Pyrimidine PDE10 inhibitors
View Patent ↗The present invention is directed to 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.
1. A compound selected from the group consisting of
2-Methyl-6-{2-(5-methylpyridin-2-yl)cyclopropyl]methoxy}-N-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]pyrimidin-4-amine,
2-Methyl-6-{[(1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl]methoxy}-N-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]pyrimidin-4-amine,
S,S-2-methyl-N-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]-6-{[2-(1,5-naphthyridin-2-yl)cyclopropyl]methoxy}pyrimidin-4-amine,
6-{[(1S,2 S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-N-4-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]pyrimidine-2,4-diamine,
5-fluoro-6-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-N-4-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]pyrimidine-2,4-diamine,
6-{[2-(3,3′-bipyridin-6-yl)cyclopropyl]methoxy}-2-methyl-N-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]pyrimidin-4-amine,
6-{[2-(5-cyclopropylpyridin-2-yl)cyclopropyl]methoxy}-2-methyl-N-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]pyrimidin-4-amine, and
2-amino-4-{[(1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl]methoxy}-6-{[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]amino}pyrimidine-5-carbonitrile, or a pharmaceutically acceptable salt thereof.
2. A compound of structural formula:
or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 2 which is.
4. The compound according to claim 2 which is
in the form of a pharmaceutically acceptable salt.
5. A compound which is
or a pharmaceutically acceptable salt thereof.
6. The compound according to claim 5 which is
7. The compound according to claim 5 which is
in the form of a pharmaceutically acceptable salt.
8. A compound which is
or a pharmaceutically acceptable salt thereof.
9. The compound according to claim 8 which is
10. The compound according to claim 8 which is
in the form of a pharmaceutically acceptable salt.
11. A compound which is
or a pharmaceutically acceptable salt thereof.
12. The compound according to claim 11 which is
13. The compound according to claim 11 which is
in the form of a pharmaceutically acceptable salt.
14. A compound which is
or a pharmaceutically acceptable salt thereof.
15. The compound according to claim 14 which is
16. The compound according to claim 14 which is
in the form of a pharmaceutically acceptable salt.
17. A compound which is
or a pharmaceutically acceptable salt thereof.
18. The compound according to claim 17 which is
19. The compound according to claim 17 which is
in the form of a pharmaceutically acceptable salt.
20. A compound which is
or a pharmaceutically acceptable salt thereof.
21. The compound according to claim 20 which is
22. The compound according to claim 20 which is
in the form of a pharmaceutically acceptable salt.
23. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.
24. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound of claim 3 .
25. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound according to claim 4 .
26. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound of claim 6 .
27. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound according to claim 7 .
28. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound of claim 9 .
29. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound according to claim 10 .
30. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound of claim 12 .
31. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound according to claim 13 .
32. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound of claim 15 .
33. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound according to claim 16 .
34. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound of claim 18 .
35. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound according to claim 19 .
36. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound of 21.
37. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and the compound according to claim 22 .