Oligomer-anticholinergic agent conjugates
View Patent ↗The invention provides anticholinergic agents that are chemically modified by covalent attachment of a water-soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different as compared to the characteristics of the anticholinergic agent not attached to the water-soluble oligomer.
1. A compound having the following structure:
wherein:
R 1 is selected from the group consisting of cyclopentyl, 1-hydroxyl cyclopentyl, cyclohexyl and phenyl;
R 2 is selected from the group consisting of —H and —OH;
R 3 is selected from the group consisting of cyclopentyl, 1-hydroxyl cyclopentyl, cyclohexyl and phenyl;
L 2 is selected from the group consisting of hydrocarbon linkers of 2-4 carbons, heterocyclo linkers, and biheterocyclo linkers;
R 5 is selected from the group consisting of —CH 3 and —CH 2 CH 3 ;
X is a spacer moiety; and
POLY is a water-soluble, non-peptidic oligomer,
and charged species of the compound.
2. The compound of claim 1 , wherein R 1 is cyclohexyl, R 2 is —OH, and R 3 is phenyl.
3. The compound of claim 1 , wherein L 2 is —CH 2 —C≡C—CH 2 —.
4. The compound of claim 1 , having the following structure:
wherein (n) is 1-30.
5. The compound of claim 1 , wherein the water-soluble, non-peptidic oligomer is a poly(alkylene oxide).
6. The compound of claim 5 , wherein the poly(alkylene oxide) is a poly(ethylene oxide).
7. The compound of claim 1 , wherein the spacer moiety is a covalent bond.
8. The compound of claim 1 , wherein the water-soluble, non-peptidic oligomer has between 1 and 30 monomers.
9. The compound of claim 8 , wherein the water-soluble, non-peptidic oligomer has between 1 and 10 monomers.
10. The compound of claim 5 , wherein the poly(alkylene oxide) includes an alkoxy or hydroxy end-capping moiety.
11. The compound of claim 1 , wherein the spacer moiety is an ether linkage.
12. The compound of claim 1 , wherein the spacer moiety is an ester linkage.
13. The compound of claim 1 , wherein the spacer moiety is an amine linkage.
14. A composition comprising a compound of claim 1 , and optionally, a pharmaceutically acceptable excipient.
15. A composition of matter comprising a compound of claim 1 , wherein the compound is present in a dosage form.
16. The compound of claim 1 , having the following structure: