243984-48-7Relevant academic research and scientific papers
Structure-Guided Synthesis and Mechanistic Studies Reveal Sweetspots on Naphthyl Salicyl Hydrazone Scaffold as Non-Nucleosidic Competitive, Reversible Inhibitors of Human Ribonucleotide Reductase
Huff, Sarah E.,Mohammed, Faiz Ahmad,Yang, Mu,Agrawal, Prashansa,Pink, John,Harris, Michael E.,Dealwis, Chris G.,Viswanathan, Rajesh
supporting information, p. 666 - 680 (2018/02/16)
Ribonucleotide reductase (RR), an established cancer target, is usually inhibited by antimetabolites, which display multiple cross-reactive effects. Recently, we discovered a naphthyl salicyl acyl hydrazone-based inhibitor (NSAH or E-3a) of human RR (hRR) binding at the catalytic site (C-site) and inhibiting hRR reversibly. We herein report the synthesis and biochemical characterization of 25 distinct analogs. We designed each analog through docking to the C-site of hRR based on our 2.7 ? X-ray crystal structure (PDB ID: 5TUS). Broad tolerance to minor structural variations preserving inhibitory potency is observed. E-3f (82% yield) displayed an in vitro IC50 of 5.3 ± 1.8 μM against hRR, making it the most potent in this series. Kinetic assays reveal that E-3a, E-3c, E-3t, and E-3w bind and inhibit hRR through a reversible and competitive mode. Target selectivity toward the R1 subunit of hRR is established, providing a novel way of inhibition of this crucial enzyme.
Rhodium-Catalyzed Double Alkyl-Oxygen Bond Cleavage: An Alkyl Transfer Reaction from Bis/Tris(o-alkyloxyphenyl)phosphine to Aryl Acids
Zhou, Hui,Zhang, Jinlong,Yang, Huameng,Xia, Chungu,Jiang, Gaoxi
supporting information, p. 3406 - 3412 (2016/10/21)
An unprecedented rhodium-catalyzed selective cleavage of double alkyl-oxygen bonds of bis/tris(o-alkyloxyphenyl)phosphine has been realized, in which P atom functions as a directing group and simple aryl acids are the methyl group acceptor to provide methyl esters and a quaternary phosphonium salt. The preliminary mechanism was investigated via an 18O labeling experiment and stoichiometric reaction between a Rh-A crystal and an aromatic acid.
