Pde10 inhibitors and related compositions and methods

Abstract

Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing a compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.

1 - 70 . (canceled) 
     
     
         71 . A compound having the following structure (III): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof,
 wherein: 
 R 1  is C 1-6 alkyl, C 1-6 haloalkyl, —(CH 2 ) n O(CH 2 ) m CH 3  or —(CH 2 ) n N(CH 3 ) 2 ; 
 R 2  and R 3  are the same or different and independently substituted or unsubstituted heterocyclyl, or substituted or unsubstituted aryl; and 
 R 4  and R 5  are the same or different and independently hydrogen, C 1-6 alkyl or C 1-6 haloalkyl; 
 n is 1, 2, 3, 4, 5 or 6; and 
 m is 0, 1, 2, 3, 4, 5 or 6. 
 
     
     
         72 . The compound of  claim 71  wherein R 4  and R 5  are the same or different and independently hydrogen or C 1-6 alkyl. 
     
     
         73 . The compound of  claim 71  wherein R 4  and R 5  are hydrogen. 
     
     
         74 . The compound of  claim 71  wherein R 1  is C 1-6 alkyl. 
     
     
         75 . The compound of  claim 74  wherein R 1  is methyl. 
     
     
         76 . The compound of  claim 74  wherein R 1  is ethyl. 
     
     
         77 . The compound of  claim 74  wherein R 1  is isopropyl. 
     
     
         78 . The compound of  claim 71  wherein R 3  is substituted phenyl. 
     
     
         79 . The compound of  claim 78  wherein R 3  is 3,4,5-trimethoxyphenyl. 
     
     
         80 . The compound of  claim 78  wherein R 3  is 4-bromo-3,5-dimethoxyphenyl. 
     
     
         81 . The compound of  claim 71  wherein R 2  is substituted or unsubstituted phenyl. 
     
     
         82 . The compound of  claim 81  wherein R 2  is 4-morpholinophenyl. 
     
     
         83 . The compound of  claim 81  wherein R 2  is 4-(1H-pyrazol-1-yl)phenyl. 
     
     
         84 . The compound of  claim 71  wherein R 2  is substituted or unsubstituted naphthyl. 
     
     
         85 . The compound of  claim 71  wherein R 2  is substituted or unsubstituted heteroaryl. 
     
     
         86 . A pharmaceutical composition comprising a compound of  claim 71  and a pharmaceutically acceptable carrier or diluent. 
     
     
         87 - 100 . (canceled)