Prodrugs of cytotoxic active agents having enzymatically cleavable groups

US12059472B2 · kind B2 · utility

Assignees

• BAYER HEALTHCARE LLC · DE
• Bayer Pharma Aktiengesellschaft · DE

Inventors

• Hans-Georg Lerchen · Leverkusen, DE
• Anne-Sophie REBSTOCK · Écully, FR
• Leo MARX · Wuppertal, DE
• Sarah Anna Liesa Johannes · Düsseldorf, DE
• Beatrix Stelte-Ludwig · Wülfrath, DE
• Lisa DIETZ · Wuppertal, DE
• Hannah Joerissen · Heiligenhaus, DE
• Christoph MAHLERT · Wuppertal, DE
• Simone Greven · Dormagen, DE
• Anette SOMMER · Berlin, DE

Key dates

• Filing date: Dec 18, 2017
• Grant date: Aug 13, 2024
• Expiry date: Nov 14, 2040

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D207/335
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention relates to novel prodrugs or conjugates of the general formula (Ia) in which La, n, R and D have the definitions given in the description and which have a structural motif reduced to an asparagine derivative as cleavage site for tumour-associated proteases such as legumain, in which cytotoxic drugs, for example kinesin spindle protein inhibitors, are released by legumain cleavage, and to the use of these prodrugs or conjugates for treatment and/or prevention of diseases, and to the use of these prodrugs or conjugates for production of medicaments for treatment and/or prevention of diseases, especially of hyperproliferative and/or angiogenic disorders, for example cancers. Reduction of the legumain-cleavable substrate peptide sequence to an asparagine derivative as structural motif, as a result of slowed legumain cleavage, achieves an increase in stability in the lysosomes of healthy organs while simultaneously maintaining the high anti-tumour effect.