Compounds as opioid receptor modulators
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.
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:
or a pharmaceutically acceptable salt thereof.
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:
or a pharmaceutically acceptable salt thereof.