NOVEL COMPOUNDS AS OPIOID RECEPTOR MODULATORS

• US 20140256779A1
• Filed: 05/20/2014
• Published: 09/11/2014
• Est. Priority Date: 03/15/2004
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceuticals, Inc. (Johnson & Johnson)
• Inventors: Breslin, Henry J., Cai, Chaozhong, He, Wei, Kavash, Robert W.
• Granted Patent: US 9,205,076 B2
• Time in Patent Office: Days
• US Class Current: 514/400
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/4174 Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2806 Coating materials
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07D 233/64 with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
• CPC Class Codes: C07D 275/06 with hetero atoms directly attached to the ring sulfur atom

Abstract

The present invention is directed to novel opioid receptor modulators of Formula (I).

The invention further relates to methods for preparing such compounds, pharmaceutical compositions containing them, and their use in the treatment of disorders that may be ameliorated or treated by the modulation of opioid receptors.

Claims

1. A method for treating pain or gastrointestinal disorder, wherein said pain is centrally mediated pain, peripherally mediated pain, structural or soft tissue injury related pain, pain related to inflammation, progressive disease related pain, neuropathic pain, acute pain, or chronic pain, and wherein said gastrointestinal disorder is ulcerative colitis, Crohn'"'"'s disease, diarrhea-predominant irritable bowel syndrome, or alternating irritable bowel syndrome, in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound having the structure:

2. The method according to claim 1, wherein said compound has the structure:

3. The method according to claim 2, wherein said compound has the structure:

4. The method according to claim 2, wherein said compound has the structure:

5. The method according to claim 2, wherein said compound has the structure:

6. The method according to claim 1, comprising administering to the subject a therapeutically effective amount of a pharmaceutically acceptable salt of said compound.

7. The method according to claim 6, wherein the salt is a hydrochloric, hydrobromic, hydriodic, perchloric, sulfuric, nitric, phosphoric, acetic, propionic, glycolic, lactic, succinic, maleic, fumaric, malic, tartaric, citric, benzoic, mandelic, methanesulfonic, hydroxyethanesulfonic, benzenesulfonic, oxalic, pamoic, 2-naphthalenesulfonic, p-toluenesulfonic, cyclohexanesulfamic, salicylic, saccharinic, or trifluoroacetic acid salt.

8. The method according to claim 6, wherein the salt is a benzathine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine, procaine, aluminum, calcium, lithium, magnesium, potassium, sodium, or zinc salt.

9. The method according to claim 1, wherein the chronic pain is selected from the group consisting of neuropathic pain conditions, diabetic peripheral neuropathy, post-herpetic neuralgia, trigeminal neuralgia, post-stroke pain syndromes and cluster or migraine headaches.

10. The method of claim 1, wherein the method is for treating centrally mediated pain.

11. The method according to claim 1, wherein the method is for treating peripherally mediated pain.

12. The method according to claim 1, wherein the method is for treating structural or soft tissue injury related pain.

13. The method according to claim 1, wherein the method is for treating pain related to inflammation.

14. The method according to claim 1, wherein the method is for treating progressive disease related pain.

15. The method according to claim 1, wherein the method is for treating neuropathic pain.

16. The method according to claim 1, wherein the method is for treating acute pain.

17. The method according to claim 1, wherein the method is for treating chronic pain.

18. The method according to claim 17, wherein the chronic pain is selected from the group consisting of neuropathic pain conditions, diabetic peripheral neuropathy, post-herpetic neuralgia, trigeminal neuralgia, post-stroke pain syndromes and cluster or migraine headaches.

19. The method according to claim 1, wherein the method is for treating ulcerative colitis.

20. The method according to claim 1, wherein the method is for treating Crohn'"'"'s disease.

21. The method according to claim 1, wherein the method is for treating diarrhea-predominant irritable bowel syndrome.

22. The method according to claim 1, wherein the method is for treating alternating irritable bowel syndrome.

23. A method for treating diarrhea-predominant irritable bowel syndrome in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound having the structure: