Oligomer-protease inhibitor conjugates
View Patent ↗The invention provides small molecule drugs 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 from the small molecule drug not attached to the water-soluble oligomer.
1. A compound of the following Formula
wherein:
X is a stable amide linkage;
POLY is a poly(alkylene oxide) of between 1 and 30 monomers;
and R 1 is benzyloxycarbonyl or 2-quinolylcarbonyl.
2. The compound of claim 1 , wherein R 1 is benzyloxycarbonyl.
3. The compound of claim 1 , wherein R 1 is 2-quinolylcarbonyl.
4. The compound of claim 1 , wherein the poly(alkylene oxide) is a poly(ethylene oxide).
5. The compound of claim 1 , wherein the water-soluble, non-peptidic oligomer is made of between 1 and 10 monomers.
6. The compound of claim 4 , wherein the poly(alkylene oxide) includes an alkoxy or hydroxy end-capping moiety.
7. The compound of claim 1 , wherein R 1 is benzyloxycarbonyl, the water-soluble, non-peptidic oligomer is a poly(ethylene oxide) made of between 1 and 10 monomers and includes a methoxy end-capping moiety, and the stable linkage is an amide.
8. The compound of claim 1 , wherein R 1 is 2-quinolylcarbonyl, the water-soluble, non-peptidic oligomer is a poly(ethylene oxide) made of between 1 and 10 monomers and includes a methoxy end-capping moiety, and the stable linkage is an amide.
9. A composition comprising a compound of claim 1 , and optionally, a pharmaceutically acceptable excipient.
10. A composition of matter comprising a compound of claim 1 , wherein the compound is present in a dosage form.
11. A method of inhibiting protease activity in a subject in need thereof, the method comprising administering a compound of claim 1 .
12. A compound of the following formula:
wherein n is 3.
13. A compound of the following formula:
wherein n is 5.