Chromane, isochromane and dihydroisobenzofuran derivatives as mGluR2—negative allosteric modulators, compositions, and their use
View Patent ↗The present invention provides certain substituted chromane, isochromane, and dihydroisobenzofuran compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein ring A is a moiety selected from: and ring B, n, R 1 , R 2 , R 2A , R 3 , and R 3A are as defined herein. The compounds of the invention are useful as mGluR2 inhibitors, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a patient for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, mild cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.
1. A compound having the structure:
2. A compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt.
3. A compound having the structure:
4. A compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt.
5. A compound having the structure:
6. A compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt.
7. A compound having the structure:
8. A compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt.
9. A compound having the structure:
10. A compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt.
11. A compound having the structure:
12. A compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt.
13. A compound having the structure:
14. A compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt.
15. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt, according to claim 2 .
17. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 3 and a pharmaceutically acceptable carrier.
18. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt, according to claim 4 .
19. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 5 and a pharmaceutically acceptable carrier.
20. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt, according to claim 6 .
21. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 7 and a pharmaceutically acceptable carrier.
22. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt, according to claim 8 .
23. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 9 and a pharmaceutically acceptable carrier.
24. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt, according to claim 10 .
25. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 11 and a pharmaceutically acceptable carrier.
26. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt, according to claim 12 .
27. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 13 and a pharmaceutically acceptable carrier.
28. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound having the structure:
wherein said compound is in the form of a pharmaceutically acceptable salt, according to claim 14 .