Peripherally-acting cannabinoid receptor agonists for chronic pain

Patent metadata

Field	Value
Publication number	US-9656981-B2
Application number	US-201314416026-A
Country	US
Kind code	B2
Filing date	Jul 19, 2013
Priority date	Jul 20, 2012
Publication date	May 23, 2017
Grant date	May 23, 2017

Abstract

Peripherally acting cannabinoid agonist compounds, pharmaceutical compositions, and methods of using them are presented.

First claim

The invention claimed is:

1. A compound having the structure

wherein
Ar 1 is alkyl substituted 1-naphthyl;
m 1 is 1, 2, 3, 4, 5, or 6;
R 1 is morpholin-4-yl; and
G 1 is one, two, three, or four substituents, each independently selected from hydrogen, halogen, fluorine, hydroxyl, alkoxy, and methylenedioxy; and
each R 8 independently is H or alkyl.

2. The compound of claim 1 , wherein m 1 is 1 or 2.

3. The compound of claim 1 , wherein G 1 is one fluorine substituent.

4. The compound of claim 1 , wherein Ar 1 is selected from the group consisting of

and R 6 is alkyl.

5. The compound of claim 1 , wherein R 8 is hydrogen.

6. The compound of claim 1 , selected from:

7. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient.

8. A method for treating a disease or disorder in a subject comprising administering to a subject a compound according to claim 1 , wherein the disease or disorder may be treated by activating or blocking a peripheral cannabinoid receptor.

9. The method of claim 8 , wherein the compound has less than 10% permeability across the blood brain barrier, as measured using the Madin-Darby canine kidney cell line assay.

10. The method of claim 8 , wherein the disorder is pain.

11. The method of claim 10 , wherein the pain is chronic, inflammatory, or neuropathic.

12. The method of claim 8 , wherein said disease or disorder is hyperalgesia or allodynia.

13. The method of claim 8 , wherein said disease or disorder is rheumatoid arthritis, inflammatory bowel disorders, soft tissue pain, bone cancer pain, chemotherapy-induced neuropathy, pain caused by thermal injury, pain caused by nerve injury, and pain caused by cancer.

14. The method of claim 8 , wherein said disease or disorder is intraocular pressure.

15. The method of claim 8 , wherein said treatment is anti-emetic, or anti-nausea treatment.

16. The method of claim 8 , wherein said disease or disorder is a tumor.

17. The method of claim 8 , wherein said disease or disorder is a bone disease associated with accelerated bone resorption.

18. The method of claim 17 , wherein the bone disorder is osteoporosis, rheumatoid arthritis, or bone metastasis.

Assignees

• Univ California

Inventors

• Spigelman Igor
• Seltzman Herbert H
• Shiner Craig

Classifications

• C07D333/20 Primary

  by nitrogen atoms (nitro, nitroso radicals C07D333/12) · CPC title

• C07D307/52 Primary

  Radicals substituted by nitrogen atoms not forming part of a nitro radical · CPC title

• C07D209/14

  Radicals substituted by nitrogen atoms, not forming part of a nitro radical · CPC title

• C07C49/84

  containing ether groups, [IMAGE cpc-sch-C07C-0958.gif] groups,[IMAGE cpc-sch-C07C-0959.gif] groups, or[IMAGE cpc-sch-C07C-0960.gif] groups · CPC title

• C07C49/788

  with keto groups bound to a condensed ring system · CPC title