97248-85-6Relevant articles and documents
Synthesis of 2,3-Bis[amino(benzylsulfanyl)methylidene]butanedinitrile and 2-(Benzylsulfanyl)pyridine-3-carbonitrile derivatives
Dyachenko,Dyachenko,Dorovatovskii,Khrustalev,Torocheshnikov,Nenajdenko
, p. 1785 - 1789 (2018)
The alkylation of cyanothioacetamide with benzyl chloride in DMF in the presence of 10% aqueous potassium hydroxide afforded 2,3-bis[amino(benzylsulfanyl)methylidene]butanedinitrile. Analogous reaction with addition of acetylacetone or its 3-methyl derivative led to the formation of 2-benzylsulfanyl-4,6-dimethylor -4,5,6-trimethylpyridine-3-carbonitrile.
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 of 4,6-dimethyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile by condensation of cyanothioacetamide with acetaldehyde and 1-(Prop-1-en-2-yl)piperidine
Dyachenko,Dyachenko
, p. 32 - 36 (2017/01/11)
Three-component condensation of cyanothioacetamide with acetaldehyde and 1-(prop-1-en-2-yl)-piperidine afforded 4,6-dimethyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile which was alkylated with alkyl halides to obtain substituted 2-alkylsulfanyl-4,6-dimethylpyridine-3-carbonitriles, (3-amino-4,6-dimethylthieno-[2,3-b]pyridin-2-yl)(4-cyclohexylphenyl)methanone, and 2,2′-[ethane-1,2-diylbis(sulfanediyl)]bis(4,6-dimethylpyridine-3-carbonitrile).
Functional sulfur-containing compounds : 1114. Study of intramolecular cyclization of 2-organylthio-, 2-organylsulfinyl-, and 2- organylsulfonylnicotinic acid esters and nitriles upon action of a base
Kalugin,Shestopalov
experimental part, p. 2139 - 2145 (2010/04/26)
The Thorpe-Ziegler intramolecular cyclization of 2-RCH2S-, 2-RCH2S(O)-, and 2-RCH2SO2-substituted nicotinic acid esters and nitriles (R is alkyl, aryl, and 2-thienyl) upon the action of potassium tert-butoxide has been studied. The reaction results in the formation of the corresponding 2-R-substituted 3-aminothieno[2,3-b]pyridines, 3-aminothieno[2,3-b]pyridine 1-oxides, and 3-aminothieno[2,3-b]pyridine 1,1-dioxides with the reaction taking place only in the case if R is aryl or 2-thienyl. Methyl esters of 2-RCH2S-, 2-RCH2S(O)-, and 2-RCH2SO2-substituted nicotinic acids also undergo the intramolecular cyclization of the Dieckmann type to form the corresponding 2-R-substituted 3-hydroxythieno[2,3-b]pyridines, thieno[2,3-b]pyridin-3(2H)-one 1-oxides, and thieno[2,3-b]pyridin-3(2H)-one 1,1-dioxides. Such a reaction takes place for all the R groups except when R = AlkCH2S and AlkCH 2S(O).
