Substituted Triazolo-Pyrazine Compounds

• US 20110160215A1
• Filed: 12/29/2010
• Published: 06/30/2011
• Est. Priority Date: 12/30/2009
• Status: Active Grant

• Current Assignee: ArQule, Inc. (Merck & Co., Inc.)
• Original Assignee: ArQule, Inc. (Merck & Co., Inc.)
• Inventors: Westlund, Neil
• Granted Patent: US 8,329,705 B2
• Time in Patent Office: Days
• US Class Current: 514/249
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/08 for leprosy
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems

Abstract

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

Claims

1. A compound having formula I:

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

3. The compound of claim 2, wherein R₃ and R₄ are each H.

4. The compound of claim 2, wherein R₃ is C(O)OR₅ and R₄ is H.

5. The compound of claim 4, wherein R₅ is unsubstituted or substituted C₁-C₆ alkyl.

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

7. The compound of claim 6, wherein R₃ is H.

8. The compound of claim 6, wherein R₃ is C(O)OR₅.

9. The compound of claim 8, wherein R₅ is unsubstituted or substituted C₁-C₆ alkyl.

10. The compound of claim 6, wherein Q₁ is a bond, or a methyl, ethyl or a propyl linker.

11. The compound of claim 6, wherein R₂ is H.

12. The compound of claim 6, wherein R₂ is methyl, ethyl, propyl or butyl.

13. The compound of claim 6, wherein R₂ is Q₂-T₂.

14. The compound of claim 6, wherein Q₂ is a bond, or a methyl, ethyl or a propyl linker.

15. The compound of claim 2, having formula III:

16. The compound of claim 15, wherein R₃ is H.

17. The compound of claim 15, wherein R₃ is C(O)OR₅.

18. The compound of claim 15, wherein R₅ is unsubstituted or substituted C₁-C₆ alkyl.

19. The compound of claim 1, selected from:

20. 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.

21. A method of treating a cell proliferative disorder by administering to a subject in need thereof, a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt, prodrug, metabolite, analog or derivative thereof, in combination with a pharmaceutically acceptable carrier, such that the disorder is treated.

22. The method of claim 21, further comprising administering to the subject in need thereof, a second anti-proliferative agent.