3749-51-7Relevant articles and documents
Structural and electronic modifications of pyridones and pyrones via regioselective bromination and trifluoromethylation
Seo, Junhyeok,Sotman, Timothy E.,Sullivan, Eileen R.,Ellis, Bryan D.,Phung, Truc,Rose, Michael J.
, p. 4519 - 4528 (2017)
We report regioselective functionalization of pyridones and pyrones via electrophilic bromination (Br2) or radical trifluoromethylation (NaSO2CF3/tBuOOH) at the 3-position. Counter-intuitively, the 3-position EW groups decreased the carbonyl stretching energy by 6–23 cm?1; however, 3,5-dibromination increased the C[dbnd]O frequency by 10–22 cm?1 compared to the 3-Br pyridones. X-ray crystallography revealed pyridone tautomers with contracted C[dbnd]O bond metrics. pKa values and 1H NMR shifts for the series 3-H→Br→CF3 revealed the expected trend of increasing acidity (pKa = 8.85 → 8.33→6.78, MeOH) and increasing chemical shifts (10.97 → 11.42→11.71 DMSO-d6). We conclude that the paradoxical decrease in CO stretching frequencies by the 3-positoin EW groups is explained by an ‘assistive’ electron-withdrawing effect, whereby the 3-position EW group assists the electronegative oxygen atom in recruiting more electron density, and – as a result – attaining more oxyanion character (decreased the C[dbnd]O bond strength).
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Collie,Myers
, (1892)
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COUMARIN-LIKE CYCLIC COMPOUND AS MEK INHIBITOR AND USE THEREOF
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Paragraph 0219-0221, (2020/05/30)
Disclosed are a class of coumarin-like cyclic compounds as MEK inhibitors and pharmaceutical compositions comprising the compounds, and the use of same in the preparation of a drug for treating MEK-related diseases. Particularly disclosed are compounds as shown in formula (I) and pharmaceutically acceptable salts thereof or tautomers thereof.
Small molecule inhibitors of anthrax edema factor
Jiao, Guan-Sheng,Kim, Seongjin,Moayeri, Mahtab,Thai, April,Cregar-Hernandez, Lynne,McKasson, Linda,O'Malley, Sean,Leppla, Stephen H.,Johnson, Alan T.
supporting information, p. 134 - 139 (2017/12/06)
Anthrax is a highly lethal disease caused by the Gram-(+) bacteria Bacillus anthracis. Edema toxin (ET) is a major contributor to the pathogenesis of disease in humans exposed to B. anthracis. ET is a bipartite toxin composed of two proteins secreted by the vegetative bacteria, edema factor (EF) and protective antigen (PA). Our work towards identifying a small molecule inhibitor of anthrax edema factor is the subject of this letter. First we demonstrate that the small molecule probe 5′-Fluorosulfonylbenzoyl 5′-adenosine (FSBA) reacts irreversibly with EF and blocks enzymatic activity. We then show that the adenosine portion of FSBA can be replaced to provide more drug-like molecules which are up to 1000-fold more potent against EF relative to FSBA, display low cross reactivity when tested against a panel of kinases, and are nanomolar inhibitors of EF in a cell-based assay of cAMP production.