Synthesis and pharmacological characterization of the selective GluK1 radioligand (S)-2-amino-3-(6-[³H]-2,4-dioxo-3,4-dihydrothieno[3,2-d]pyrimidin-1(2H)-yl)propanoic acid ([³H]-NF608)

Abstract

Expedite synthesis of [3H]NF608 – a new subtype selective GluK1 radioligand.

Frustrated Lewis pairs: A real alternative to deuteride/tritide reductions

“…To broaden the insights into the reactivity of 2 towards various carbonyl compounds, heteroaromates (9)(10)(11)(12)(13)(14) and isotopomers (4-6 and 11-13) were investigated ( Table 1, entries [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. The full conversion of substrates was achieved in all cases providing the appropriate labeled alcohol with 2 H-enrichment of over 95%.…”

“…Tritium, the most versatile radionuclide, readily labels small organic molecules of interest and is traditionally used in ligand-biological receptor-structure-activity studies or in administration, distribution, metabolism, and excretion (ADME) studies. 2,3,[10][11][12][13] The current status of tritium chemistry methodologies comprises out of a portfolio of few fundamental synthetic approaches that radiochemist can chose from: metalcatalyzed exchange (hydrogen isotope exchange [HIE]), [14][15][16][17][18][19][20][21] tritiodehalogenation, [22][23][24][25][26][27][28] multiple bond reduction 27,[29][30][31] with T 2 , and tritides reduction ( Figure 1). 22,23,[32][33][34] The quite inert molecule of hydrogen always needs to be activated before any intended application.…”

Crystal structure and Hirshfeld surface analysis of 3,6-bis(pyrimidin-2-yl)-1,4-dihydro-1,2,4,5-tetrazine dihydrate

“…The chemistry of nitrogen-containing heterocyclic compounds has attracted the attention of the scientific community for over a century. Many compounds of this class are bioactive (Jubeen et al, 2018) and show promising pharmacological properties (Alcaide et al, 2016;Varano et al, 2016). Among these, numerous pyrimidine derivatives have been studied extensively in the context of synthetic organic chemistry and coordination chemistry (Kaim, 2002).…”

Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor Antagonist

“…40 Ligand affinities at recombinant homomeric rat GluK1-3 were determined using [ 3 H]KA as the radioligand as previously detailed (Sagot et al, 2008; Alcaide et al, 2016). 41,42 Data were analyzed using GraphPad Prism 7 (GraphPad Software, San Diego, CA) do determine ligand IC 50 and K i values.…”