SUBSTITUTED PYRAZOLO-PYRROLO-PYRIDINE-DIONE COMPOUNDS

• US 20100249120A1
• Filed: 03/31/2010
• Published: 09/30/2010
• Est. Priority Date: 03/31/2009
• Status: Active Grant

• Current Assignee: ArQule, Inc. (Merck & Co., Inc.)
• Original Assignee: ArQule, Inc. (Merck & Co., Inc.)
• Inventors: Tandon, Manish, Hill, Jason, Westlund, Neil, Filikov, Anton, Palma, Rocio, Namdev, Nivedita
• Granted Patent: US 8,906,928 B2
• Time in Patent Office: Days
• US Class Current: 514/228.500
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 471/14 Ortho-condensed systems

Abstract

The present invention relates to substituted pyrazolo-pyrrolo-pyridine-dione compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted pyrazolo-pyrrolo-pyridine-dione compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds or pharmaceutical compositions to subjects in need thereof.

Claims

1. A compound having formula I:

2. The compound of claim 1, having formula II:

3. The compound of claim 2, wherein R₂ and R₃ are both H.

4. The compound of claim 2, wherein R₂ is fluorine, chlorine, bromine or iodine.

5. The compound of claim 2, wherein R₂ is unsubstituted or substituted phenyl.

6. The compound of claim 2, wherein R₂ is unsubstituted or substituted naphthyl.

7. The compound of claim 2, wherein R₂ is unsubstituted or substituted heteroaryl.

8. The compound of claim 2, wherein n is 0, 1, 2 or 3.

9. The compound of claim 2, having formula:

10. The compound of claim 9, wherein n is 0, 1, 2 or 3.

11. The compound of claim 1, having formula III:

12. The compound of claim 11, wherein R₂ and R₃ are both H.

13. The compound of claim 11, wherein n is 0, 1, 2 or 3.

14. The compound of claim 11, having formula:

15. The compound of claim 14, wherein n is 0, 1, 2 or 3.

16. The compound of claim 1, selected from:

17. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1, or a salt, solvate, hydrate or prodrug thereof, and a pharmaceutically acceptable carrier or excipient.

18. A method of treating a cell proliferative disorder comprising administering to a subject in need thereof a therapeutically effective amount of the composition of claim 17.

19. The method of claim 18, wherein said cell proliferative disorder is selected from a precancerous condition, a hematologic tumor or malignancy, a solid tumor and a cancer.

20. The method of claim 18, wherein said subject is a human.