| abstract |
The present invention provides novel prodrugs which are conjugates of a therapeutic compound and peptide, wherein the conjugate can be cleaved by dipeptidyl peptidases, more preferably by CD26, also known as DPPIV (dipeptidyl aminodipeptidase IV). The present prodrugs have the formula the stereoisomeric forms and salts thereof, wherein n is 1 to 5, Y is proline, alanine, hydroxyproline, dihydroxyproline, thiazolidinecarboxylic acid (thioproline), dehydroproline, pipecolinic acid (L-homoproline), azetidinecarboxylic acid, azetidine carboxylic acid valine, leucine, isoleucine and threonine, X is selected from any amino acid in the D or L configuration, X and Y in each repeat of [YX] are selected independently and independently of other repeats, Z is a direct bond or a bivalent straight or branched saturated hydrocarbon group having from 1 to 4 carbon atoms. R 'is an aryl, heteroaryl, aryloxy, heteroaryloxy, aryloxyC 1-4 alkyl, heterocycloalkyloxy, heterocycloalkylC 1-4 alkyloxy, heteroaryloxyCi. 4alkyl, heteroarylC1-4 allyloxy, R4 is arylC1-4 allyl, R4 is C1-10 allyl, C1-4 alkoxy or C3-7 cycloalkylC1-4 allyl, R4 is hydrogen or C1-6alkyl. The present invention further provides the use of the prodrugs as medicine as well as as a method for preparing the prodrugs. |