Quinazoline based EGFR inhibitors containing a zinc binding moiety

• US 8,604,044 B2
• Filed: 09/10/2007
• Issued: 12/10/2013
• Est. Priority Date: 09/11/2006
• Status: Expired due to Fees

• Current Assignee: Curis, Inc.
• Original Assignee: Curis, Inc.
• Inventors: Qian, Changgeng, Cai, Xiong, Gould, Stephen, Zhai, Haixiao
• Primary Examiner(s): MCDOWELL, BRIAN E
• Application Number:
  US11/852,604
• Publication Number:
  US 20080194578A1
• Time in Patent Office: 2,283 Days
• Field of Search: 544/293
• US Class Current: 514/266.4
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• 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 239/94 Nitrogen atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to quinazoline containing zinc-binding moiety based derivatives of Formula (IV) below.

These compounds have enhanced and unexpected properties as inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and are useful in the treatment of EGFR-TK related diseases and disorders such as cancer. These compounds may further act as HDAC inhibitors.

Claims

1. A compound represented by the formula (IV):

2. A compound according to claim 1 represented by formula (V):

3. A compound according to claim 1 represented by formula (VI):

4. A pharmaceutical composition comprising as an active ingredient a compound of claim 1 and a pharmaceutically acceptable carrier.

10. The compound of claim 1 represented by Formula VIII:

11. A compound according to claim 1 selected from the compounds delineated in Table A or a pharmaceutically acceptable salt or solvate thereof:

12. The compound of claim 1 represented by Formula X,

5. A compound represented by formula (IV):

6. A compound according to claim 5 represented by formula (V):

7. A compound according to claim 5 represented by formula (VI):

8. A compound according to claim 5 selected from the compounds delineated in the table below or a pharmaceutically acceptable salt or solvate thereof:

9. A pharmaceutical composition comprising as an active ingredient a compound of claim 5 and a pharmaceutically acceptable carrier.