DISUBSTITUTED PHTHALAZINE HEDGEHOG PATHWAY ANTAGONISTS

• US 20110190304A1
• Filed: 10/22/2009
• Published: 08/04/2011
• Est. Priority Date: 11/03/2008
• Status: Active Grant

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Hipskind, Philip Arthur, Wilson (nee Takakuwa), Takako, Sall, Daniel Jon, Bastian, Jolie Anne
• Granted Patent: US 8,404,687 B2
• Time in Patent Office: Days
• 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 difluoromethyl, 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 according to claim 1, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.

13. A method of treating brain cancer, basal cell carcinoma, esophagus cancer, gastric cancer, pancreatic cancer, biliary tract cancer, prostate cancer, breast cancer, small-cell lung cancer, non-small cell lung cancer, B-cell lymphoma, multiple myeloma, ovarian cancer, colorectal cancer, liver cancer, kidney cancer or melanoma in a mammal comprising administering to a mammal in need of such treatment an effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.

16. A pharmaceutical composition comprising a compound of claim 10, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, diluent or excipient.

14-15. -15. (canceled)