Inhibitors of c-Jun N-terminal kinases for the treatment of neurodegenerative disorders relating to apoptosis and/or inflammation

• US 7,645,769 B2
• Filed: 08/04/2006
• Issued: 01/12/2010
• Est. Priority Date: 08/05/2005
• Status: Expired due to Fees

• Current Assignee: Eisai R & D Management Company Limited (Eisai Medical Research Incorporated)
• Original Assignee: Eisai R & D Management Company Limited (Eisai Medical Research Incorporated)
• Inventors: Medland, Darren Peter, Khan, Afzal, Bhatia, Gurpreet Singh
• Primary Examiner(s): Andres; Janet L
• Assistant Examiner(s): O DELL, DAVID K
• Application Number:
  US11/499,334
• Publication Number:
  US 20070072896A1
• Time in Patent Office: 1,257 Days
• Field of Search: 546/113, 514/300
• US Class Current: 514/300
• 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: C07D 471/04 Ortho-condensed systems

Abstract

The present invention provides novel compounds of formula I and their use in the inhibition of c-Jun N-terminal kinases. The present invention further provides the use of these compounds in medicine, in particular in the prevention and/or treatment of neurodegenerative disorders related to apoptosis and/or inflammation.

Claims

1. A compound of formula (I):

2. A compound as claimed in claim 1 wherein R¹ is an unbranched alkyl group having 2, 3, 4, 5 or 6 carbon atoms.

3. A compound as claimed in claim 1 wherein R¹ is an unbranched alkenyl or alkynyl group having 2, 3, 4, 5 or 6 carbon atoms.

4. A compound as claimed in claim 1 wherein R¹ is a C₅ or C₆ cycloalkyl or phenyl or naphthyl optionally substituted with one or more of C_1-4 alkyl or a halogen.

5. A compound as claimed in claim 4 wherein R¹ is phenyl, in which the phenyl is substituted at the ortho or para position.

6. A compound as claimed in claim 4 wherein R¹ is phenyl.

7. A compound as claimed in claim 1 wherein R² is substituted with C_1-6 alkyl at any available N.

8. A compound as claimed in claim 1 wherein R² is optionally substituted with an alkyl group having 1, 2, 3, 4, 5 or 6 carbon atoms.

9. A compound as claimed in claim 8 wherein said optional substitution of claim 10 occurs at any available N in the pyrazole of R₂.

10. A compound as claimed in claim 8 wherein R² is C_1-6alkylmorpholinyl.

11. A compound of formula II

12. A compound as claimed in claim 11 wherein R¹ is a branched alkyl having 3, 4, 5 or 6 carbon atoms.

13. A compound selected from

14. A composition comprising a compound as defined in claim 13 in combination with a pharmaceutically acceptable carrier, diluent or excipient.