Quinoline carboxamide and quinoline carbonitrile derivatives as mGluR2-negative allosteric modulators, compositions, and their use

Patent metadata

Field	Value
Publication number	US-9278960-B2
Application number	US-201214356080-A
Country	US
Kind code	B2
Filing date	Oct 26, 2012
Priority date	Nov 3, 2011
Publication date	Mar 8, 2016
Grant date	Mar 8, 2016

Abstract

The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) wherein ring A, R Q , -L-, R 1 , n, R 2 , and R 3 are as defined herein. The compounds of the invention are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and in methods of treating a patient (preferably a human) for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, 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 selected from the group consisting of:

or a stereoisomer thereof, or a pharmaceutically acceptable salt of said compound or said stereoisomer.

2. A compound having a structure:

3. A pharmaceutical composition comprising the compound of claim 2 and a pharmaceutically acceptable carrier.

4. A compound having a structure:

in the form of a pharmaceutically acceptable salt.

5. A pharmaceutical composition comprising the compound of claim 4 in the form of a pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

6. A compound having a structure:

7. A pharmaceutical composition comprising the compound of claim 6 and a pharmaceutically acceptable carrier.

8. A compound having a structure:

in the form of a pharmaceutically acceptable salt.

9. A pharmaceutical composition comprising the compound of claim 8 in the form of a pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

10. A compound having a structure:

11. A pharmaceutical composition comprising the compound of claim 10 and a pharmaceutically acceptable carrier.

12. A compound having a structure:

in the form of a pharmaceutically acceptable salt.

13. A pharmaceutical composition comprising the compound of claim 12 in the form of a pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

14. A compound having a structure:

or a stereoisomer thereof.

15. A pharmaceutical composition comprising the compound of claim 14 or a stereoisomer thereof, and a pharmaceutically acceptable carrier.

16. A compound having a structure:

or a stereoisomer thereof, wherein said compound or said stereoisomer is in the form of a pharmaceutically acceptable salt.

17. A pharmaceutical composition comprising the compound of claim 16 or a stereoisomer thereof, wherein said compound or said stereoisomer is in the form of a pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier.

18. A compound having a structure:

19. A pharmaceutical composition comprising the compound of claim 18 and a pharmaceutically acceptable carrier.

20. A compound having a structure:

in the form of a pharmaceutically acceptable salt.

21. A pharmaceutical composition comprising the compound of claim 20 in the form of a pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

Assignees

• Merck Sharp & Dohme

Inventors

• Bungard Christopher James
• Converso Antonella
• Hanney Barbara
• Hartingh Timothy John
• Manley Peter J
• Meissner Robert S
• Perkins James J
• Rudd Michael T

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/18

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

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P25/20

  Hypnotics; Sedatives · CPC title