Agonists of the mu opioid receptor
The present technology is directed to compounds, compositions, and methods related to non-morphinan-like mu opioid receptor agonists. Compounds of the present technology demonstrate remarkable potency and selectivity for the mu opioid receptor over the kappa opioid receptor, while also exhibiting a significant reduction (or, essentially, absence) of the negative side effects of many morphine-derived compounds.
1. A compound of Formula I:
or a pharmaceutically acceptable salt and/or solvate thereof, wherein
R 1 is
—CH 2 Ph, —CH 2 CH 2 Ph, —CH═CH-Ph, or heteroaryl; and
R 2 , R 3 , and R 4 are each independently H, halo, OH, nitro, unsubstituted C 1 -C 3 alkyl, or unsubstituted C 1 -C 3 alkoxy.
2. The compound of claim 1 , wherein R 1 is
—CH═CH-Ph, or heteroaryl.
3. The compound of claim 1 , wherein R 2 , R 3 , and R 4 are each independently H, halo, OH, nitro, unsubstituted C 1 -C 3 n-alkyl, or unsubstituted C 1 -C 3 n-alkoxy.
4. The compound of claim 1 , wherein R 2 is H, halo, or unsubstituted C 1 -C 3 alkyl.
5. The compound of claim 1 , wherein heteroaryl is furanyl, thiophenyl, pyridinyl, pyrimidinyl, 4-thiazolyl, or 4-oxazolyl.
6. The compound of claim 1 , wherein heteroaryl is furanyl, thiophenyl, pyrimidinyl, 4-thiazolyl, 4-oxazolyl, 4-pyridinyl, or
wherein one of X 1 and X 2 is N and the remaining X 1 or X 2 is CH; and R 6 is H, OH, or C 1 -C 3 alkoxy.
7. The compound of claim 1 , wherein heteroaryl is unsubstituted 2-furanyl, unsubstituted 2-benzofuranyl, unsubstituted 3-furanyl, unsubstituted 2-thiophenyl, unsubstituted 3-thiophenyl, unsubstituted 5-pyrimidinyl, unsubstituted 4-thiazolyl, unsubstituted 4-oxazolyl, unsubstituted 4-pyridinyl, or
wherein one of X 1 and X 2 is N and the remaining X 1 or X 2 is CH; and R 6 is H, OH, or C 1 -C 3 alkoxy.
8. The compound of claim 1 , wherein
R 1 is
—CH 2 Ph, —CH 2 CH 2 Ph, —CH═CH-Ph, furanyl, thiophenyl, pyrimidinyl, 4-thiazolyl, 4-oxazolyl, 4-pyridinyl, or
wherein one of X 1 and X 2 is N and the remaining X 1 or X 2 is CH; and R 6 is H, OH, or C 1 -C 3 alkoxy; and
R 2 , R 3 , and R 4 are each independently H, halo, OH, nitro, unsubstituted C 1 -C 3 n-alkyl, or unsubstituted C 1 -C 3 n-alkoxy.
9. The compound of claim 1 , wherein
R 1 is
—CH 2 Ph, —CH 2 CH 2 Ph, —CH═CH-Ph, unsubstituted 2-furanyl, unsubstituted 2-benzofuranyl, unsubstituted 3-furanyl, unsubstituted 2-thiophenyl, unsubstituted 3-thiophenyl, unsubstituted 5-pyrimidinyl, unsubstituted 4-thiazolyl, unsubstituted 4-oxazolyl, unsubstituted 4-pyridinyl, or
wherein one of X 1 and X 2 is N and the remaining X 1 or X 2 is CH; and R 6 is H, OH, or C 1 -C 3 alkoxy; and
R 2 , R 3 , and R 4 are each independently H, halo, OH, nitro, unsubstituted C 1 -C 3 n-alkyl, or unsubstituted C 1 -C 3 n-alkoxy.
10. The compound of claim 1 , wherein
R 1 is
—CH═CH-Ph, unsubstituted 2-furanyl, unsubstituted 2-benzofuranyl, unsubstituted 3-furanyl, unsubstituted 2-thiophenyl, unsubstituted 3-thiophenyl, unsubstituted 5-pyrimidinyl, unsubstituted 4-thiazolyl, unsubstituted 4-oxazolyl, unsubstituted 4-pyridinyl, or
wherein one of X 1 and X 2 is N and the remaining X 1 or X 2 is CH; and R 6 is H, OH, or C 1 -C 3 alkoxy; and
R 2 , R 3 , and R 4 are each independently H, halo, OH, nitro, unsubstituted C 1 -C 3 n-alkyl, or unsubstituted C 1 -C 3 n-alkoxy.
11. The compound of claim 1 , wherein the compound is
12. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
13. A composition comprising the compound of claim 8 and a pharmaceutically acceptable carrier.
14. A composition comprising the compound of claim 10 and a pharmaceutically acceptable carrier.
15. A pharmaceutical composition comprising an effective amount of the compound of claim 1 for treating pain in a subject, and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition comprising an effective amount of the compound of claim 8 for treating pain in a subject, and a pharmaceutically acceptable carrier.
17. A method comprising administering an effective amount of a compound of claim 1 to a subject in need thereof.
18. The method of claim 17 , wherein the subject is suffering from at least one of acute pain and chronic pain.
19. A method of binding the mu opioid receptor, the method comprising contacting a mu opioid receptor with a compound of claim 1 .
20. The method of claim 19 , wherein the contacting comprises a cell not within a patient.