Compounds modulating C-kit activity

• US 7,947,708 B2
• Filed: 10/02/2008
• Issued: 05/24/2011
• Est. Priority Date: 06/17/2004
• Status: Expired due to Fees

• Current Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Original Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Inventors: Zhang, Jiazhong, Hurt, Clarence R., Zhang, Chao, Ibrahim, Prabha N.
• Primary Examiner(s): Andres; Janet L
• Assistant Examiner(s): Rahmani; Niloofar
• Application Number:
  US12/244,730
• Publication Number:
  US 20090105297A1
• Time in Patent Office: 964 Days
• Field of Search: 514/300
• 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 selected from the group consisting of multiple sclerosis, rheumatoid arthritis, thyroid cancer, leukemia, and gastrointestinal tract cancer, said method 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 rheumatoid arthritis.

5. The method of claim 1 wherein said c-Kit mediated disease or condition is leukemia.

6. The method of claim 1 wherein said c-Kit mediated disease or condition is thyroid cancer.

7. The method of claim 1 wherein said mediated disease or condition is cancer of the gastrointestinal tract.

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 selected from the group consisting of multiple sclerosis, rheumatoid arthritis, thyroid cancer, leukemia, and gastrointestinal tract cancer, said method comprising:

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

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

11. The method of claim 10 wherein said improperly regulated kinase signal transduction is of mast cells.

12. The method of claim 9 wherein said c-Kit mediated disease or condition is rheumatoid arthritis.

13. The method of claim 9 wherein said c-Kit mediated disease or condition is leukemia.

14. The method of claim 9 wherein said c-Kit mediated disease or condition is thyroid cancer.

15. The method of claim 9 wherein said c-Kit mediated disease or condition is cancer of the gastrointestinal tract.

16. The method of claim 9 wherein said c-Kit mediated disease or condition is multiple sclerosis.

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

administering to said subject an effective amount of a compound selected from the group consisting of;

benzyl-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine;

(6-Benzylamino-pyridin-3-yl)-(1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone;

[5-(1H-Pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(4-trifluoromethyl-benzyl)-amine;

(4-methoxy-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine;

(4-chloro-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine;

(4-fluoro-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine;

(4-methyl-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine; and

[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-thiophen-2-ylmethyl-amine,

wherein the disease or condition is selected from the group consisting of multiple sclerosis, rheumatoid arthritis, thyroid cancer, leukemia, and gastrointestinal tract cancer.

18. The method of claim 17, wherein said c-Kit mediated disease or condition is rheumatoid arthritis.

19. The method of claim 17, wherein said c-Kit mediated disease or condition is a thyroid cancer.

20. The method of claim 17, wherein said c-Kit mediated disease or condition is a cancer of the gastrointestinal tract.

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

22. The method of claim 17, wherein said c-Kit mediated disease or condition is leukemia.