公开(公告)号：US20230118911A1

公开(公告)日：2023-04-20

申请号：US17906184

申请日：2021-03-10

申请人： Julius-Maximilians-Universitaet Wuerzburg

发明人： Elmar WOLF ,  Martin EILERS

IPC分类号： A61K47/55 ,  A61K47/54 ,  A61P35/00

摘要： The invention concerns a Proteolysis Targeting Chimera (PROTAC) or a pharmaceutically acceptable salt thereof for degradation of Aurora A-kinase in cells of a mammal which PROTAC has the chemical structure AAB-L-E3B, wherein AAB is a binding unit for Aurora A-kinase, L is a linker and E3B is a binding unit for E3-ubiquitin ligase Cereblon, wherein E3B comprises the structure of thalidomide or of one of its analogs lenalidomide, pomalidomide, and apremilast, wherein L comprises or consists of an alkyl ether residue or a polyalkyl ether residue or an alkyl ether residue or a polyalkyl ether residue in which at least one C—C bond is replaced by a C═C double bond, which polyalkyl ether residue has at least two ether groups or at least two ether groups in which one O-atom is replaced by an S-atom or a part of the O-atoms is replaced by S-atoms or wherein L comprises or consists of an alkyl thioether residue or a polyalkyl thioether residue or an alkyl thioether residue or a polyalkyl thioether residue in which at least one C—C bond is replaced by a C═C double bond, which polyalkyl thioether residue has at least two thioether groups, wherein L connects AAB and E3B via a chain of atoms having five to thirteen subsequently arranged atoms, wherein atoms of functional groups connecting the linker with AAB and E3B are not considered as part of said chain.