Disubstituted phthalazine hedgehog pathway antagonists

• US 7,981,892 B2
• Filed: 04/01/2009
• Issued: 07/19/2011
• Est. Priority Date: 04/29/2008
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Hipskind, Philip Arthur, Wilson (nee Takakuwa), Takako
• Primary Examiner(s): Ward; Paul V.
• Application Number:
  US12/935,655
• Publication Number:
  US 20110046143A1
• Time in Patent Office: 839 Days
• Field of Search: 544/237, 514/248
• US Class Current: 514/248
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond

Abstract

The present invention provides novel 1,4-disubstituted phthalazine hedgehog pathway antagonists useful in the treatment of cancer.

Claims

1. A compound of the following formula:

2. The compound of claim 1 wherein R¹ is hydrogen, or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 wherein R¹ is fluoro, or a pharmaceutically acceptable salt thereof.

4. The compound of claim 2 wherein R² is methyl, or a pharmaceutically acceptable salt thereof.

5. The compound of claim 3 wherein R² is methyl, or a pharmaceutically acceptable salt thereof.

6. The compound of claim 2 wherein R² is hydrogen, or a pharmaceutically acceptable salt thereof.

7. The compound of claim 3 wherein R² is hydrogen, or a pharmaceutically acceptable salt thereof.

8. The compound of claim 4 wherein R³ is chloro, fluoro, trifluoromethyl or trifluoromethoxy, or a pharmaceutically acceptable salt thereof.

9. The compound of claim 5 wherein R³ is chloro, fluoro, trifluoromethyl or trifluoromethoxy, or a pharmaceutically acceptable salt thereof.

10. The compound of claim 6 wherein R³ is chloro, fluoro, trifluoromethyl or trifluoromethoxy, or a pharmaceutically acceptable salt thereof.

11. The compound of claim 7 wherein R³ is chloro, fluoro, trifluoromethyl or trifluoromethoxy, or a pharmaceutically acceptable salt thereof.

12. The compound of claim 8 wherein R⁵ is fluoro, trifluoromethoxy or trifluoromethyl, or a pharmaceutically acceptable salt thereof.

13. The compound of claim 9 wherein R⁵ is fluoro, trifluoromethoxy or trifluoromethyl, or a pharmaceutically acceptable salt thereof.

14. The compound of claim 10 wherein R⁵ is fluoro, trifluoromethoxy or trifluoromethyl, or a pharmaceutically acceptable salt thereof.

15. The compound of claim 11 wherein R⁵ is fluoro, trifluoromethoxy or trifluoromethyl, or a pharmaceutically acceptable salt thereof.

16. The compound of claim 13 which is 4-fluoro-N-(1-(4-(4-fluorophenyl)phthalazin-1-yl)piperidin-4-yl)-N-methyl-2-(trifluoromethyl)benzamide, or a pharmaceutically acceptable salt thereof.

17. A pharmaceutical composition comprising a compound of the formula:

18. The pharmaceutical composition of claim 17 comprising the compound of the formula:

19. The pharmaceutical composition of claim 18 comprising the compound which is 4-fluoro-N-(1-(4-(4-fluorophenyl)phthalazin-1-yl)piperidin-4-yl)-N -methyl-2-(trifluoromethyl)benzamide, or a pharmaceutically acceptable salt thereof.