72456-86-1Relevant articles and documents
2-Sulfonylpyridines as Tunable, Cysteine-Reactive Electrophiles
Zambaldo, Claudio,Vinogradova, Ekaterina V.,Qi, Xiaotian,Iaconelli, Jonathan,Suciu, Radu M.,Koh, Minseob,Senkane, Kristine,Chadwick, Stormi R.,Sanchez, Brittany B.,Chen, Jason S.,Chatterjee, Arnab K.,Liu, Peng,Schultz, Peter G.,Cravatt, Benjamin F.,Bollong, Michael J.
supporting information, p. 8972 - 8979 (2020/12/23)
The emerging use of covalent ligands as chemical probes and drugs would benefit from an expanded repertoire of cysteine-reactive electrophiles for efficient and diverse targeting of the proteome. Here we use the endogenous electrophile sensor of mammalian cells, the KEAP1-NRF2 pathway, to discover cysteine-reactive electrophilic fragments from a reporter-based screen for NRF2 activation. This strategy identified a series of 2-sulfonylpyridines that selectively react with biological thiols via nucleophilic aromatic substitution (SNAr). By tuning the electrophilicity and appended recognition elements, we demonstrate the potential of the 2-sulfonylpyridine reactive group with the discovery of a selective covalent modifier of adenosine deaminase (ADA). Targeting a cysteine distal to the active site, this molecule attenuates the enzymatic activity of ADA and inhibits proliferation of lymphocytic cells. This study introduces a modular and tunable SNAr-based reactive group for targeting reactive cysteines in the human proteome and illustrates the pharmacological utility of this electrophilic series.
Synthesis and antitumor evaluation of some new fused and binary pyridines
Waly, Mohamed A.,El-Hawary, Ibrahim I.,Hamama, Wafaa S.,Zoorob, Hanafi H.
, p. E12-E17 (2013/06/04)
Syntheses of some new heterocyclic compounds containing pyridone, thioxopyridine, halogenated-pyridine-carbonitriles, pyrazolopyridine, and pyridine derivatives were achieved. Besides, a modified synthetic method for the synthesis of 2-chloro-4,6-dimethyl-nicotinonitrile () through the reaction of acetylacetone and malononitrile as starting materials was implemented. The reaction of 2-chloronicotinonitrile with substituted amines to 2-aminonicotinonitrile were also investigated. Fused or binary pyridines were tested for cytotoxicity against well-known established model Ehrlich ascites cells in vitro. Compound exhibited a high antitumor activity compared with 5-fluorouracil.
Heteroaromatic thioether-boronic acid cross-coupling under neutral reaction conditions.
Liebeskind, Lanny S,Srogl, Jiri
, p. 979 - 981 (2007/10/03)
[reaction: see text] Pi-deficient heteroaromatic thioethers undergo efficient palladium-catalyzed cross-coupling with boronic acids mediated by copper(I) thiophene-2-carboxylate.
