4335-61-9Relevant academic research and scientific papers
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.
Convenient route to primary (Z)-allyl amines and homologs
Gerpe, Alejandra,Bollini, Mariela,Gonzalez, Mercedes,Cerecetto, Hugo
experimental part, p. 29 - 47 (2009/04/06)
A convenient two-step procedure for the synthesis of primary (Z)-allyl amines, (Z)-homoallyl amines [(Z)-but-3-enylamines], and (Z)-pent-4-enylamines using the Wittig reaction was achieved. The use of nonstabilized ylides from triphenylphosphonium salt, potassium salt, and apolar solvent produced (Z/E)-geometric isomer ratios generally greater than 1.6. The amine moiety was masked using a phtalimide group that was removed successfully in the last step of the process in two different conditions, NH2NH2/EtOH/rt or CH3NH2/EtOH/rt. However, in some cases, reduction of the C = C double bond in the deprotection with hydrazine was concomitantly observed. Copyright Taylor & Francis Group, LLC.
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
Phenyl substituted dipeptide amides
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, (2008/06/13)
The invention relates to novel substituted tyrosyl alanine dipeptide amides of the formula: STR1 and the pharmaceutically acceptable acid addition salts thereof wherein R1 is hydrogen, lower alkyl, hydroxy, --OCO2 lower alkyl, lower alkoxy, --O(CH2)n -phenyl with the phenyl optionally substituted by halogen, --NO2, --CN, --NH2 or lower alkyl wherein n is 1 to 4; R2 and R3 represent lower alkyl, halogen, or lower alkoxy, or either one of R2 or R3 is hydrogen and the other is lower alkyl, lower alkoxy or halogen; R4, R5, R6, R7, R8, and R9 may be the same or different and represent hydrogen or lower alkyl; R10 is selected from the group consisting of where ALK represents alkylene, thioalkylene, oxyalkylene, having 1 to 5 carbon atoms; alkenylene and alkynylene having 2 to 4 carbon atoms; and X represents pyridyl, pyrimidinyl, 9H-fluoren-9-yl, diphenylmethyl, thienyl, carboxy, lower alkoxy carbonyl, substituted phenyl wherein the phenyl substituent is amino, hydroxy, halogen, nitro, methylenedioxy, lower alkyl, carboxy, lower alkoxycarbonyl, lower alkoxy, carboxamide, diloweralkylamino or X represents phenyl, when ALK is not alkylene; or R10 is STR2 where p and q are independently 1 to 4; or R9 and R10 together with N is STR3 where r and t are independently 1 to 4; v represents an asymmetric carbon that may be racemic or have the D or L configuration; w represents an asymmetric carbon when R7 and R8 are not the same that may be racemic or have the D or L configuration. These compounds are useful as analgesic and/or antihypertensive compounds.
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
