Disubstituted phthalazine hedgehog pathway antagonists

• US 8,404,687 B2
• Filed: 10/22/2009
• Issued: 03/26/2013
• Est. Priority Date: 11/03/2008
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Bastian, Jolie Anne, Hipskind, Philip Arthur, Sall, Daniel Jon, Wilson (nee Takakuwa), Takako
• Primary Examiner(s): Ward, Paul V.
• Application Number:
  US13/122,212
• Publication Number:
  US 20110190304A1
• Time in Patent Office: 1,251 Days
• Field of Search: 514/248, 544/237
• US Class Current: 514/248
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 403/04 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, fluoro or cyano, or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 2 wherein R¹ is fluoro, or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 wherein R² is hydrogen or fluoro, or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 4 wherein R² is hydrogen, or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 1 wherein R³ is hydrogen, or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1 wherein R⁴ is fluoro, chloro, cyano, trifluoromethoxy, trifluoromethyl or difluoromethoxy, or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 7 wherein R⁴ is fluoro or cyano, or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 1

wherein

10. The compound according to claim 1 which is (S)—

N-(4-Fluorophenyl)-4-(4-(4-fluorophenyl)phthalazin-1-yl)-2-methylpiperazine-1-carboxamide, or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 10 which is (S)—

N-(4-Fluorophenyl)-4-(4-(4-fluorophenyl)phthalazin-1-yl)-2-methylpiperazine-1-carboxamide hydrochloride.

12. A pharmaceutical composition comprising a compound of the following formula:

13. A pharmaceutical composition comprising a compound which is (S)—

N-(4-Fluorophenyl)-4-(4-(4-fluorophenyl)phthalazin-l-yl) -2-methylpiperazine-1-carboxamide, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.