| 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 (I), the stereoisomeric forms and salts thereof, wherein n is 1 to 5; &Ugr; is praline, 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 &Ugr; in each repeat of [Y-X] are chosen independently from one another and independently from other repeats; &Zgr; is a direct bond or a bivalent straight or branched saturated hydrocarbon group having from 1 to 4 carbon atoms; Ris an aryl, heteroaryl, aryloxy, heteroaryloxy, aryloxyCalkyl, heterocycloalkyloxy, helerocycloalkylCakloxy, heteroaryloxyCalkyl, heteroarylCalkyloxy; Ris arylCalkyl; Ris Calkyl, Calkenyl or СсусlоаlкуlСаlkyl; Ris hydrogen or Calkyl. The present invention furthermore provides the use of said prodrugs as medicines as well as a method of producing said prodrugs.(I) |
