151621-88-4Relevant articles and documents
Development of Bisindole-Substituted Aminopyrazoles as Novel GSK-3β Inhibitors with Suppressive Effects against Microglial Inflammation and Oxidative Neurotoxicity
Liu, Jian-Guo,Zhao, Danfeng,Gong, Qi,Bao, Fengxia,Chen, Wen-Wen,Zhang, Haiyan,Xu, Ming-Hua
, p. 3398 - 3408 (2020)
Development of glycogen synthase kinase-3β (GSK-3β) inactivation-centric agents with polypharmacological profiles is increasingly recognized as a promising therapeutic strategy against the multifactorial etiopathology of Alzheimer's disease (AD). In this respect, a series of disubstituted aminopyrazole derivatives were designed and synthesized as a new class of GSK-3β inhibitors. Most of these derivatives possess GSK-3β inhibitory activities with IC50 values in the micromolar ranges, among which bisindole-substituted aminopyrazole derivative 6h displayed moderate GSK-3β inhibition (IC50 = 1.76 ± 0.19 μM), and alleviative effects against lipopolysaccharide (LPS)-induced glial inflammation in BV-2 cells and glutamate-induced oxidative neurotoxicity in HT-22 cells. Further in vivo studies indicated that compound 6h had potent anti-inflammatory effect, by showing markedly reduced microglial activation and astrocyte proliferation in the brain of LPS-injected mice. Overall, the simultaneous modulation of 6h on multiple dysfunctions of disease network highlights this structural distinctively bisindole-substituted aminopyrazole could be a useful prototype for the discovery of novel therapeutic agents to tackle AD and other GSK-3β associated complex neurological syndromes.
Grignard-mediated reduction of 2,2,2-trichloro-1-arylethanones
Essa, Ali H.,Lerrick, Reinner I.,?ift?i, E?e,Harrington, Ross W.,Waddell, Paul G.,Clegg, William,Hall, Michael J.
supporting information, p. 5793 - 5803 (2015/05/27)
2,2,2-Trichloro-1-aryl-ethanones can be reduced by RMgX to the corresponding 2,2-dichloro-1-arylethen-1-olates and trapped with a range of electrophiles resulting in either reduction, reduction/aldol, reduction/Claisen condensation or reduction/aldol-Tishchenko products. In addition we demonstrate that 2,2-dichloro-1-arylethen-1-olates undergo counter-ion controlled Darzens condensations, which can be followed by a thermal rearrangement as a route to 1,3-diaryl-3-chloropropane-1,2-diones.
