3,3-difluoropiperidine carbamate heterocyclic compounds as NR2B NMDA receptor antagonists
Disclosed are chemical entities of Formula (I): wherein R 1 and Z are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of Formula (I), and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of Formula (I).
1. A chemical entity, which is a compound of formula:
wherein:
R 5 is selected from the group consisting of —H, —CH 3 , —F, —Cl, —CH 2 CH 3 , —CF 2 H, —CH 2 F, —CF 3 , —CF 2 CH 3 , —CH 2 CF 3 , cyclopropyl, —OCF 3 , —OCF 2 H, —SCH 3 , —SO 2 CH 3 , and ethynyl;
R 6 is selected from the group consisting of —H and —F;
R 7 is selected from the group consisting of —H, —F, —Cl, and —CH 3 ; and
Z is
2. A pharmaceutical composition comprising the chemical entity of claim 1 and a pharmaceutically acceptable carrier.
3. The pharmaceutical composition of claim 2 , which is suitable for oral administration.
4. The chemical entity of claim 1 , wherein R 5 is —H, R 6 is —H, and R 7 is —H.
5. The chemical entity of claim 1 , wherein R 5 is —CH 3 , R 6 is —H, and R 7 is —H.
6. The chemical entity of claim 1 , wherein R 5 is —Cl, R 6 is —H, and R 7 is —H.
7. The chemical entity of claim 1 , wherein R 5 is —F, R 6 is —H, and R 7 is —H.
8. The chemical entity of claim 1 , wherein R 5 is —CH 2 CH 3 , R 6 is —H, and R 7 is —H.
9. The chemical entity of claim 1 , wherein R 5 is —CF 2 H, R 6 is —H, and R 7 is —H.
10. The chemical entity of claim 1 , wherein R 5 is —CH 2 F, R 6 is —H, and R 7 is —H.
11. The chemical entity of claim 1 , wherein R 5 is —CF 3 , R 6 is —H, and R 7 is —H.
12. The chemical entity of claim 1 , wherein R 5 is —CF 2 CH 3 , R 6 is —H, and R 7 is —H.
13. The chemical entity of claim 1 , wherein R 5 is —CH 2 CF 3 , R 6 is —H, and R 7 is —H.
14. The chemical entity of claim 1 , wherein R 5 is cyclopropyl, R 6 is —H, and R 7 is —H.
15. The chemical entity of claim 1 , wherein R 5 is —OCF 3 , R 6 is —H, and R 7 is —H.
16. The chemical entity of claim 1 , wherein R 5 is —OCF 2 H, R 6 is —H, and R 7 is —H.
17. The chemical entity of claim 1 , wherein R 5 is —Cl, R 6 is —H, and R 7 is —F.
18. The chemical entity of claim 1 , wherein R 5 is —CH 3 , R 6 is —H, and R 7 is —F.
19. The chemical entity of claim 1 , wherein R 5 is —CH 3 , R 6 is —F, and R 7 is —H.
20. The chemical entity of claim 1 , wherein R 5 is —Cl, R 6 is —F, and R 7 is —H.
21. The chemical entity of claim 1 , wherein R 5 is —F, R 6 is —F, and R 7 is —H.
22. The chemical entity of claim 1 , wherein R 5 is —F, R 6 is —H, and R 7 is —F.
23. The chemical entity of claim 1 , wherein R 5 is —F, R 6 is —H, and R 7 is —Cl.
24. The chemical entity of claim 1 , wherein R 5 is —F, R 6 is —H, and R 7 is —CH 3 .
25. The chemical entity of claim 1 , wherein R 5 is —Cl, R 6 is —H, and R 7 is —CH 3 .
26. The chemical entity of claim 1 , wherein R 5 is —SCH 3 , R 6 is —H, and R 7 is —H.
27. The chemical entity of claim 1 , wherein R 5 is —SO 2 CH 3 , R 6 is —H, and R 7 is —H.
28. The chemical entity of claim 1 , wherein R 5 is ethynyl, R 6 is —H, and R 7 is —H.