公开(公告)号：US11685714B2

公开(公告)日：2023-06-27

申请号：US16087928

申请日：2017-03-21

申请人： BAYER PHARMA AKTIENGESELLSCHAFT

发明人： Hans-Georg Lerchen ,  Anne-Sophie Rebstock ,  Leo Marx ,  Sarah Anna Liesa Johannes ,  Beatrix Stelte-Ludwig ,  Lisa Dietz ,  Carsten Terjung ,  Christoph Mahlert ,  Simone Greven ,  Anette Sommer ,  Sandra Berndt

IPC分类号： C07D207/335 ,  A61K47/65 ,  A61K47/68 ,  C07D401/12 ,  C07D401/14

CPC分类号： C07D207/335 ,  A61K47/65 ,  A61K47/6803 ,  A61K47/6845 ,  A61K47/6849 ,  A61K47/6889 ,  C07D401/12 ,  C07D401/14

摘要： The invention relates to novel prodrugs or conjugates of the general formula (Ia)




in which cytotoxic drugs, for example kinesin spindle protein inhibitors, are masked with legumain-cleavable groups and hence release the drug, 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.

公开(公告)号：US12059472B2

公开(公告)日：2024-08-13

申请号：US16472634

申请日：2017-12-18

申请人： Bayer Aktiengesellschaft ,  Bayer Pharma Aktiengesellschaft

发明人： Hans-Georg Lerchen ,  Anne-Sophie Rebstock ,  Leo Marx ,  Sarah Anna Liesa Johannes ,  Beatrix Stelte-Ludwig ,  Lisa Dietz ,  Hannah Joerissen ,  Christoph Mahlert ,  Simone Greven ,  Anette Sommer

IPC分类号： A61K47/68 ,  A61K31/402 ,  A61K47/65 ,  A61P35/00 ,  C07D207/335

CPC分类号： A61K47/6803 ,  A61K31/402 ,  A61K47/65 ,  A61K47/6849 ,  A61K47/6855 ,  A61P35/00 ,  C07D207/335

摘要： 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.

公开(公告)号：US11123439B2

公开(公告)日：2021-09-21

申请号：US15739111

申请日：2016-06-20

申请人： Bayer Pharma Aktiengesellschaft

发明人： Hans-Georg Lerchen ,  Anne-Sophie Rebstock ,  Yolanda Cancho Grande ,  Leo Marx ,  Beatrix Stelte-Ludwig ,  Carsten Terjung ,  Christoph Mahlert ,  Simone Greven ,  Anette Sommer ,  Sandra Berndt

IPC分类号： A61K47/68 ,  A61K47/65 ,  A61K31/4025 ,  A61K31/4439

摘要： The present invention relates to novel binder-prodrug conjugates (APDCs) where binders are conjugated with inactive precursor compounds of kinesin spindle protein inhibitors, and to antibody-drug conjugates ADCs and to processes for producing these APDCs and ADCs.