42970-79-6Relevant articles and documents
New uncharged 2-thienostilbene oximes as reactivators of organophosphate-inhibited cholinesterases
?ade?, Tena,?kori?, Irena,Bari?, Danijela,Kovarik, Zrinka,Lasi?, Kornelija,Marini?, ?eljko,Mlaki?, Milena,Pu?ek, Ivana,Ratkovi?, Ana
, (2021/11/27)
The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by organophosphates (OPs) as nerve agents and pesticides compromises normal cholinergic nerve signal transduction in the peripheral and central nervous systems (CNS) leading to cholinergic crisis. The treatment comprises an antimuscarinic drug and an oxime reactivator of the inhibited enzyme. Oximes in use have quaternary nitrogens, and therefore poorly cross the brain–blood barrier. In this work, we synthesized novel uncharged thienostilbene oximes by the Wittig reaction, converted to aldehydes by Vilsmeier formylation, and transformed to the corresponding uncharged oximes in very high yields. Eight trans,anti-and trans,syn-isomers of oximes were tested as reactivators of nerve-agent-inhibited AChE and BChE. Four derivatives reactivated cyclosarin-inhibited BChE up to 70% in two hours of reactivation, and docking studies confirmed their productive interactions with the active site of cyclosarin-inhibited BChE. Based on the moderate binding affinity of both AChE and BChE for all selected oximes, and in silico evaluated ADME properties regarding lipophilicity and CNS activity, these compounds present a new class of oximes with the potential for further development of CNS-active therapeutics in OP poisoning.
Model Guided Development of a Simple Catalytic Method for the Synthesis of Unsymmetrical Stilbenes by Sequential Heck Reactions of Aryl Bromides with Ethylene
Barlow, Helen,Buser, Jonas Y.,Glauninger, Hendrik,Luciani, Carla V.,Martinelli, Joseph R.,Oram, Niall,Thompson-Van Hook, Nichole,Richardson, Jeffery
supporting information, p. 2678 - 2690 (2018/06/04)
Stilbenes are important and useful structural moieties, but methods for their preparation typically possess numerous inefficiencies. Presented here is a methodology for the two-step, one pot preparation of unsymmetrical stilbenes via sequential Heck reactions. The first Heck reaction with ethylene gas was analysed as a function of temperature and pressure for electronically differentiated naphthyl bromides and model-aided reaction optimization was utilized to define the system. In addition, reactNMR was utilized to determine ethylene solubility in common organic solvents useful for Heck reactions. Finally, an optimized sequential Heck reaction process was developed and applied to a range of substrates allowing for efficient preparation of unsymmetrical stilbenes, including the natural antioxidant, pterostilbene. (Figure presented.).
Determining the excited-state substituent constants of furyl and thienyl groups
Qu, Junyan,Cao, Chao-Tun,Cao, Chenzhong
supporting information, (2018/04/24)
Six series of styrene derivatives XCH═CHArY (total of 65) containing the styrene parent molecular skeleton were synthesized (here, Y is OMe, Me, H, F, Cl, CF3, CN, and NO2, and X is 2-furyl, 3-furyl, 2′-methyl-2-furyl, 2-thienyl, 3-thienyl, and 2′-methyl-2-theniyl). Their ultraviolet absorption spectra were measured in anhydrous ethanol, and their wavelength of absorption maximum λmax was recorded. For the wavenumber νmax (cm?1, νmax?=?1/λmax) of the obtained λmax, a quantitative correlation analysis was performed, and 6 excited-state substituent constants σexcc(p) of groups X were obtained by means of curve-fitting method. Taking the νmax values of total 90 compounds of styrene derivatives as a data set (including 25 compounds from reference and 65 compounds of this work), a quantitative correlation analysis was performed, and the reliability of the obtained σexcc(p) was verified. In addition, 12 samples of disubstituted Schiff bases (XCH═NArY) involving the above groups X were synthesized, and their νmax values were recorded. Using these 12 νmax together with the 14 νmax values of Schiff bases taken from reference (total of 26 compounds), it was further verified that the σexcc(p) values are reliable by means of quantitative correlation method.
