Compounds modulating c-kit activity

• US 7,498,342 B2
• Filed: 06/16/2005
• Issued: 03/03/2009
• 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, Zhang, Chao, Ibrahim, Prabha N., Hurt, Clarence R.
• Primary Examiner(s): Seaman; D. Margaret
• Assistant Examiner(s): Rahmani; Niloofar
• Application Number:
  US11/154,988
• Publication Number:
  US 20060058340A1
• Time in Patent Office: 1,356 Days
• Field of Search: 546/113, 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 compound having the structure

2. The compound of claim 1, wherein X¹ is selected from the group consisting of methylene and substituted methylene.

3. The compound of claim 2, wherein X¹ is difluoromethylene.

4. The compound of claim 1, wherein X¹ is —

C(O)—

.

5. The compound of claim 1,

wherein:

X³ is

6. The compound of claim 5, wherein X³ is —

NHCH₂—

.

7. The compound of claim 1, wherein X³ is —

NHC(O)—

.

8. The compound of claim 1,

wherein:

X³ is

9. The compound of claim 1,

wherein:

C² is phenyl;

R^d at each occurrence is independently selected from the group consisting of halogen, lower alkyl, substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted alkylthio, optionally substituted alkenyl, optionally substituted alkyknyl, optionally substituted amine, optionally substituted amido, carboxyl, hydroxyl, optionally substituted aryl, aryloxy, optionally substituted heterocycle, heteroaryl, substituted heteroaryl. nitro, cyano, thiol, and sulfonylamino; and

m is in the range 0-2.

10. The compound of claim 1,

wherein:

C² is selected from the group consisting of thienyl, pyridinyl, pyrimidinyl, pymzinyl, pyridazinyl, pyrrolyl, imidazolyl, and furanyl.

11. A composition comprising a compound according to claim 1