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.
Substituent Dependent Optical Properties of p-phenyl Substituted ethenyl-E-thiophenes
Kumar, Naresh,Paramasivam, Mahalingavelar,Kumar, Jagdeep,Gusain, Anamika,Hota, Prasanta Kumar
, p. 1207 - 1216 (2018/09/10)
Various electron donor and acceptor substituted (NO2, CN, Cl, H, OCH3, NH2) p-phenyl ethenyl-E- thiophenes (1–6) were synthesized and substituent dependent optical properties (dipole moment, transition dipole moment, oscillator strength, optical band gap, hyperpolarizability) were studied using Solvatochromism and Density functional theory. It is shown that thiophene acts as a weak electron donor in presence of an electron withdrawing p-phenyl substituent (NO2, CN, Cl), whereas thiophene acts as a weak electron acceptor in presence of an electron donating p-phenyl substituent (OCH3, NH2). In comparison to ethenyl thiophene 4, the HOMO-LUMO energy band gap is decreased upon increasing the electron donating or electron withdrawing capacity of p-phenyl substituent. From the excited state dipole moment calculation, it is shown that the excited state is highly dipolar for nitro and amino compounds 1 and 6, whereas compounds 2–5 show a non-polar excited state. As compared to the ethenyl thiophene 4, the first hyperpolarizability (β) increases upon substitution either with a strong electron withdrawing or strong electron donating p-phenyl substituent. A large β value is found for p-nitro phenyl ethenyl-E-thiophene and p-amino phenyl ethenyl-E- thiophene. Overall, these studies provide useful information in understanding the optical properties of phenyl and heterocyclic based ethenyl systems.
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.).
