Chemical compounds

Abstract

This invention relates to certain unsaturated fatty acid derivatives of therapeutically active 1,3-dioxolane nucleoside analogues and to pharmaceutical formulations containing them. The said derivatives are referred to as “Compounds of formula I” herein. Compounds of formula I can be used in the treatment of a cancerous disease. Treatment of both solid tumours and haematological cancers such as leukaemias, lymphomas and multiple myelomas are included.

1 . A compound having the following formula (I):  
     
       
         
         
             
             
         
       
     
     wherein:  
     R 1  is  
     
       
         
         
             
             
         
       
     
     and R 3  is selected from the group consisting of hydrogen, methyl, trifluoromethyl, fluorine, chlorine, bromine and iodine; and 
 X and Y can be either CH or a N atom with at least one of X or Y being N, and  
 Z and W are each independently Br, Cl, I, F, OR 4  or NHR 4  and at least one of Z and W is either OR 4  or NHR 4 , and R 4  is H or R 5 C(O), R 5 CH 2 OC(O) or R 5 CH 2 NHC(O) where R 5  is a C 7-23  alkenyl of the general formula 
   CH 3 —(CH 2 )n-(CH═CH—CH 2 )m-CH═CH—(CH 2 ) 4 —  (II) 
 wherein m is a number from 0 to 2 and n is a number from 0 to 10,  
 R 2  is H or R 5 C(O), R 5 CH 2 OC(O) or R 5 CH 2 NHC(O) where R 5  is a C 7-23  alkenyl of the general formula 
   CH 3 —(CH 2 )n-(CH═CH—CH 2 )m-CH═CH—(CH 2 ) 4 —  (II) 
 wherein m is a number from 0 to 2 and n is a number from 0 to 10, with the proviso that R 2 , R 3  and R 4  cannot simultaneously be hydrogen, or a pharmaceutically acceptable salt thereof.  
 
   
   
       2 . A compound according to  claim 1 , wherein R 1  is cytosine-analogue  
     
       
         
         
             
             
         
       
     
     wherein R 2  is H or R 5 C(O), R 5 CH 2 OC(O) or R 5 CH 2 NHC(O) and R 4  is H or R 5 C(O), R 5 CH 2 OC(O) or R 5 CH 2 NHC(O) where R 5  is a C 7-23  alkenyl of the general formula 
       CH 3 —(CH 2 )n-(CH═CH—CH 2 )m-CH═CH—(CH 2 ) 4 —  (II) 
     wherein m is a number from 0 to 2 and n is a number from 0 to 10, with the proviso that R 2  and R 4  cannot simultaneously be hydrogen, or a pharmaceutically acceptable salt thereof.  
   
   
       3 . A compound according to  claim 1 , defined as:  
     
       
         
         
             
             
         
       
     
     wherein R 2  is H or R 5 C(O), R 5 CH 2 OC(O) or R 5 CH 2 NHC(O) and R 4  is H or R 5 C(O), R 5 CH 2 OC(O) or R 5 CH 2 NHC(O) where R 5  is a C 7-23  alkenyl of the general formula 
       CH 3 —(CH 2 )n-(CH═CH—CH 2 )m-CH═CH—(CH 2 ) 4 —  (II) 
     wherein m is a number from 0 to 2 and n is a number from 0 to 10, with the proviso that R 2  and R 4  cannot simultaneously be hydrogen, or a pharmaceutically acceptable salt thereof.  
   
   
       4 . A compound according to  claim 1 , selected from the group consisting of:  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof.  
   
   
       5 - 9 . (canceled)  
   
   
       10 . A method for, treating cancer in a subject in need of such treatment, which comprises administering to such subject a therapeutically effective amount of a compound of formula (I) as defined in  claim 1  or a pharmaceutically acceptable salt thereof.  
   
   
       11 . A pharmaceutical preparation, comprising a compound of formula (I) as defined in  claim 1 , and a pharmaceutically acceptable excipient diluent and/or carrier therefor.