Polymer-sunitinib conjugates
The invention relates to (among other things) polymer-sunitinib conjugates and related compounds. A compound of the invention, when administered by any of a number of administration routes, exhibits advantages over sunitinib in unconjugated form.
1. A compound of Formula IV-C:
wherein:
Xr is a releasable linkage-containing spacer moiety that includes a releasable thioether, carbamate, ester, carbonate, urea, or enzyme-cleavable peptidic linkage; and
POLY is a poly(alkylene oxide) having a number of monomers from about 100 to about 2270,
or pharmaceutically acceptable salts thereof.
2. The compound of claim 1 , wherein the poly(alkylene oxide) is a poly(ethylene oxide).
3. The compound of claim 1 , wherein POLY is linear.
4. The compound of claim 1 , wherein POLY is branched.
5. A compound having a structure represented by:
wherein:
R is a polyol, polythiol or polyamine bearing from 3 to about 50 hydroxyl, thiol or amino groups;
each Xr is a releasable linkage-containing spacer moiety including a releasable thioether, carbamate, ester, carbonate, urea, or enzyme-cleavable peptidic linkage;
each POLY is a poly(alkylene oxide) having a number of monomers from about 100 to about 2270;
each Q is a linker connecting R to POLY, wherein Q comprises 1 to 10 atoms, at least one of which is a heteroatom selected from O, S or N; and
q is a positive integer from 3 to about 50,
or pharmaceutically acceptable salts thereof.
6. The compound of claim 1 , wherein POLY has a molecular weight of less than 2000 Daltons.
7. The compound of claim 1 , wherein POLY has from about 136 to about 2050 monomers.
8. The compound of claim 1 , wherein POLY has from about 225 to about 1930 monomers.
9. The compound of claim 1 , wherein POLY has a molecular weight of from 2000 Daltons to about 150,000 Daltons.
10. The compound of claim 1 , wherein POLY includes an alkoxy or hydroxy end-capping moiety.
11. A composition comprising (i) the compound of claim 1 , and (ii) a pharmaceutically acceptable excipient.
12. The composition of claim 11 formulated in a dosage form.
13. The compound of claim 5 , wherein the poly(alkylene oxide) is a poly(ethylene glycol).
14. The compound of claim 5 , wherein Q is selected from O, S, —NH—, —NH—C(O)—, —OCH2—, and —C(O)—NH—.
15. The compound of claim 1 , wherein the poly(alkylene oxide) is a poly(ethylene glycol).
16. A method of treatment of colorectal cancer comprising administering a pharmacologically effective amount of the compound of claim 1 , to a subject in need thereof.