167023-89-4Relevant articles and documents
Structure–activity relationships of GPX4 inhibitor warheads
Cai, Luke L.,Eaton, John K.,Furst, Laura,Schreiber, Stuart L.,Viswanathan, Vasanthi S.
, (2020)
Direct inhibition of GPX4 requires covalent modification of the active-site selenocysteine. While phenotypic screening has revealed that activated alkyl chlorides and masked nitrile oxides can inhibit GPX4 covalently, a systematic assessment of potential electrophilic warheads with the capacity to inhibit cellular GPX4 has been lacking. Here, we survey more than 25 electrophilic warheads across several distinct GPX4-targeting scaffolds. We find that electrophiles with attenuated reactivity compared to chloroacetamides are unable to inhibit GPX4 despite the expected nucleophilicity of the selenocysteine residue. However, highly reactive propiolamides we uncover in this study can substitute for chloroacetamide and nitroisoxazole warheads in GPX4 inhibitors. Our observations suggest that electrophile masking strategies, including those we describe for propiolamide- and nitrile-oxide-based warheads, may be promising for the development of improved covalent GPX4 inhibitors.
Flow synthesis of secondary amines over Ag/Al2O3 catalyst by one-pot reductive amination of aldehydes with nitroarenes
Artiukha, Ekaterina A.,Nuzhdin, Alexey L.,Bukhtiyarova, Galina A.,Bukhtiyarov, Valerii I.
, p. 45856 - 45861 (2017/10/06)
An alumina-supported silver catalyst was investigated in the one-pot reductive amination of aldehydes with nitroarenes in a continuous flow reactor using molecular hydrogen as a reducing agent. A series of secondary amines containing alkyl, OH, OCH3, Cl, Br and CC groups was synthesized in good to excellent yields. The yield of the secondary amine depends on the rate of formation of an intermediate imine. It was shown that the accumulation of carbonaceous deposits on the catalyst is the main reason of catalyst deactivation. The spent catalyst can be easily regenerated and reused without losing catalytic activity.
