Oligomer-beta blocker conjugates
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 a different biological membrane crossing rate as compared to the biological membrane crossing rate of the small molecule drug not attached to the water-soluble oligomer.
1. A method of treating hypertension, cardiac arrhythmia, migraines, congestive heart failure, angina, anxiety, or depression, comprising:
administering an effective amount of a compound of the following formula to a patient in need thereof:
wherein:
R 1 is lower alkyl;
R 2 is hydrogen;
R 3 is H;
R 4 is H;
R 5 is H;
R 6 is H;
R 7 is H;
Ar is
and
where
optionally bears one or more halo, alkyl, alkoxy, or acyl substituents.
2. The method of claim 1 , wherein the compound is according to Formula II:
3. The method of claim 1 , wherein the compound is selected from
4. The method of claim 1 , wherein said administering comprises orally administering the compound.
5. The method of claim 1 , wherein the compound is provided in a composition comprising a pharmaceutically acceptable excipient.
6. The method of claim 1 , wherein the compound is present in a dosage form.
7. The method of claim 6 , wherein the dosage form is selected from a tablet, a caplet, a capsule, a gel cap, a suspension, a solution, an elixir, and a syrup.
8. The method of claim 1 , wherein the effective amount is 0.01 mg/day to 750 mg/day.
9. The method of claim 1 , wherein the effective amount is 0.10 mg/day to 500 mg/day.
10. The method of claim 1 , wherein said administering comprises administering on a dosing schedule selected from five times a day, four times a day, three times a day, twice daily, and once daily.