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 of Formula II-Cc
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-pyrrolidyl, 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;
each X is independently a covalent bond or O; and
each POLY is independently a poly(alkylene oxide) oligomer.
2. The compound of claim 1 , wherein R II is lower alkyl.
3. The compound of claim 2 , wherein R II is ethyl.
4. The compound of claim 3 , wherein R II ″ is hydrogen.
5. The compound of claim 4 , wherein X is a covalent bond.
6. The compound of claim 5 , wherein R II ′ is hydrogen.
7. The compound of claim 6 , wherein Alk is ethylene.
8. The compound of claim 7 , wherein Ar is phenyl.
9. The compound of claim 8 , wherein each poly(alkylene oxide) oligomer is a poly(ethylene glycol) oligomer.
10. The compound of claim 9 , wherein each poly(ethylene glycol) oligomer includes an alkoxy or hydroxyl end-capping moiety.
11. A pharmaceutical composition, comprising a compound of claim 1 and optionally a pharmaceutically acceptable excipient.
12. A dosage form, comprising a compound of claim 1 .
13. 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.
14. The composition of claim 1 , wherein the composition is suitable for oral administration.
15. A method of treating pain in a patient, comprising administering the composition of claim 11 .
16. The compound of claim 10 , wherein the poly(ethylene oxide) oligomer is made of between 2 and 30 monomers.
17. The compound of claim 16 , wherein the poly(ethylene oxide) oligomer is made of between 2 and 10 monomers.