1678-25-7Relevant articles and documents
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Rogne
, p. 1855 (1971)
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Metal-Free Mediated Meerwein-Type Reaction: A Radical Cascade Arylation/Aryl Migration/Desulfonylation of Conjugated Alkenes
Ni, Zhangqin,Huang, Xin,Pan, Yuanjiang
, p. 2612 - 2615 (2016)
A metal-free cascade arylation/aryl migration/desulfonylation of N-phenyl-N-(phenylsulfonyl)methacrylamide is described. The in situ generated diazonium salts from anilines and t-BuONO are used as aryl precursors. This process provides an efficient strategy for the synthesis of α-all-carbon quaternary stereocenters amides. A radical mechanism was proposed for this transformation.
Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds
Pallesen, Jakob S.,Narayanan, Dilip,Tran, Kim T.,Solbak, Sara M. ?.,Marseglia, Giuseppe,S?rensen, Louis M. E.,H?j, Lars J.,Munafò, Federico,Carmona, Rosa M. C.,Garcia, Anthony D.,Desu, Haritha L.,Brambilla, Roberta,Johansen, Tommy N.,Popowicz, Grzegorz M.,Sattler, Michael,Gajhede, Michael,Bach, Anders
, p. 4623 - 4661 (2021/05/07)
Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.
Copper-Catalyzed Aminoarylation of Alkenes via Aminyl Radical Addition and Aryl Migration
Liu, Mei-Ling,Liu, Xue-Yuan,Sun, Wen-Hui,Wang, Jin-Lin,Zou, Jian-Yu
supporting information, (2022/01/04)
We describe a new strategy for aminoarylation of alkenes by copper-catalyzed smiles rearrangement using O-benzoylhydroxylamines as the amine reagent. This method affords various β-amino amide derivatives possessing a quaternary carbon center with wide functional group tolerance and high regioselectivity. The mechanistic studies indicate that the transformation can involve aminyl radical intermediates under acid-free condition.
