In 2017,Heinzlmeir, Stephanie; Lohse, Jonas; Treiber, Tobias; Kudlinzki, Denis; Linhard, Verena; Gande, Santosh Lakshmi; Sreeramulu, Sridhar; Saxena, Krishna; Liu, Xiaofeng; Wilhelm, Mathias; Schwalbe, Harald; Kuster, Bernhard; Medard, Guillaume published 《Chemoproteomics-Aided Medicinal Chemistry for the Discovery of EPHA2 Inhibitors》.ChemMedChem published the findings.Application In Synthesis of trans-4-Aminocyclohexanol The information in the text is summarized as follows:
The receptor tyrosine kinase EPHA2 has gained attention as a therapeutic drug target for cancer and infectious diseases. However, EPHA2 research and EPHA2-based therapies have been hampered by the lack of selective small-mol. inhibitors. Herein we report the synthesis and evaluation of dedicated EPHA2 inhibitors based on the clin. BCR-ABL/SRC inhibitor dasatinib as a lead structure. We designed hybrid structures of dasatinib and the previously known EPHA2 binders CHEMBL249097, PD-173955, and a known EPHB4 inhibitor in order to exploit both the ATP pocket entrance as well as the ribose pocket as binding epitopes in the kinase EPHA2. Medicinal chem. and inhibitor design were guided by a chem. proteomics approach, allowing early selectivity profiling of the newly synthesized inhibitor candidates. Concomitant protein crystallog. of 17 inhibitor co-crystals delivered detailed insight into the at. interactions that underlie the structure-affinity relationship. Finally, the anti-proliferative effect of the inhibitor candidates was confirmed in the glioblastoma cell line SF-268. In this work, we thus discovered a novel EPHA2 inhibitor candidate that features an improved selectivity profile while maintaining potency against EPHA2 and anticancer activity in SF-268 cells. After reading the article, we found that the author used trans-4-Aminocyclohexanol(cas: 27489-62-9Application In Synthesis of trans-4-Aminocyclohexanol)
trans-4-Aminocyclohexanol(cas: 27489-62-9) belongs to anime. To avoid the problem of multiple alkylation, methods have been devised for “blocking” substitution so that only one alkyl group is introduced. The Gabriel synthesis is one such method; it utilizes phthalimide, C6H4(CO)2NH, whose one acidic hydrogen atom has been removed upon the addition of a base such as KOH to form a salt.Application In Synthesis of trans-4-Aminocyclohexanol
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