Opioid and opioid-like compounds and uses thereof
The present invention relates to opioid and opioid-like compounds, and pharmaceutical formulations containing the same and methods of use thereof. Uses of the present invention include, but are not limited to, use for the prevention and treatment of septic shock and other disorders. The compounds described herein can be water soluble and can act through mechanisms mediated through pathways other than opiate receptors.
1. A compound according to the formula R-A-X:
wherein,
R is attached to the 3-position of the morphinan ring and is lower alkyl, phenyl, pyridine;
A is a structure selected from the group consisting of the following structures:
X is attached to the nitrogen atom and is selected from the group consisting of (CH 2 )C 6 H 5 -4F, phenyl or substituted phenyl wherein the substituent is selected from the group consisting of lower alkyl, NO 2 , CF 3 , or OCH 3 ;
or enantiomers, diastereoisomers, or pharmaceutically acceptable salts thereof.
2. The compound of claim 1 , wherein X is selected from the group consisting of phenyl, 4-nitrophenyl, and (CH 2 )C 6 H 5 -4F.
3. A compound selected from the group consisting of 3-methoxy-17-(4-fluorobenzyl)morphinan, and 3-methoxy-17-(4-nitrophenyl)morphinan, 3-methoxy-17-(phenyl)morphinan, and enantiomers, diastereoisomers, and pharmaceutically acceptable salts thereof.
4. A pharmaceutical formulation comprising the compound of claim 1 and at least one pharmaceutically acceptable carrier, diluent, or excipient.
5. A pharmaceutical formulation comprising a compound of claim 1 , wherein the pharmaceutically acceptable carrier is an aqueous carrier.
6. A pharmaceutical formulation comprising the compound of claim 3 and at least one pharmaceutically acceptable carrier, diluent, or excipient.
7. A pharmaceutical formulation comprising a compound of claim 3 , wherein the pharmaceutically acceptable carrier is an aqueous carrier.
8. A method of treating rheumatoid arthritis, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of claim 1 .
9. A method of treating organ damage selected from liver, lung or kidney damage, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .
10. The method according to claim 9 , wherein the organ damage is liver damage.
11. The method according to claim 9 , wherein the organ damage is lung damage.
12. The method according to claim 9 , wherein the organ damage is kidney damage.
13. A method of treating diseases associated with overproduction of TNF α selected from the group consisting of arthritis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, multiple sclerosis, and pulmonary fibrosis, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .
14. A method of treating rheumatoid arthritis, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of claim 3 .
15. A method of treating organ damage selected from liver, lung or kidney damage, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 3 .
16. The method according to claim 15 , wherein the organ damage is liver damage.
17. The method according to claim 15 , wherein the organ damage is lung damage.
18. The method according to claim 15 , wherein the organ damage is kidney damage.
19. A method of treating diseases associated with overproduction of TNF α selected from the group consisting of arthritis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, multiple sclerosis, and pulmonary fibrosis, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 3 .
20. A method of treating conditions selected from the group consisting of, organ damage selected from liver, lung or kidney damage, rheumatoid arthritis, Crohn's disease, and multiple sclerosis, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of claim 1 in combination with a therapeutic agent selected from the group consisting of, antibiotics, and antivirals.
21. A method of treating conditions selected from the group consisting of organ damage selected from liver, lung or kidney damage, rheumatoid arthritis, Crohn's disease, and multiple sclerosis, comprising administering to a subject in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisting of 3 methoxy-17-benzylmorphinan and enantiomers, diastereoisomers, and pharmaceutically acceptable salts thereof.
22. The method of claims 21 , wherein the pharmaceutical composition is administered orally or parenterally.
23. The method of claim 22 wherein the pharmaceutical composition is administered in an amount selected from 2 to 100 mg per unit dose and one to four times a day.
24. The method according to claim 21 wherein the pharmaceutical composition is administered in combination with at least one other therapeutic agent selected from the group consisting of antibiotics, antimicrobials, antivirals, vaccines, and interferons.
25. A method of treating conditions selected from the group consisting of lung, liver or kidney damage, rheumatoid arthritis, Crohn's disease, and multiple sclerosis, comprising administering to a subject in need thereof, a pharmaceutical composition comprising administering to a subject in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of a compound according to the formula R-A-X:
wherein,
R is attached to the 3-position of the morphinan ring and is H, lower alkyl, phenyl, pyridine;
A is a structure selected from the group consisting of the following structures:
X is attached to the nitrogen atom and is selected from the group consisting of hydrogen, allyl, cinnamyl, crotonyl, (CH 2 )C 6 H 5 -4F, phenyl or substituted phenyl wherein said substituent is selected from the group consisting of NO 2 , CF 3 , or OCH 3 , or
enantiomers, diastereoisomers, or pharmaceutically acceptable salts thereof.
26. A method according to claim 13 wherein said compound is administered orally.
27. A method according to claim 13 wherein said compound is administered parenterally.
28. A method according to claim 15 wherein said compound is administered orally.
29. A method according to claim 15 wherein said compound is administered parenterally.
30. A method according to claim 19 wherein said compound is administered orally.
31. A method according to claim 19 wherein said compound is administered parenterally.
32. A method according to claim 25 wherein said compound is administered orally.
33. A method according to claim 25 wherein said compound is administered parenterally.