Furan derivatives as ep4 receptor antagonists

• US 20070135503A1
• Filed: 10/15/2004
• Published: 06/14/2007
• Est. Priority Date: 10/16/2003
• Status: Active Grant

• Current Assignee: Asterand UK Acquisition Limited
• Original Assignee: Asterand UK Limited
• Inventors: Clark, David, Hynd, George, Fenton, Garry, Harris, Neil, Coleman, Robert, Oxford, Alexander, Stuttle, Keith, Sutton, Jonathan, Davis, Richard, Clark, Kenneth
• Granted Patent: US 7,569,602 B2
• Time in Patent Office: Days
• US Class Current: 514/381
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• 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 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 307/68 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Abstract

A compound of formula (I):

• • or a salt, solvate and chemically protected form thereof, wherein one of R² and R⁵ is:
  • (i) H or an optionally substituted C_1-4 alkyl group; or
  • (ii) an optionally substituted C_5-7 aryl; and the other of R² and R⁵ is the other group; m and n can be 0 or 1, and m+n=1 or 2
  • R^N is H or optionally substituted C_1-4 alkyl
  • R³ is either: (i) carboxy;
    (ii) a group of formula (II):
    (iii) a group of formula (III):
  • wherein R is optionally substituted C_1-7 alkyl, C_5-20 aryl, or NR^N3R^N4, where R^N3 and R^N4 are independently selected from optionally substituted C_1-4 alkyl; or (iv) tetrazol-5-yl.

Claims

1. A compound of formula (I):

2. A compound according to claim 1, wherein R⁵ is the optionally substituted C_5-7 aryl group and R² is H or the optionally substituted C_1-4 alkyl group.

3. A compound according to claim 2, wherein R² is selected from H or an optionally substituted C_1-3 alkyl group.

4. A compound according to claim 3, wherein R² is a methyl group.

5. A compound according to claim 2, wherein R⁵ is a C₆ aryl group.

6. A compound according to claim 5, wherein R⁵ is preferably phenyl.

7. A compound according to claim 1 wherein the C_5-7 aryl group is substituted by substituents selected from C_1-7 alkoxy groups.

8. A compound according to claim 1 wherein R³ is either:

(i) a group of formula (II);

(ii) a group of formula (III);

9. A compound according to claim 8, wherein R is selected from an optionally substituted C_5-20 aryl group, and an optionally substituted C_5-20 aryl-C_1-7 alkyl group.

10. A compound according to claim 8, wherein R is a C_1-7 alkyl group.

11. A compound according to claim 1, wherein n+m=1.

12. A compound according to claim 11, wherein n is 0 and m is 1.

13. A compound according to claim 1, wherein R^N is H or methyl.

14. The use of a compound according to claim 1 or a pharmaceutically acceptable salt thereof in a method of therapy.

15. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.

16. The use of a compound according to claim 1 or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of a condition alleviated by antagonism of an EP₄ receptor.

17. The use according to claim 16, wherein the condition which can be alleviated by antagonism of an EP₄ receptor is a primary headache disorder.

18. The use according to claim 17, wherein the primary headache disorder is a migraine.