Pde-10 inhibitors

Abstract

Vicinal substituted cyclopropyl compounds which are inhibitors of phosphodiesterase 10 are described as are processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of mammals, including human(s) for central nervous system (CNS) disorders and other disorders which may affect CNS function, for example neurological, neurodegenerative and psychiatric disorders including, but not limited to, those comprising cognitive deficits or schizophrenic symptoms.

1 - 78 . (canceled) 
     
     
         79 . A pharmaceutical composition comprising:
 (a) a compound of Formula (I) or (II)   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein: 
         X is hydrogen, halogen, C 3 -C 8  alkyl, C 1 -C 4  alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkyloxy, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkoxy, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted heterocycloalkyloxy, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heteroaryloxy or optionally substituted heteroarylalkyl; 
         Y is hydrogen, C 3 -C 8  alkyl, C 1 -C 4  alkoxy, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted phenyl or optionally substituted heteroaryl; 
         T 1  is C; 
         T 2  is C; 
         Z 1  is CR 1  or N; 
         Z 2  is CR 2  or N; 
         Z 3  is CR 3  or N; 
         Z 4  is CR 4  or N; 
         HET is (i) an optionally substituted monocyclic heteroaryl having 5 ring atoms selected from the group consisting of C, O, S and N provided the total number of ring heteroatoms is less than or equal to three and wherein no more than one of the total number of heteroatoms is oxygen or sulfur, (ii) an optionally substituted monocyclic heteroaryl having 6 atoms selected from the group consisting of C and N provided that not more than 2 ring atoms are N, or (iii) an optionally substituted monocyclic heterocycloalkyl; 
         R 1  is hydrogen, halogen, C 1 -C 4  alkyl, optionally substituted C 3 -C 6  cycloalkyl, C 1 -C 4  alkoxy, optionally substituted C 3 -C 6  cycloalkyloxy, cyano, amino, alkylamino, dialkylamino, alkylsulfonyl, carboxy, nitro amido, alkylamido or dialkylamido; 
         R 2  is hydrogen, halogen, C 1 -C 4  alkyl, optionally substituted C 3 -C 6  cycloalkyl, C 1 -C 4  alkoxy, optionally substituted C 3 -C 6  cycloalkyloxy, cyano, amino, alkylamino, dialkylamino, alkylsulfonyl, carboxy, nitro amido, alkylamido or dialkylamido; 
         R 3  is hydrogen, halogen, C 1 -C 4  alkyl, optionally substituted C 3 -C 6  cycloalkyl, C 1 -C 4  alkoxy, optionally substituted C 3 -C 6  cycloalkyloxy, cyano, amino, alkylamino, dialkylamino, alkylsulfonyl, carboxy, nitro amido, alkylamido or dialkylamido; 
         R 4  is hydrogen, halogen, C 1 -C 4  alkyl, optionally substituted C 3 -C 6  cycloalkyl, C 1 -C 4  alkoxy, optionally substituted C 3 -C 6  cycloalkyloxy, cyano, amino, alkylamino, dialkylamino, alkylsulfonyl, carboxy, nitro amido, alkylamido or dialkylamido; 
         R 5  is hydrogen, halogen, C 1 -C 4  alkyl, optionally substituted C 3 -C 6  cycloalkyl, C 1 -C 4  alkoxy, optionally substituted C 3 -C 6  cycloalkyloxy, cyano, amino, alkylamino, dialkylamino, alkylsulfonyl, carboxy, nitro amido, alkylamido or dialkylamido; 
         R 6  is hydrogen, halogen, C 1 -C 4  alkyl, optionally substituted C 3 -C 6  cycloalkyl, C 1 -C 4  alkoxy, optionally substituted C 3 -C 6  cycloalkyloxy, cyano, amino, alkylamino, dialkylamino, alkylsulfonyl, carboxy, nitro amido, alkylamido or dialkylamido; 
         R 7  is hydrogen, C 1 -C 4  alkyl or optionally substituted C 3 -C 6  cycloalkyl; and 
         R 5  is hydrogen, C 1 -C 4  alkyl or optionally substituted C 3 -C 6  cycloalkyl; and 
         (b) and a pharmaceutically acceptable carrier or excipient. 
       
     
     
         80 . The pharmaceutical composition of  claim 79 , wherein R 7  is hydrogen or C 1 -C 4 . 
     
     
         81 . The pharmaceutical composition of  claim 79 , wherein R 8  is hydrogen or C 1 -C 4  alkyl. 
     
     
         82 . The pharmaceutical composition of  claim 79 , wherein R 5  is hydrogen, halogen, C 1 -C 4  alkyl, C 3 -C 6  cycloalykl, C 1 -C 4  alkoxy, C 3 -C 6  cycloalkyloxy, cyano or alkylsulfonyl. 
     
     
         83 . The pharmaceutical composition of  claim 79 , wherein R 6  is hydrogen, halogen, C 1 -C 4  alkyl, C 3 -C 6  cycloalykl, C 1 -C 4  alkoxy, C 3 -C 6  cycloalkyloxy, cyano or alkylsulfonyl. 
     
     
         84 . The pharmaceutical composition of  claim 79 , wherein Y is C 3 -C 6  cycloalykl, C 4 -C 7  cycloalkylalkyl, C 4 -C 7  cycloalkylalkoxy, heterocycloalkyl, or heterocycloalkyloxy. 
     
     
         85 . The pharmaceutical composition of  claim 79 , wherein X is alkyl, phenyl or heteroaryl. 
     
     
         86 . The pharmaceutical composition of  claim 79 , wherein HET is a monocyclic heterocycloalkyl. 
     
     
         87 . The pharmaceutical composition of  claim 86 , wherein HET is a monocyclic heterocycloalkyl having only 6 ring atoms. 
     
     
         88 . The pharmaceutical composition of  claim 86 , wherein HET is a monocyclic heterocycloalkyl having only 5 ring atoms. 
     
     
         89 . The pharmaceutical composition of  claim 79 , wherein HET is imidazolyl, thiazolyl, oxazolyl, pyridinyl, pyrmidinyl, pyrazinyl, triazolyl, pyrazolyl, cinnolinyl, piperidinyl, pyrrolidinyl, tetrahydrofuranyl, or pyranyl.