Sterically hindered poly (ethylene glycol) alkanoic acids and derivatives thereof
View Patent ↗The invention provides a sterically hindered polymer that comprises a water-soluble and non-peptidic polymer backbone having at least one terminus covalently bonded to an alkanoic acid or alkanoic acid derivative, wherein the carbon adjacent to the carbonyl group of the acid or acid derivative group has an alkyl or aryl group pendent thereto. The steric effects of the alkyl or aryl group allow greater control of the hydrolytic stability of polymer derivatives. The polymer backbone may be poly(ethylene glycol).
1. A polymer comprising the structure:
wherein:
n is 3 to 4000;
R′ is a capping group or a functional group;
Q is O or S;
(m) is 0 to 20;
Z is selected from the group consisting of alkyl, substituted alkyl, aryl and substituted aryl; and
X is a leaving group.
2. The polymer of claim 1 , wherein n is 3 to 2000.
3. The polymer of claim 1 , wherein Z is a C 1 –C 8 alkyl or substituted alkyl.
4. The polymer of claim 1 , wherein Z is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, and benzyl.
5. The polymer of claim 1 , wherein m is 1 to about 10.
6. The polymer of claim 1 , wherein R′ is a capping group.
7. The polymer of claim 6 , wherein the capping group is methoxy.
8. The polymer of claim 1 , wherein R′ is a functional group.
9. The polymer of claim 8 , wherein R′ is a functional group selected from the group consisting of hydroxyl, protected hydroxyl, active ester, active carbonate, acetal, aldehyde, aldehyde hydrate, alkenyl, acrylate, methacrylate, acrylamide, active sulfone, amine, protected amine, hydrazide, protected hydrazide, thiol, protected thiol, carboxylic acid, protected carboxylic acid, isocyanate, isothiocyanate, maleimide, vinylsulfone, dithiopyridine, vinylpyridine, iodoacetamide, epoxide, glyoxal, dione, mesylate, tosylate, and tresylate.
10. The polymer of claim 1 , wherein the leaving group is —OH.
11. The polymer of claim 1 , wherein the leaving group is halogen.
12. The polymer of claim 11 , wherein the halogen is chlorine.
13. The polymer of claim 11 , wherein the halogen is bromide.
14. The polymer of claim 1 , wherein the leaving group is succinimidyloxy.
15. The polymer of claim 1 , wherein the leaving group is sulfo-N-succinimidyloxy.
16. The polymer of claim 1 , wherein the leaving group is 1-benzotriazolyloxy.
17. The polymer of claim 1 , wherein the leaving group is 1-imidazolyl.
18. The polymer of claim 1 , wherein the leaving group is p-nitrophenyloxy.
19. A compound of the following structure:
wherein n is from 3 to 4000.
20. The compound of claim 19 , wherein n is from 3 to 2000.
21. A compound of the following structure:
wherein n is from 3 to 4000.
22. The compound of claim 21 , wherein n is from 3 to 2000.
23. A compound of the following structure:
wherein n is from 3 to 4000.
24. The compound of claim 23 , wherein n is from 3 to 2000.
25. A compound of the following structure:
wherein n is from 3 to 4000.
26. The compound of claim 25 , wherein n is from 3 to 2000.