5- and 6-membered heterocyclic compounds

Abstract

5- and 6-membered heterocyclic 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. Also described is the treatment of neurological, neurodegenerative and psychiatric disorders including but not limited to those comparing cognitive deficits or schizophrenic symptoms.

1 . A compound of Formula (I) or (II) or (III) or pharmaceutically acceptable salt thereof 
       
         
           
           
               
               
           
         
         Wherein: 
         HET is a heterocyclic ring selected from Formulas A1-A2, A6-A8, A10-A32 and A38 below 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and the left most radical is connected to the X group; 
         W is selected from halogen, cyano, nitro, alkoxy, amino, alkylamino, dialkylamino, carboxy, amido, alkylamido, and dialkylamido; 
         X is selected from C 3 -C 8  alkyl, optionally substituted C 3 -C 6  cycloalkyl, optionally substituted C 4 -C 7  cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl; 
         Y is a bond or a divalent linker group selected from —CH 2 —, —O—, —SO 2 —, —CH 2 O—, —OCH 2 — and —CH 2 CH 2 — with the rightmost radical of the Y group connected to the Z substituent; 
         Z is optionally substituted heteroaryl; 
         R 1a  is selected from hydrogen, C 1 -C 4  alkyl, optionally substituted C 3 -C 6  cycloalkyl, optionally substituted C 4 -C 7  cycloalkylalkyl and optionally substituted C 4 -C 7  alkoxyalkyl with the proviso that when R 1a  is not hydrogen, R 1b  is hydrogen or that when R 1b  is absent, R 1a  must be hydrogen; 
         R 1b  is selected from hydrogen, C 1 -C 4  alkyl, C 3 -C 6  optionally substituted cycloalkyl, optionally substituted C 4 -C 7  cycloalkylalkyl and optionally substituted C 4 -C 7  alkoxyalkyl with the proviso that when R 1b  is not hydrogen, R 1a  is hydrogen; 
         Each R 2  is independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl and optionally substituted alkoxyalkyl with the proviso that at least one R 2  is hydrogen; 
         R 3  and R 4  are independently selected from hydrogen, C 1 -C 4  alkyl, CF 3  and optionally substituted cycloalkyl with the proviso that at least one R 3  or R 4  group must be hydrogen; 
         R 5  is selected from alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl and optionally substituted alkoxyalkyl; 
         R 7  is selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl and optionally substituted alkoxyalkyl; and 
         n is independently selected from 1 and 2. 
       
     
     
         2 - 118 . (canceled)