Oligomer conjugates of heteropentacyclic nucleosides
View Patent ↗The invention provides small molecule drugs that are chemically modified by covalent attachment of a water-soluble oligomer.
1. A method of treating influenza, comprising administering to a patient, a compound having the following structure:
wherein:
R 2 is hydrogen or hydroxyl;
R 3 is hydroxyl when R 2 is hydrogen and R 3 is hydrogen when R 2 is hydroxyl;
(a) is two;
X is an amide linkage; and
each POLY is independently a water-soluble, non-peptidic oligomer, and 5′-phosphates and 3′,5′-cyclic phosphates thereof and ammonium and alkali metal salts of each of the 5′-phosphates and 3′,5′-cyclic phosphates.
2. The method of claim 1 , wherein the weight average molecular weight of each water-soluble, non-peptidic oligomer is less than 400 Daltons.
3. The method of claim 1 , wherein each water-soluble, non-peptidic oligomer is a poly(alkylene oxide).
4. The method of claim 3 , wherein each poly(alkylene oxide) is a poly(ethylene oxide).
5. The method of claim 4 , wherein the poly(ethylene oxide) oligomer has a number of repeating monomers in the range of from 1 to 30.
6. The method of claim 5 , wherein the water-soluble, non-peptidic oligomer has a number of repeating monomers in the range of from 1 to 10.
7. The method of claim 3 , wherein the poly(alkylene oxide) includes an alkoxy or hydroxy end-capping moiety.
8. The method of claim 1 , wherein the compound is administered as part of a composition comprising (i) the compound of claim 1 , and (ii) a pharmaceutically acceptable excipient.
9. The method of claim 1 , wherein a dosage form comprising the compound of claim 1 is administered.
10. The method of claim 1 , wherein the compound is administered orally.
11. The method of claim 8 , wherein the composition is administered orally.
12. The method of claim 1 , wherein the amount of compound administered is in the range of 0.01 mg to 750 mg.
13. The method of claim 1 , wherein the compound is selected from a compound of the formula
wherein for each occurrence, n is an integer from 1 to 15; and 5′-phosphates and 3′,5′-cyclic phosphates thereof and ammonium and alkali metal salts of each of the 5′-phosphates and 3′,5′-cyclic phosphates.
14. The method of claim 13 , wherein for each occurrence, n is an integer from 1 to 10.
15. The method of claim 14 , wherein for each occurrence, n is 5.
16. The method of claim 13 , wherein the compound is administered as part of a composition comprising (i) the compound of claim 13 , and (ii) a pharmaceutically acceptable excipient.
17. The method of claim 13 , wherein the compound is administered orally.
18. The method of claim 16 , wherein the compound is administered orally.
19. The method of claim 13 , wherein the amount of compound administered is in the range of 0.01 mg to 750 mg.