Additional heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists

Abstract

The present invention relates to new compounds of formula I, to pharmaceutical formulations containing the compounds, and to the use of the compounds in the prevention and/or treatment of mGluR5 receptor-mediated disorders.

1 . A compound selected from the group consisting of the compounds set forth in the following table:  
       
         
           
                 
                 
               
                     
                 
                     
                 
                     
                     
                 
                   943 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   944 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   945 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   946 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   947 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   949 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   951 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   952 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   955 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   959 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   967 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                     
                 
             
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         2 - 11 . (canceled)  
     
     
         12 . A method of prevention and/or treatment of mGluR5 receptor-mediated disorders, comprising administering to a mammal in need of such prevention and/or treatment a therapeutically effective amount of a compound according to  claim 1 .  
     
     
         13 . The method according to  claim 12 , wherein the disorder is a neurological disorder.  
     
     
         14 . The method according to  claim 12 , wherein the disorder is a psychiatric disorder.  
     
     
         15 . The method according to  claim 12 , wherein the disorder is selected from chronic and acute pain disorders.  
     
     
         16 . The method according to  claim 12 , wherein the disorder is a gastrointestinal disorder.  
     
     
         17 . The method according to  claim 12 , wherein the disorder is selected from the group consisting of Alzheimer's disease, senile dementia, AIDS-induced dementia, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's Chorea, migraine, epilepsy, schizophrenia, depression, anxiety, acute anxiety, obsessive compulsive disorder, opthalmological disorders, diabetic retinopathies, glaucoma, auditory neuropathic disorders, chemotherapy induced neuropathies, post-herpetic neuralgia and trigeminal neuralgia, tolerance, dependency, addiction and craving disorders, neurodevelopmental disorders, autism, mental retardation, schizophrenia, Down's Syndrome, pain related to migraine, inflammatory pain, neuropathic pain disorders, arthritis and rheumatoid diseases, low back pain, post-operative pain, pain associated with angina, renal and biliary colic, menstruation, migraine gout, stroke, head trauma, anoxic and ischemic injuries, hypoglycemia, cardiovascular diseases and epilepsy.  
     
     
         18 . A method for inhibiting the activation of mGluR5 receptors, comprising treating a cell containing said receptor with an effective amount of a compound according to  claim 1 .  
     
     
         19 . A pharmaceutical formulation comprising as active ingredient a therapeutically effective amount of the compound according to  claim 1  in association with one or more pharmaceutically acceptable diluents, excipients and/or inert carriers.