1616557-92-6Relevant articles and documents
Towards the next generation of dual Bcl-2/Bcl-xL inhibitors
Varnes, Jeffrey G.,Gero, Thomas,Huang, Shan,Diebold, R. Bruce,Ogoe, Claude,Grover, Paul T.,Su, Mei,Mukherjee, Prasenjit,Saeh, Jamal Carlos,Macintyre, Terry,Repik, Galina,Dillman, Keith,Byth, Kate,Russell, Daniel John,Ioannidis, Stephanos
, p. 3026 - 3033 (2014/06/24)
Structural modifications of the left-hand side of compound 1 were identified which retained or improved potent binding to Bcl-2 and Bcl-x L in in vitro biochemical assays and had strong activity in an RS4;11 apoptotic cellular assay. For example, sulfoxide diastereomer 13 maintained good binding affinity and comparable cellular potency to 1 while improving aqueous solubility. The corresponding diastereomer (14) was significantly less potent in the cell, and docking studies suggest that this is due to a stereochemical preference for the RS versus SS sulfoxide. Appending a dimethylaminoethoxy side chain (27) adjacent to the benzylic position of the biphenyl moiety of 1 improved cellular activity by approximately three-fold, and this activity was corroborated in cell lines overexpressing Bcl-2 and Bcl-xL.
