6396-76-5Relevant articles and documents
Chromatography-Free Multicomponent Synthesis of Thioureas Enabled by Aqueous Solution of Elemental Sulfur
Németh, András Gy.,Szabó, Renáta,Domján, Attila,Keser?, Gy?rgy M.,ábrányi-Balogh, Péter
, p. 16 - 27 (2020/12/31)
The development of a new three-component chromatography-free reaction of isocyanides, amines and elemental sulfur allowed us the straightforward synthesis of thioureas in water. Considering a large pool of organic and inorganic bases, we first optimized the preparation of aqueous polysulfide solution from elemental sulfur. Using polysulfide solution, we were able to omit the otherwise mandatory chromatography, and to isolate the crystalline products directly from the reaction mixture by a simple filtration, retaining the sulfur in the solution phase. A wide range of thioureas synthesized in this way confirmed the reasonable substrate and functional group tolerance of our protocol.
Effect of N-1 arylation of monastrol on kinesin Eg5 inhibition in glioma cell lines
Gon?alves, Itamar Luís,Rockenbach, Liliana,Das Neves, Gustavo Machado,G?ethel, Gabriela,Nascimento, Fabiana,Porto Kagami, Luciano,Figueiró, Fabrício,Oliveira De Azambuja, Gabriel,De Fraga Dias, Amanda,Amaro, Andressa,De Souza, Lauro Mera,Da Rocha Pitta, Ivan,Avila, Daiana Silva,Kawano, Daniel Fábio,Garcia, Solange Cristina,Battastini, Ana Maria Oliveira,Eifler-Lima, Vera Lucia
, p. 995 - 1010 (2018/06/27)
An original and focused library of two sets of dihydropyrimidin-2-thiones (DHPMs) substituted with N-1 aryl groups derived from monastrol was designed and synthesized in order to discover a more effective Eg5 ligand than the template. Based on molecular docking studies, four ligands were selected to perform pharmacological investigations against two glioma cell lines. The results led to the discovery of two original compounds, called 20h and 20e, with an anti-proliferative effects, achieving IC50 values of about half that of the IC50 of monastrol in both cell lines. As with monastrol, flow cytometry analyses showed that the 20e and 20h compounds induced cell cycle arrest in the G2/M phase, and immunocytochemistry essays revealed the formation of monopolar spindles due to Eg5 inhibition without any toxicity to Caenorhabditis elegans.
A poised fragment library enables rapid synthetic expansion yielding the first reported inhibitors of PHIP(2), an atypical bromodomain
Cox, Oakley B.,Krojer, Tobias,Collins, Patrick,Monteiro, Octovia,Talon, Romain,Bradley, Anthony,Fedorov, Oleg,Amin, Jahangir,Marsden, Brian D.,Spencer, John,Von Delft, Frank,Brennan, Paul E.
, p. 2322 - 2330 (2016/03/05)
Research into the chemical biology of bromodomains has been driven by the development of acetyl-lysine mimetics. The ligands are typically anchored by binding to a highly conserved asparagine residue. Atypical bromodomains, for which the asparagine is mutated, have thus far proven elusive targets, including PHIP(2) whose parent protein, PHIP, has been linked to disease progression in diabetes and cancers. The PHIP(2) binding site contains a threonine in place of asparagine, and solution screening have yielded no convincing hits. We have overcome this hurdle by combining the sensitivity of X-ray crystallography, used as the primary fragment screen, with a strategy for rapid follow-up synthesis using a chemically-poised fragment library, which allows hits to be readily modified by parallel chemistry both peripherally and in the core. Our approach yielded the first reported hit compounds of PHIP(2) with measurable IC50 values by an AlphaScreen competition assay. The follow-up libraries of four poised fragment hits improved potency into the sub-mM range while showing good ligand efficiency and detailed structural data.
