Inhibiting the transient receptor potential A1 ion channel

Patent metadata

Field	Value
Publication number	US-10519158-B2
Application number	US-201816234809-A
Country	US
Kind code	B2
Filing date	Dec 28, 2018
Priority date	Sep 19, 2014
Publication date	Dec 31, 2019
Grant date	Dec 31, 2019

Abstract

The present invention relates to pharmaceutical compounds of the Formula (I), or a pharmaceutically acceptable salt or composition thereof, and methods of their use for the treatment of pain, respiratory conditions, as well as inhibiting the Transient Receptor Potential A1 ion channel (TRPA1).

First claim

The invention claimed is:

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is

R 2 is is methyl;
R 3 is

R 4 is independently H, methyl, ethyl, propyl, cyano, methoxy, chlorine, fluorine, bromine, —CF 3 , —CF 2 ,

R 5 is independently H, —CF 3 , cyanomethyl, bromine, chlorine, fluorine, methyl, ethyl, isopropyl, cyano, keto,

R 6 is H; and

R 8 is H, methyl, ethyl, or CF 3 .

2. The compound of claim 1 , wherein R 1 is

3. The compound of claim 1 wherein R 1 is

4. The compound of claim 2 wherein R 3 is

5. The compound of claim 2 wherein R 3 is

6. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 6 which is:

8. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 8 which is:

10. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 10 which is:

12. A pharmaceutical composition comprising a compound according to claim 6 or a pharmaceutically acceptable salt thereof in a mixture with a pharmaceutically acceptable excipient, diluent, or carrier.

13. A pharmaceutical composition comprising a compound according to claim 8 or a pharmaceutically acceptable salt thereof in a mixture with a pharmaceutically acceptable excipient, diluent, or carrier.

14. A pharmaceutical composition comprising a compound according to claim 10 or a pharmaceutically acceptable salt thereof in a mixture with a pharmaceutically acceptable excipient, diluent, or carrier.

15. A method of treating chronic pain in a subject comprising administering an effective amount of a compound according to claim 6 , or a pharmaceutically acceptable salt thereof.

16. A method of treating chronic pain in a subject comprising administering an effective amount of a compound according to claim 8 , or a pharmaceutically acceptable salt thereof.

17. A method of treating chronic pain in a subject comprising administering an effective amount of a compound according to claim 10 , or a pharmaceutically acceptable salt thereof.

18. A method of treating neuropathic pain in a subject comprising administering an effective amount of a compound according to claim 6 , or a pharmaceutically acceptable salt thereof.

19. A method of treating neuropathic pain in a subject comprising administering an effective amount of a compound according to claim 8 , or a pharmaceutically acceptable salt thereof.

20. A method of treating neuropathic pain in a subject comprising administering an effective amount of a compound according to claim 10 , or a pharmaceutically acceptable salt thereof.

Assignees

• Lilly Co Eli

Inventors

• Chenard Bertrand L
• Wu Xinyuan

Classifications

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title

• A61K31/52

  Purines, e.g. adenine · CPC title

• C07K14/705

  Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} · CPC title

• C07D473/08 Primary

  with methyl radicals in positions 1 and 3, e.g. theophylline · CPC title