| 摘要 |
The present invention provides new prodrugs which are conjugates of a therapeutic compound and a peptide wherein the conjugate is cleavable 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, pipecolic acid (L-homoproline), azetidinecarboxylic acid, aziridinecarboxylic acid, glycine, serine, 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 [Y-X] are chosen independently from one another and independently from other repeats; Z is a direct bond or a bivalent straight or branched saturated hydrocarbon group having from 1 to 4 carbon atoms; R<SUP>1 </SUP>is an aryl, heteroaryl, aryloxy, heteroaryloxy, aryloxyC<SUB>1-4</SUB>alkyl, heterocycloalkyloxy, heterocycloalkylC<SUB>1-4</SUB>alkyloxy, heteroaryloxyC<SUB>1-4</SUB>alkyl, heteroarylC<SUB>1-4</SUB>alkyloxy; R<SUP>2 </SUP>is arylC<SUB>1-4</SUB>alkyl; R<SUP>3 </SUP>is C<SUB>1-10</SUB>alkyl, C<SUB>2-6</SUB>alkenyl or C<SUB>3-7</SUB>cycloalkylC<SUB>1-4</SUB>alkyl; R<SUP>4 </SUP>is hydrogen or C<SUB>1-4</SUB>alkyl. The present invention furthermore provides the use of said prodrugs as medicines as well as a method of producing said prodrugs. |
