Chromane, isochromane and dihydroisobenzofuran derivatives as mGluR2—negative allosteric modulators, compositions, and their use

Patent metadata

Field	Value
Publication number	US-10335399-B2
Application number	US-201715713769-A
Country	US
Kind code	B2
Filing date	Sep 25, 2017
Priority date	Sep 27, 2016
Publication date	Jul 2, 2019
Grant date	Jul 2, 2019

Abstract

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.

First claim

What is claimed is:

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 .

Assignees

• Merck Sharp & Dohme

Inventors

• Sebhat Iyassu K
• Arasappan Ashok
• Hoyt Scott B
• Wilkening Robert R
• Demong Duane

Classifications

• A61P25/28

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• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title