Imidazo[1,2-beta]pyridazine and pyrazolo[1,5-alpha]pyrimidine derivatives and their use as protein kinase inhibitors

• US 7,750,007 B2
• Filed: 11/06/2007
• Issued: 07/06/2010
• Est. Priority Date: 11/06/2006
• Status: Active Grant

• Current Assignee: Sumitomo Pharma Oncology Incorporated (Sumitomo Chemical Company Limited)
• Original Assignee: Supergen Incorporated (Otsuka Holdings Company Limited)
• Inventors: Xu, Yong, Liu, Xiao-Hui, Bearss, David J., Vankayalapati, Hariprasad
• Primary Examiner(s): Berch; Mark L
• Assistant Examiner(s): Jaisle; Cecilia M
• Application Number:
  US11/935,959
• Publication Number:
  US 20080261988A1
• Time in Patent Office: 973 Days
• Field of Search: 544/236, 514/247, 514/248
• US Class Current: 514/248
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The present invention provides protein kinase inhibitors comprising imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine compounds of the following structure (I) and (II):

or a stereoisomer, prodrug or pharmaceutically acceptable salt thereof, wherein R, R₁, R₂ and X are as defined herein. Compositions and methods for using the same in the treatment of cancer and other Pim kinase-associated conditions are also disclosed.

Claims

1. A compound having a structure according to structure (I) below:

2. The compound of claim 1 wherein R is hydrogen.

3. The compound of claim 1 wherein R is methyl.

4. The compound of claim 1 wherein R₁ is substituted phenyl having at least one p, o or m substituent selected from —

OCF₃, —

OCHF₂, —

CF₃, —

OCH₃, and —

OH.

5. The compound of claim 1 wherein R₁ is selected from:

6. The compound of claim 1 wherein R₂ is substituted —

(CH₂)_1,2-piperid-4-yl or substituted —

(CH₂)_1,2-piperazin-1-yl having one or two substituents selected from alkyl.

7. The compound of claim 6 wherein R₂ is selected from:

8. The compound of claim 1, wherein the compound is:

N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)-phenyl)imidazo[1,2-b]pyridazin-6-amine (Compound 7-29);

N-(2-(4-methylpiperazin-1-yl)butyl)-3-(3-(trifluoromethoxy)-phenyl)imidazo[1,2-b]pyridazin-6-amine (Compound 7-31);

7-methyl-N-((1-methylpiperidin-4-yl)methyl)-3-(3-trifluoromethoxy)-phenyl)imidazo[1,2-b]pyridazin-6-amine (Compound 7-37);

or

N-((1-ethylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)-phenyl)imidazo[1,2-b]pyridazin-6-amine (Compound 7-39).

9. A composition comprising a compound of claim 1 in combination with a pharmaceutically acceptable excipient.