Alvocidib prodrugs having increased bioavailability
View Patent ↗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 method for treating a hematologic cancer in a mammal in need thereof, the method comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a compound of structure (IB′), to the mammal, wherein the compound of structure (IB′) has following structure:
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the hematologic cancer is selected from acute myelogenous leukemia (AML), multiple myeloma, follicular lymphoma, acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma.
3. The method of claim 2 , wherein the hematologic cancer is acute myelogenous leukemia (AML).
4. The method of claim 2 , wherein the hematologic cancer is chronic lymphocytic leukemia (CLL).
5. The method of claim 1 , wherein the hematologic cancer is myelodysplasic syndrome (MDS).
6. The method of claim 1 , wherein the method comprises orally administering the pharmaceutical composition comprising the compound of structure (IB′) to the mammal.
7. The method of claim 1 , wherein the pharmaceutical composition comprises the pharmaceutically acceptable salt of the compound of structure (IB′).
8. The method of claim 7 , wherein the pharmaceutically acceptable salt is a base addition salt.
9. The method of claim 7 , wherein the pharmaceutically acceptable salt is a sodium salt.
10. The method of claim 7 , wherein the pharmaceutically acceptable salt is an acid addition salt.
11. The method of claim 7 , wherein the pharmaceutically acceptable salt is a hydrochloride salt.
12. The method of claim 1 , wherein the hematologic cancer is multiple myeloma.
13. The method of claim 1 , further comprising administering to the mammal one or more additional therapeutic agents.