Analogues of etoposide for the treatment of tumours

Abstract

wherein X is O, NH and S, wherein n is 0, 1 or 2, wherein R1 and R2 are H, methyl or ethyl, or together form a group CR3R4, and wherein R3 and R4 are H, methyl or ethyl.

1 . A method of treating a tumor that is metastatic and/or that reduces an organ function in a subject, wherein said method comprises administering to the subject a compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein X is selected from the group consisting of O, NH and S, 
         n is 0, 1 or 2, and 
         R 1  and R 2  are independently selected from the group consisting of H, methyl, and ethyl, or together form a group CR 3 R 4  wherein R 3  and R 4  are independently selected from the group consisting of H, methyl and ethyl. 
       
     
     
         2 . The method of  claim 1 , wherein said method comprises administering to a subject in need of such treatment a compound selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 1 , wherein the subject is a human. 
     
     
         4 . The method of  claim 1 , wherein the tumor is resistant to treatment with a therapeutic protein or a chemotherapeutic drug exclusive of the compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein X is selected from the group consisting of O, NH and S, 
         n is 0, 1 or 2, and 
         R 1  and R 2  are independently selected from the group consisting of H, methyl, and ethyl, or together form a group CR 3 R 4  wherein R 3  and R 4  are independently selected from the group consisting of H, methyl and ethyl. 
       
     
     
         5 . The method of  claim 1 , wherein the tumor is a solid tumor. 
     
     
         6 . The method of  claim 5 , wherein the tumor is selected from the group consisting of adenocarcinoma, hypopharynx cancer, lung cancer, diffuse large cell lymphoma, Burkitt's lymphoma, Hodgkin lymphoma, Non-Hodgkin lymphoma, histiocytic lymphoma, lymphatic lymphoma, acute T-cell leukemia, pre-B-acute lymphoblastic leukemia, gall bladder cancer, bile duct carcinoma, thymus carcinoma, urothelium carcinoma, testicular cancer, prostate cancer, bladder cancer, brain tumor, AIDS-related Kaposi's sarcoma, Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, ovarian cancer, breast cancer, and unknown primary origin (CUP) syndrome. 
     
     
         7 . The method of  claim 1 , wherein the treatment leads to a stagnation of tumor growth or a remission of the tumor. 
     
     
         8 . The method of  claim 1 , wherein said tumor reduces an organ function. 
     
     
         9 . The method of  claim 1 , wherein the tumor expresses at least one of CES1 and CES2. 
     
     
         10 . The method of  claim 9 , wherein a fraction of CES1 and/or CES2 expressing cells of the tumor is 50% or higher. 
     
     
         11 . The method of  claim 1 , further comprising administering to the subject a second therapeutic drug compound.