Alkoxy pyrimidine PDE10 inhibitors

摘要

The present invention is directed to 2-alkoxy pyrimidine compounds which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

主权项

1. A compound of the formula I: wherein: R1 is C1-6alkyl or C1-6alkyl-C3-6cycloalkyl, which is unsubstituted or substituted with a substituent selected from the group consisting of:
(1) phenyl, which is unsubstituted or substituted with one to five substituents selected from R6, R7 and R8,(2) heteroaryl, which is unsubstituted or substituted with one to five substituents selected from R6, R7 and R8,(3) —O-phenyl, which is unsubstituted or substituted with one to five substituents selected from R6, R7 and R8, and(4) —O-heteroaryl, which is unsubstituted or substituted with one to five substituents selected from R6, R7 and R8; R2 is selected from the group consisting of:
(1) halogen,(2) hydroxyl,(3) C1-6alkyl,(4) —O—C1-6alkyl,(5) hydrogen,(6) —CN,(7) —S—C1-6alkyl,(8) —NR10R11, wherein R10 and R11 are independently selected from the group consisting of hydrogen and C1-6alkyl, and(9) heteroaryl, which is unsubstituted or substituted with one to five substituents selected from R6, R7 and R8, R3 is
C1-6alkyl, which is unsubstituted or substituted with halogen; R4 is selected from the group consisting of:
(1) hydrogen, and(2) C1-6alkyl; R5 is C1-6alkyl, C1-6alkyl-C3-6cycloalkyl or C2-6alkenyl which is unsubstituted or substituted with a substituent selected from the group consisting of:
(1) halogen,(2) hydroxyl,(3) —O—C1-6alkyl, which is unsubstituted or substituted with halogen or hydroxyl,(4) phenyl, which is unsubstituted or substituted with one to five substituents selected from R6, R7 and R8, and(5) heteroaryl, which is unsubstituted or substituted with one to five substituents selected from R6, R7 and R8; R6, R7 and R8 are independently selected from the group consisting of:
(1) halogen,(2) hydroxyl,(3) C1-6alkyl, which is unsubstituted or substituted with fluoro,(4) —O—C1-6alkyl, which is unsubstituted or substituted with fluoro,(5) —NR10R11,(6) —(C═O)—NR10R11,(7) —S(O)2—NR10R11,(8) —S(O)q—R12, where q is 0, 1 or 2 and where R12 is selected from the group consisting of hydrogen and C1-6alkyl, and(9) —CN; or a pharmaceutically acceptable salt thereof.