Pyrimidine compounds and methods using the same

Abstract

The present invention relates to 2-amino-4-arylpyrimidine and 2-amino-4-aryltriazine compounds as inhibitors of heat shock protein 90 family of chaperone proteins. The invention also features pharmaceutical compositions and kits that include the compounds and compositions of the invention. The invention further relates to the medical use of these compounds and compositions for the treatment of a disorder hi a subject. For example, the disorder is a neurodegenerative disease.

1 - 17 . (canceled) 
     
     
         18 . A compound having the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         19 . A compound having the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         20 . A compound having the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         21 . A pharmaceutical composition comprising the compound of  claim 18 , or a pharmaceutically acceptable salt thereof, and one or more of pharmaceutically acceptable carriers or excipients. 
     
     
         22 - 23 . (canceled) 
     
     
         24 . A method of treating a disorder in a mammal caused by the action of heat shock protein 90 (Hsp90), said method comprising administering an effective amount of the compound of  claim 18  or a pharmaceutically acceptable salt thereof to said mammal. 
     
     
         25 - 26 . (canceled) 
     
     
         27 . The method of  claim 24 , wherein said disorder is a neurodegenerative disorder selected from Alzheimer's disease, Huntington's disease, progressive supranuclear palsy, Parkinson's disease, Pick's disease, corticobasal degeneration, chronic traumatic encephalopathy, traumatic brain injury, and frontotemporal dementia. 
     
     
         28 . The method of  claim 27 , wherein said neurodegenerative disorder is Alzheimer's disease. 
     
     
         29 - 43 . (canceled) 
     
     
         44 . A method of inhibiting Hsp90, said method comprising contacting a cell with the compound of  claim 18  or a pharmaceutically acceptable salt thereof. 
     
     
         45 . (canceled) 
     
     
         46 . A kit comprising:
 (i) the pharmaceutical composition of  claim 21 ; and   (ii) instructions for use of the pharmaceutical compositions of (i) to treat a disorder in a mammal caused by the action of Hsp90.   
     
     
         47 . A pharmaceutical composition comprising the compound of  claim 19 , or a pharmaceutically acceptable salt thereof, and one or more of pharmaceutically acceptable carriers or excipients. 
     
     
         48 . A method of treating a disorder in a mammal caused by the action of Hsp90, said method comprising administering an effective amount of the compound of  claim 19  or a pharmaceutically acceptable salt thereof to said mammal. 
     
     
         49 . The method of  claim 48 , wherein said disorder is a neurodegenerative disorder selected from Alzheimer's disease, Huntington's disease, progressive supranuclear palsy, Parkinson's disease, Pick's disease, corticobasal degeneration, chronic traumatic encephalopathy, traumatic brain injury, and frontotemporal dementia. 
     
     
         50 . The method of  claim 49 , wherein said neurodegenerative disorder is Alzheimer's disease. 
     
     
         51 . A method of inhibiting Hsp90, said method comprising contacting a cell with the compound of  claim 19  or a pharmaceutically acceptable salt thereof. 
     
     
         52 . A kit comprising:
 (i) the pharmaceutical composition of  claim 47 ; and   (ii) instructions for use of the pharmaceutical compositions of (i) to treat a disorder in a mammal caused by the action of Hsp90.   
     
     
         53 . A pharmaceutical composition comprising the compound of  claim 20 , or a pharmaceutically acceptable salt thereof, and one or more of pharmaceutically acceptable carriers or excipients. 
     
     
         54 . A method of treating a disorder in a mammal caused by the action of Hsp90, said method comprising administering an effective amount of the compound of  claim 20  or a pharmaceutically acceptable salt thereof to said mammal. 
     
     
         55 . The method of  claim 54 , wherein said disorder is a neurodegenerative disorder selected from Alzheimer's disease, Huntington's disease, progressive supranuclear palsy, Parkinson's disease, Pick's disease, corticobasal degeneration, chronic traumatic encephalopathy, traumatic brain injury, and frontotemporal dementia. 
     
     
         56 . The method of  claim 55 , wherein said neurodegenerative disorder is Alzheimer's disease. 
     
     
         57 . A method of inhibiting Hsp90, said method comprising contacting a cell with the compound of  claim 20  or a pharmaceutically acceptable salt thereof. 
     
     
         58 . A kit comprising:
 (i) the pharmaceutical composition of  claim 53 ; and   (ii) instructions for use of the pharmaceutical compositions of (i) to treat a disorder in a mammal caused by the action of Hsp90.