4335-61-9Relevant articles and documents
Structural Basis for Achieving GSK-3β Inhibition with High Potency, Selectivity, and Brain Exposure for Positron Emission Tomography Imaging and Drug Discovery
Bernard-Gauthier, Vadim,Mossine, Andrew V.,Knight, Ashley,Patnaik, Debasis,Zhao, Wen-Ning,Cheng, Chialin,Krishnan, Hema S.,Xuan, Lucius L.,Chindavong, Peter S.,Reis, Surya A.,Chen, Jinshan Michael,Shao, Xia,Stauff, Jenelle,Arteaga, Janna,Sherman, Phillip,Salem, Nicolas,Bonsall, David,Amaral, Brenda,Varlow, Cassis,Wells, Lisa,Martarello, Laurent,Patel, Shil,Liang, Steven H.,Kurumbail, Ravi G.,Haggarty, Stephen J.,Scott, Peter J. H.,Vasdev, Neil
, p. 9600 - 9617 (2019/10/28)
Using structure-guided design, several cell based assays, and microdosed positron emission tomography (PET) imaging, we identified a series of highly potent, selective, and brain-penetrant oxazole-4-carboxamide-based inhibitors of glycogen synthase kinase-3 (GSK-3). An isotopologue of our first-generation lead, [3H]PF-367, demonstrates selective and specific target engagement in vitro, irrespective of the activation state. We discovered substantial ubiquitous GSK-3-specific radioligand binding in Tg2576 Alzheimer's disease (AD), suggesting application for these compounds in AD diagnosis and identified [11C]OCM-44 as our lead GSK-3 radiotracer, with optimized brain uptake by PET imaging in nonhuman primates. GSK-3β-isozyme selectivity was assessed to reveal OCM-51, the most potent (IC50 = 0.030 nM) and selective (>10-fold GSK-3β/GSK-3α) GSK-3β inhibitor known to date. Inhibition of CRMP2T514 and tau phosphorylation, as well as favorable therapeutic window against WNT/β-catenin signaling activation, was observed in cells.
Synthesis of heteroarenes using cascade radical cyclisation via iminyl radicals
Bowman, W. Russell,Cloonan, Martin O.,Fletcher, Anthony J.,Stein, Tobias
, p. 1460 - 1467 (2007/10/03)
Cascade radical cyclisation involving homolytic aromatic substitution has been used to synthesise new tetracycles. Treatment of vinyl iodide radical precursors with Me3Sn radicals (from hexamethylditin) yielded intermediate vinyl radicals which
Photochemistry of N-(2-Alkenyl)phthalimides. Photoinduced Cyclization and Elimination Reactions
Maruyama, Kazuhiro,Kubo, Yasuo
, p. 3612 - 3622 (2007/10/02)
The photochemical reactions of N-(2-alkenyl)phthalimides 4a-f were examined.Irradiation of a solution of 4a,b,d,f in methanol yielded a mixture of the methanol-incorporated cyclization products 5a + 6a, 13a-d, 15a + 16a, and 23 + 24, respectively.Chemical
