Prodrugs of cytotoxic active agents with enzyme-cleavable groups

摘要

The present invention relates to a new class of prodrugs or conjugates of the general formula (Ia), in which La, n, R and D have the meanings indicated in the description. Wherein the prodrug has a structural pattern that is reduced to an asparagine derivative as a cleavage site for a tumor-associated protease such as legumain, and a cytotoxic activator such as a kinesin spindle protein inhibitor is released by legumain cleavage. Or a complex. The invention further relates to the use of said prodrugs or conjugates for the treatment and / or prevention of diseases and the treatment and / or prevention of diseases, in particular hyperproliferative and / or angiogenic diseases, such as cancer diseases. The use of said prodrugs or conjugates for the manufacture of a medicament for use in a pharmaceutical composition. By reducing the legumain-cleavable substrate peptide sequence to an asparagine derivative as a structural pattern, improved stability in lysosomes of healthy organs is achieved with high antitumor activity. Embedded image