15962-42-2Relevant articles and documents
Synthesis of Rhodium Complexes with Chiral Diene Ligands via Diastereoselective Coordination and Their Application in the Asymmetric Insertion of Diazo Compounds into E?H Bonds
Ankudinov, Nikita M.,Chusov, Denis A.,Nelyubina, Yulia V.,Perekalin, Dmitry S.
, p. 18712 - 18720 (2021)
A new method for the synthesis of chiral diene rhodium catalysts is introduced. The readily available racemic tetrafluorobenzobarrelene complexes [(R2-TFB)RhCl]2 were separated into two enantiomers via selective coordination of one of them with the auxiliary S-salicyl-oxazoline ligand. One of the resulting chiral complexes with an exceptionally bulky diene ligand [(R,R-iPr2-TFB)RhCl]2 was an efficient catalyst for the asymmetric insertion of diazoesters into B?H and Si?H bonds giving the functionalized organoboranes and silanes with high yields (79–97 %) and enantiomeric purity (87–98 % ee). The stereoselectivity of separation via auxiliary ligand and that of the catalytic reaction was predicted by DFT calculations.
Targeting Her2-insYVMA with Covalent Inhibitors - A Focused Compound Screening and Structure-Based Design Approach
Lategahn, Jonas,Hardick, Julia,Grabe, Tobias,Niggenaber, Janina,Jeyakumar, Kirujan,Keul, Marina,Tumbrink, Hannah L.,Becker, Christian,Hodson, Luke,Kirschner, Tonia,Kl?vekorn, Philip,Ketzer, Julia,Baumann, Matthias,Terheyden, Susanne,Unger, Anke,Weisner, J?rn,Müller, Matthias P.,Van Otterlo, Willem A. L.,Bauer, Sebastian,Rauh, Daniel
, p. 11725 - 11755 (2020/11/26)
Mutated or amplified Her2 serves as a driver of non-small cell lung cancer or mediates resistance toward the inhibition of its family member epidermal growth factor receptor with small-molecule inhibitors. To date, small-molecule inhibitors targeting Her2 which can be used in clinical routine are lacking, and therefore, the development of novel inhibitors was undertaken. In this study, the well-established pyrrolopyrimidine scaffold was modified with structural motifs identified from a screening campaign with more than 1600 compounds, which were applied against wild-type Her2 and its mutant variant Her2-A775_G776insYVMA. The resulting inhibitors were designed to covalently target a reactive cysteine in the binding site of Her2 and were further optimized by means of structure-based drug design utilizing a set of obtained complex crystal structures. In addition, the analysis of binding kinetics and absorption, distribution, metabolism, and excretion parameters as well as mass spectrometry experiments and western blot analysis substantiated our approach.
