Alvocidib prodrugs having increased bioavailability
Compounds having the following structure (I): or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein one of R 1 , R 2 or R 3 is —P(═O)(OH) 2 , and the other two of R 1 , R 2 and R 3 are each H, are provided. Pharmaceutical compositions comprising the compounds, and methods for use of the compounds for treating diseases associated with overexpression of a cyclin-dependent kinase (CDK) are also provided.
1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient, and a compound having the following structure:
or a tautomer or pharmaceutically acceptable salt thereof.
2. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral delivery.
3. The pharmaceutical composition of claim 1 , wherein the compound has the following structure:
4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated as a capsule.
5. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable carrier or excipient comprises lactose.
6. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable carrier or excipient comprises microcrystalline cellulose.
7. The pharmaceutical composition of claim 1 , further comprising a glidant.
8. The pharmaceutical composition of claim 7 , wherein the glidant comprises colloidal silicon dioxide.
9. The pharmaceutical composition of claim 1 , further comprising a lubricant.
10. The pharmaceutical composition of claim 9 , wherein the lubricant comprises magnesium stearate.
11. A pharmaceutical composition comprising:
a compound having the following structure:
or a tautomer or pharmaceutically acceptable salt thereof;
a pharmaceutically acceptable carrier or excipient;
a glidant; and
a lubricant.
12. The pharmaceutical composition of claim 11 , wherein the compound has the following structure:
13. The pharmaceutical composition of claim 11 , wherein the pharmaceutical composition is formulated for oral delivery.
14. The pharmaceutical composition of claim 11 , wherein the pharmaceutical composition is formulated as a capsule.
15. The pharmaceutical composition of claim 11 , wherein the pharmaceutically acceptable carrier or excipient comprises lactose.
16. The pharmaceutical composition of claim 11 , wherein the glidant comprises colloidal silicon dioxide.
17. The pharmaceutical composition of claim 11 , wherein the lubricant comprises magnesium stearate.
18. A pharmaceutical composition comprising:
a compound having the following structure:
lactose;
colloidal silicon dioxide; and
magnesium stearate.
19. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition is formulated for oral delivery.
20. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition is formulated as a capsule.