Oligomer-opioid agonist conjugates
View Patent ↗The invention provides compounds that are chemically modified by covalent attachment of a water-soluble oligomer. A compound of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from those of the compound not attached to the water-soluble oligomer.
1. A compound selected from a compound of Formula II-Cb
wherein:
N* is nitrogen;
Ar is selected from the group consisting of cyclohexyl, phenyl, halophenyl, methoxyphenyl, aminophenyl, pyridyl, furyl and thienyl;
Alk is selected from the group consisting of ethylene and propylene;
R II is selected from the group consisting of lower alkyl, lower alkoxy, dimethylamino, cyclopropyl, 1-pynolidyl, morpholino;
R II ′ is selected from the group consisting of hydrogen, methyl and methoxy;
R II ″ is selected from the group consisting of hydrogen and lower alkyl;
X is a covalent bond or O; and
POLY is a poly(alkylene oxide) oligomer;
and pharmaceutically acceptable salts thereof.
2. The compound of claim 1 , wherein Alk is ethylene.
3. The compound of claim 2 , wherein R II is lower alkyl.
4. The compound of claim 2 , wherein R II is ethyl.
5. The compound of claim 3 , wherein R II ′ is hydrogen.
6. The compound of claim 5 , wherein R II ″ is hydrogen.
7. The compound of claim 6 , wherein Ar is phenyl.
8. The compound of claim 7 , wherein the poly(alkylene oxide) is poly(ethylene oxide).
9. The compound of claim 8 , wherein the poly(ethylene oxide) includes an alkoxy or hydroxyl end-capping moiety.
10. The compound of claim 9 , wherein the poly(ethylene oxide) is made of between 2 and 30 monomers.
11. The compound of claim 10 , wherein the poly(ethylene oxide) is made of between 2 and 10 monomers.
12. A compound selected from a compound of the formula
wherein n is an integer from 1 to 30; and pharmaceutically acceptable salts thereof.
13. The compound of claim 12 , wherein n is an integer from 1 to 10.
14. A compound selected from a compound of the formula
wherein n is an integer from 1 to 30; and pharmaceutically acceptable salts thereof.
15. The compound of claim 14 , wherein n is an integer from 1 to 10.
16. A composition comprising a compound of claim 1 , and optionally, a pharmaceutically acceptable excipient.
17. The composition of claim 16 , wherein the composition is suitable for oral administration.
18. A composition of matter comprising a compound of claim 1 , wherein the compound is present in a dosage form.
19. A method of treating pain in a patient, comprising administering a therapeutically effective amount of a compound of claim 1 to the patient in need thereof.
20. A method of treating pain in a patient, comprising administering the composition of claim 16 to the patient in need thereof.
21. A composition comprising a compound of claim 12 , and optionally, a pharmaceutically acceptable excipient.
22. The composition of claim 21 , wherein the composition is suitable for oral administration.
23. A composition of matter comprising a compound of claim 12 , wherein the compound is present in a dosage form.
24. A method of treating pain in a patient, comprising administering a therapeutically effective amount of a compound of claim 12 to the patient in need thereof.
25. A method of treating pain in a patient, comprising administering the composition of claim 21 to the patient in need thereof.
26. A composition comprising a compound of claim 14 , and optionally, a pharmaceutically acceptable excipient.
27. The composition of claim 26 , wherein the composition is suitable for oral administration.
28. A composition of matter comprising a compound of claim 14 , wherein the compound is present in a dosage form.
29. A method of treating pain in a patient, comprising administering a therapeutically effective amount of a compound of claim 14 to the patient in need thereof.
30. A method of treating pain in a patient, comprising administering the composition of claim 26 to the patient in need thereof.