Inhibitors of beta-secretase

Abstract

The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the β-secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of β-amyloid aggregates.

1 - 13 . (canceled) 
     
     
         14 . A method of treating a BACE1 mediated disorder or disease in a subject, comprising administering to the subject an effective amount of a compound represented by a structural formula selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         15 . The method of  claim 14 , wherein the BACE1 mediated disorder or disease is selected from the group consisting of neurodegenerative disorder, cognitive decline, cognitive impairment, dementia and disease characterized by the production of β-amyloid deposits or neurofibrillary tangles. 
     
     
         16 . The method of  claim 15 , wherein the disorder or disease is selected from the group consisting of Alzheimer's disease, Trisomy 21 (Down Syndrome), Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-type (HCHWA-D), senile dementia, cerebral amyloid angiopathy, degenerative dementia, dementias of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer's disease, dry age related macular degeneration (AMD), and glaucoma. 
     
     
         17 - 18 . (canceled) 
     
     
         19 . A compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a salt thereof.