Quinazoline based egfr inhibitors containing a zinc binding moiety

Abstract

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

1 . (canceled) 
     
     
         2 . A compound of the formula 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein A is selected from the group consisting of 
       
       
         
           
           
               
               
           
         
       
     
     
         3 . The compound of  claim 2 , wherein A is 
       
         
           
           
               
               
           
         
       
     
     
         4 . A method of treating a cancer which is mediated by EFGR-tyrosine kinase, HER-2 or HDAC in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound of  claim 1 . 
     
     
         5 . The method of  claim 4 , wherein the cancer is selected from the group consisting of papilloma, glioblastoma, Kaposi's sarcoma, melanoma, non-small cell lung cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, astrocytoma, head cancer, neck cancer, bladder cancer, breast cancer, lung cancer, colorectal cancer, thyroid cancer, pancreatic cancer, gastric cancer, hepatocellular carcinoma, leukemia, lymphoma, Hodgkin's disease and Burkitt's disease. 
     
     
         6 . The method of  claim 4 , wherein the cancer is selected from breast cancer, hepatocellular carcinoma, colon cancer, head and neck cancer, renal carcinoma, lung cancer, prostate cancer, gastric carcinoma, leukemia and pancreatic cancer. 
     
     
         7 . The method of  claim 4 , wherein A is