or in acid addition salt form.   
     
     
         2 . The method of  claim 1 , wherein the disease or disorder is a psychotic disorder. 
     
     
         3 . The method of  claim 2 , wherein the psychotic disorder is selected from the group consisting of: mania, depression, and anxiety. 
     
     
         4 . The method of  claim 1 , wherein the disease or disorder is a neurodegenerative disorder. 
     
     
         5 . The method of  claim 4 , wherein the neurodegenerative disorder is selected from the group consisting of: senile dementia, Alzheimer's disease, and an intellectual impairment disorder. 
     
     
         6 . The method of  claim 1 , wherein the disease or disorder is attention deficit hyperactivity disorder (ADHD), Parkinson's Disease, Huntington's chorea, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, convulsions, Tourette syndrome, obsessive compulsive disorder (OCD), memory deficits and dysfunction, a learning deficit, a panic disorder, narcolepsy, nociception, AIDS dementia, autism, tardive dyskinesia, social phobia, or pseudodementia. 
     
     
         7 . The method of  claim 1 , wherein the disease or disorder is neuropathic pain, postoperative pain, inflammatory pain, or phantom limb pain. 
     
     
         8 . A method for improving cognition in a subject in need of such treatment, the method comprising:
 administering to the subject a therapeutically effective amount of a selective α7 nicotinic acetylcholine receptor (nAChR) agonist, wherein the selective α7 nAChR agonist is (R)-3-(6-p-tolyl-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in free base form or in acid addition salt form.