Anti-cancer phosphonate analogs

• US 7,452,901 B2
• Filed: 04/26/2004
• Issued: 11/18/2008
• Est. Priority Date: 04/25/2003
• Status: Expired due to Fees

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Watkins, William J., Zhang, Lijun, Cho, Aesop, Fardis, Maria, Markevitch, David Y., Chong, Lee S., Kim, Choung U., Lin, Kuei-Ying, Boojamra, Constantine G., Ray, Adrian S., Prasad, Vidya K., Lee, Christopher P., Chen, Xiaowu, Swaminathan, Sundaramoorthi, Kirschberg, Thorsten, Chen, James M., Huang, Alan X., Oare, David A., Zhang, Jennifer R., Cannizzaro, Carina, Pyun, Hyung-Jung, Mackman, Richard L., Nelson, Peter H., Krawczyk, Steven
• Primary Examiner(s): SHIAO, REI TSANG
• Application Number:
  US10/833,293
• Publication Number:
  US 20060079478A1
• Time in Patent Office: 1,667 Days
• Field of Search: 544/254, 514/300
• US Class Current: 514/300
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 47/548 Phosphates or phosphonates, e.g. bone-seeking phospholipids A61K47/544
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom

Abstract

The invention is related to phosphorus substituted anti-cancer compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Claims

1. A method of inhibiting leukemia cells in vitro comprising the step of contacting a sample in need of such treatment with a conjugate or a pharmaceutically acceptable salt or solvate thereof wherein the conjugate is a compound of the formula:

[DRUG]−

(A⁰)_nn;

wherein;

DRUG is a compound of formula 557;

3. The method of claim 1 where the conjugate has fonnula 211 or 212:

4. The method of claim 1 wherein each A³ is of the formula:

5. The method of claim 1 wherein each A³ is of the formula:

6. The method of claim 1 wherein each A³ is of the formula:

7. The method of claim 1 wherein A⁰ is of the formula:

2. A method of treating leukemia in a mammal, comprising administering a conjugate or a pharmaceutically acceptable salt or solvate thereof, to the mammal wherein the conjugate is a compound of formula:

[DRUG]−

(A⁰)_nn;

wherein;

DRUG is a compound of formula 557;

8. The method of claim 2 where the conjugate has formula 211 or 212:

9. The method of claim 2 wherein A⁰ is of the formula:

10. The method of claim 2 wherein each A³ is of the formula:

11. The method of claim 2 wherein each A³ is of the formula:

12. The method of claim 2 wherein each A³ is of the formula:

13. The method of claim 2 wherein the leukemia is acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, or hairy-cell leukemia.