Novel Ezrin Inhibitors and Methods of Making and Using

Abstract

The invention encompasses compound and pharmaceutical composition comprising the compound of the following Formula (I): or pharmaceutically acceptable salts or prodrugs thereof, that are useful for inhibiting ezrin protein in a cell or for inhibiting the growh of a cancer cell.

What is claimed is: 
     
         1 . A compound of 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salts or prodrugs thereof, 
         wherein 
         E, F and G are optionally independently present; 
       
       
         
           
           
               
               
           
         
         wherein 
         Y 1 , Y 2 , Y 3 , and Y 4  are each independently N or C—Z; wherein Z is H or a C 1  to C 6  linear, branched or cyclic alkyl; 
         M and D are not both hydrogen; 
         D is H, halogen, OH, aryl, aryloxy, NO 2 , CN, carboxy, SH, CF 3 , C 1  to C 10  alkoxy, NH 2 , or NR 13 R 14 ; 
         wherein R 13  and R 14  are each independently H, C 1  to C 15  linear chain or branched chain alkyl; 
         when none of E, F and G are present, M is H, halogen, OH, aryl, aryloxy, NO 2 , CN, carboxy, SH, CF 3 , C 1  to C 10  alkoxy, NH 2 , or NR 13 R 14 ; 
         when at least one of E, F and G are present, M is —NH—, —O—, or —S—; 
         E is a bond, linear, branched or cyclic C 1  to C 10  alkylene, alkene, alkyne, or ether; 
         F is a bond, O, S, 
       
       
         
           
           
               
               
           
         
         and 
         G is 
       
       
         
           
           
               
               
           
         
         wherein 
         R 1 -R 12  and X 1 -X 5  are each independently selected from H, halogen, OH, aryl, aryloxy, NO 2 , CN, carboxy, SH, CF 3 , C 1  to C 5  alkoxy, C 1  to C 5  alkyl group, NHCONH 2 , NH—SO 2 CH 3 , NH—NH—NH 2 , NH 2 , or NR 13 R 14 ; 
         with the proviso that when R 3  is OH and 
       
       
         
           
           
               
               
           
         
         R 2  and R 4  are not both H, OH, or the same halogen. 
       
     
     
         2 .- 61 . (canceled) 
     
     
         62 . A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         63 . A method of inhibiting ezrin protein in a cell comprising administering at least one compound of  claim 1 . 
     
     
         64 . The method of  claim 63 , wherein the cell is an abnormal cancer cell. 
     
     
         65 . A method of inhibiting the growth of a cancer cell comprising administering to the cell an amount of at least one compound of  claim 1 . 
     
     
         66 . The method of  claim 65  wherein the cancer cell is selected from the group consisting of a lung cancer cell, a breast cancer cell, a colon cancer cell, a malignant melanoma cell, an ovarian carcinoma cell, a brain tumor cell, a soft tissue sarcoma cell, rhabdomyosarcoma, prostate cancer and pancreas cancerand an osteosarcoma cell. 
     
     
         67 . The method of  claim 66  wherein the cancer cell is an osteosarcoma cell. 
     
     
         68 . The method of  claim 67 , wherein the osteosarcoma cell is in a subject. 
     
     
         69 . A method of reducing the likelihood of cancer metastasis comprising administering to a subject in need of a therapeutically effective amount of at least one compound of  claim 1 . 
     
     
         70 . The method of  claim 69  wherein the cancer is selected from the group consisting of lung cancer, breast cancer, colon cancer, malignant melanoma, ovarian carcinoma, brain tumors, soft tissue sarcomas, rhabdomyosarcoma, prostate cancer and pancreas cancer and osteosarcoma. 
     
     
         71 . The method of  claim 70  wherein the cancer is osteosarcoma.