2-substituted imidazo[4,5-d]phenanthroline derivatives and their use in the treatment of cancer

Abstract

The present invention provides 2-substituted imidazo[4,5-d]phenanthroline compounds, which are capable of inhibiting proliferation of one or more renal cancer cells, pancreatic cancer cells, prostate cancer cells, colon cancer cells, leukemia cells, brain cancer/tumour cells or non-small cell lung cancer cells.

1 .- 17 . (canceled) 
     
     
         18 . A compound of formula (IV): 
       
         
           
           
               
               
           
         
         or a salt or solvate thereof, wherein:
 one of R 1  and R 2 , or R 2  and R 3 , or R 3  and R 4 , or R 4  and R 5 , when taken together with the carbon atoms, to which they are attached form a 5 or 6 membered optionally substituted heterocycle, having at least one heteroatom that is N or O, 
 and remaining of R1 to R5 are independently H, optionally substituted alkyl, or optionally substituted alkoxy. 
 
       
     
     
         19 . The compound of  claim 18 , wherein one of R 1  and R 2 , or R 2  and R 3 , or R 3  and R 4 , or R 4  and R 5 , when taken together with the carbon atoms to which they are attached, form 
       
         
           
           
               
               
           
         
       
       and wherein R a  and R b  are —R c , halo, or —OR d ,
 where R c  is selected from the group consisting of alkyl, cycloalkyl, heteroalkyl, cycloheteroalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl and R d  is independently hydrogen or R c . 
 
     
     
         20 . The compound of  claim 18 , remaining of R 1  to R 5  are each H. 
     
     
         21 . The compound of  claim 18 , wherein R 2  and R 3  are taken together with the carbon atoms, to which they are attached, form: 
       
         
           
           
               
               
           
         
       
       and R 1 , R 4  and R 5  are each H. 
     
     
         22 . The compound of  claim 18 , wherein R a  and R b  are halo. 
     
     
         23 . The compound of  claim 18 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         24 . A pharmaceutical composition comprising a compound according to  claim 18 , or a salt or solvate thereof, and a pharmaceutically acceptable carrier. 
     
     
         25 . A pharmaceutical composition comprising a compound of  claim 23  or a salt or solvate thereof, and a pharmaceutically acceptable carrier. 
     
     
         26 . A method of inhibiting the proliferation of cancer cells in a subject in need thereof, comprising treating the cancer cells with a compound according to  claim 18 . 
     
     
         27 . The method of  claim 26 , wherein the cancer cells are in vitro. 
     
     
         28 . A method of treating cancer in a mammal, comprising administering to said mammal an effective amount of a compound according to  claim 18 . 
     
     
         29 . The method of  claim 26 , wherein the cancer is renal cancer, pancreatic cancer, prostate cancer, colon cancer, leukemia, lymphoma, brain cancer/tumour or non-small cell lung cancer. 
     
     
         30 . The method of  claim 26 , wherein the cancer is lymphoma. 
     
     
         31 . The method of  claim 28 , wherein the cancer is renal cancer, pancreatic cancer, prostate cancer, colon cancer, leukemia, lymphoma, brain cancer/tumour or non-small cell lung cancer. 
     
     
         32 . The method of  claim 31 , wherein the cancer is lymphoma.