Boron-based prodrug strategy for increased bioavailability and lower-dosage requirements for drug molecules containing at least one phenol (or aromatic hydroxyl) group
Boron-based prodrugs of phenol- or aromatic hydroxyl group-containing therapeutic molecules (“original drugs”), uses thereof, and methods of making the same, are provided for achieving, for example, improved bioavailability, prolonged retention (e.g., in a circulatory system) and, in particular, significantly lowered therapeutically effective dosage in order to reduce adverse effects while maintaining the desired therapeutic effects of the original drugs.
1. A compound of Formula 29:
wherein R is selected from the group consisting of:
KF 3B ; (HO) 2 B; and NaF 3 B; and
wherein the boron atom is the point of attachment in each R variable substituent, and any salts thereof.
2. The compound of claim 1 , wherein R is
3. The compound of claim 1 , wherein R is: (HO) 2 B.
4. A pharmaceutical composition comprising the compound of claim 1 .
5. A method of treating breast cancer in a mammal in need thereof, the method comprising administering to said mammal the compound of claim 1 in an amount that is therapeutically effective for said treatment.
6. A method of downregulating an estrogen receptor in a mammal in need thereof, the method comprising administering to said mammal the compound of claim 1 in an amount that is therapeutically effective for said downregulation.