Minimally toxic prodrugs

Abstract

The present invention relates to the field of oligopeptide prodrugs that are intended for the treatment of cancer. The selectivity of these prodrugs requires the presence of an (oligo)peptidic moiety and/or a protective capping group to ensure the prod-rug stability in blood. It further in particular relates to the exemplary oligopeptidic moiety ALGP and to prodrugs comprising it. In particular it also relates to the capping group phosphonoacetyl and to prodrugs comprising this capping group.

1 . A prodrug having the general structure:
   [C x -OP] y -D,   wherein
 C is a capping group; 
 OP is an oligopeptidic moiety; 
 D is a drug; 
 x is an integer being at least 1 when y=1; 
 y is an integer being at least 1, if y is greater than 1, then at least 1 OP is carrying a capping group; and 
   wherein the linkage between C and OP and the linkage between OP and D is direct or via a linker or spacing group, and wherein, if y is greater than 1, the multiple OP moieties are individually linked to each other directly or via a linker or spacing group and/or are individually linked to D directly or via a linker or spacing group;   or a pharmaceutically acceptable salt thereof.   
     
     
         2 - 13 . (canceled) 
     
     
         14 . A method for treating a tumor or cancer in a subject, said method comprising administering to a subject having cancer an amount of prodrug or salt thereof according to  claim 1  sufficient to provide a therapeutically effective amount of drug in the vicinity of the tumor or cancer, said administering resulting in the treatment of said tumor or cancer. 
     
     
         15 - 17 . (canceled) 
     
     
         18 . A method for producing the prodrug according to, said method comprising the steps of:
 (i) obtaining the drug;   (ii) linking the drug to a capped oligopeptidic moiety, resulting m the prodrug; or, alternatively,   (ii′) linking the drug to an oligopeptidic moiety followed by linking the capping group to the oligopeptidic moiety, resulting in the prodrug; and   (iii) purifying the prodrug obtained in step (ii) or (ii′).   
     
     
         19 - 30 . (canceled)