Compounds modulating c-kit activity and uses therefor

• US 20060058339A1
• Filed: 06/16/2005
• Published: 03/16/2006
• Est. Priority Date: 06/17/2004
• Status: Abandoned Application

• 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.
• Application Number:
  US11/154,287
• Publication Number:
  US 20060058339A1
• Time in Patent Office: Days
• US Class Current: 514/300
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Compounds with generic structure 5-((1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-benzylpyridine-2-amine 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 described.

Claims

1. A compound having the chemical structure of Formula I, and pharmaceutically acceptable salts, prodrugs, or isomers thereof,

2. The compound of claim 1 wherein Z is halogen.

3. The compound of claim 2 wherein Z is chloro.

4. The compound of claim 2 wherein Z is fluoro.

5. The compound of claim 1 wherein Z is selected from the group consisting of methyl, monohalomethyl, dihalomethyl, and trihalomethyl.

6. The compound of claim 5 wherein Z is methyl.

7. The compound of claim 5 wherein Z is trifluoromethyl.

8. A composition comprising

a compound having the chemical structure of Formula I or pharmaceutically acceptable salt, prodrug, or isomer thereof,

wherein

Z is selected from the group consisting-of halogen and optionally halogen substituted methyl, and

a pharmaceutically acceptable carrier.

9. The composition of claim 8 wherein Z is trifluoromethyl.

10. 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 having the chemical structure of Formula I or pharmaceutically acceptable salt, prodrug, or isomer thereof,

wherein;

Z is halogen or optionally halogen substituted methyl.

11. The method of claim 10 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 10 wherein said c-kit mediated disease or condition is selected from the group consisting of arthritis, mastocytosis, asthma, and chronic rhinitis.

14. The method of claim 10 wherein said c-kit mediated disease or condition is selected from the group consisting of a cell proliferative disorder, a fibrotic disorder, and 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 selected from the group consisting of 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, and Schwann cell neoplasia associated with neurofibromatosis.

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

18. The method of claim 11 wherein said c-kit mediated disease or condition is asthma.

19. The method of claim 11 wherein said c-kit mediated disease or condition is an allergic reaction.

20. The method of claim 11 wherein said c-kit mediated disease or condition is inflammatory arthritis.