Compounds Modulating C-Kit Activity

• US 20090105297A1
• Filed: 10/02/2008
• Published: 04/23/2009
• Est. Priority Date: 06/17/2004
• Status: Active Grant

• Current Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Original Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Inventors: Zhang, Jiazhong, Zhang, Chao, Ibrahim, Prabha N., Hurt, Clarence R.
• Granted Patent: US 7,947,708 B2
• Time in Patent Office: Days
• US Class Current: 514/300
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48

Abstract

Compounds with 7-azaindole core structure with activity toward the receptor protein tyrosine kinase c-kit, compositions useful for treatment c-kit-mediate diseases or conditions, and methods of use thereof, are provided. Further provided are methods of c-kit ligand identification and design.

Claims

1. A method for treating a subject suffering from or at risk of a c-Kit mediated disease or condition, comprising:

administering to said subject an effective amount of a compound of

2. The method of claim 1 wherein said c-Kit mediated disease or condition is associated with improperly regulated kinase signal transduction.

3. The method of claim 2 wherein said improperly regulated kinase signal transduction is of mast cells.

4. The method of claim 1 wherein said c-Kit mediated disease or condition is mastocytosis, asthma, rheumatoid arthritis or chronic rhinitis.

5. The method of claim 1 wherein said c-Kit mediated disease or condition is a cell proliferative disorder, a fibrotic disorder, or a metabolic disorder.

6. The method of claim 5 wherein said cell proliferative disorder is cancer.

7. The method of claim 6 wherein said cancer is leukemia, mast cell tumor, small cell lung cancer, testicular cancer, cancer of the gastrointestinal tract, cancer of the central nervous system, cancer of the female genital tract, sarcoma of neuroectodermal origin, or Schwann cell neoplasia associated with neurofibromatosis.

8. The method of claim 1 wherein said c-Kit mediated disease or condition is multiple sclerosis.

9. A method for treating a subject suffering from or at risk of a c-Kit mediated disease or condition, comprising:

administering to said subject an effective amount of a compound having a structure;

10. The method of claim 9, provided, however, that when X¹—

X²—

X³—

X⁴ is

11. The method of claim 9 wherein said c-Kit mediated disease or condition is associated with improperly regulated kinase signal transduction.

12. The method of claim 11 wherein said improperly regulated kinase signal transduction is of mast cells.

13. The method of claim 9 wherein said c-Kit mediated disease or condition is mastocytosis, asthma, or chronic rhinitis.

14. The method of claim 9 wherein said c-Kit mediated disease or condition is a cell proliferative disorder, a fibrotic disorder, or a metabolic disorder.

15. The method of claim 14 wherein said cell proliferative disorder is cancer.

16. The method of claim 15 wherein said cancer is leukemia, mast cell tumor, small cell lung cancer, testicular cancer, cancer of the gastrointestinal tract, cancer of the central nervous system, cancer of the female genital tract, sarcoma of neuroectodermal origin, or Schwann cell neoplasia associated with neurofibromatosis.

17. The method of claim 10 wherein said c-Kit mediated disease or condition is multiple sclerosis.