One stage synthesis of 4,6-diaryl-3-cyanopyridine-2(1H)-thiones

High-Throughput Screening and Hit Validation of Extracellular-Related Kinase 5 (ERK5) Inhibitors

“…10 In hepatocellular carcinoma (HCC), ERK5 overexpression has been reported, associated with gene amplification at the 17p11 chromosome fragment, harboring the MAPK7 gene. 11 High levels of ERK5 were found to correlate with more aggressive and metastatic stages in fresh samples from human clear cell renal cell carcinoma. 12 To date, three small-molecule inhibitors of the MEK5/ERK5 pathway have been described.…”

“…The residue was triturated with petrol until a solid formed, then filtered, washing with 1M HCl (25 mL). 11 A mixture of (E)-3-(4-fluorophenyl)-1-phenylprop-2-en-1-one (13a) A mixture of the required chalcone (1.0 eq. ), malononitrile (1.0 eq.…”

“…The first synthetic approach considered for the synthesis of 3-cyanopyridines was based on the route reported by Shestopalov et al For example, 4-fluorochalcone 13a , prepared via Claisen–Schmidt condensation of acetophenone with 4-fluorobenzaldehyde, was treated with elemental sulfur and morpholine in ethanol at reflux, followed by malononitrile, to give pyridinethione 14a in moderate yield (Method A, Scheme ). Isolation of the intermediate pyridinethiones 14 required extensive purification, attributed to the propensity of this intermediate to tautomerise, and its readiness to oxidize under atmospheric conditions.…”

Multicomponent Reactions of Carbonyl Compounds and Derivatives of Cyanoacetic Acid: Synthesis of Carbo- and Heterocycles

“…143 Notably, the multicomponent transformation of unsaturated ketones 183, malononitrile, and elemental sulfur is the only reaction known to produce 4,6-disubstituted 3-cyanopyridine-2(1H)-thiones 194 in high yields (84-96%) without utilizing hydrogen sulfide (Scheme 52, Table 9). 72,127,146 Most likely, compounds 194 are formed stepwise through Michael adducts 191, a-mercaptoketones 192, and iminothiiranes 193. To some extent, the proposed reaction scheme was confirmed by introducing Michael adducts into this synthesis; these Michael adducts had previously been used as starting reagents for the preparation of pyridine-2(1H)-thiones 194.…”

Synthesis, Reactions and Characterization of 1,1’-(1,4-Phenylenebis(3-amino-6-methyl-1H-pyrazolo[3,4-b]pyridine-4,5-diyl))bis(ethan-1-one)

“…Also, bis-compounds have received great attention [9] [10] not only for being model compounds for main chain polymers [11]- [16] but also because many biologically active natural and synthetic products have molecular symmetry [17]. The biological importance of both bis-compounds [18]- [21] and 2-thioxopyridine-3-carbonitriles [22]- [24] as well as the conjunction to our previous work [25]- [33] stimulated our interest to synthesize several derivatives of these ring systems that are required for several chemical transformations and medicinal chemistry programs.…”