Moldovan, RP; Wenzel, B; Teodoro, R; Neumann, W; Dukic-Stefanovic, S; Kraus, W; Rong, PJ; Deuther-Conrad, W; Hey-Hawkins, E; Krugel, U; Brust, P in [Moldovan, Rares-Petru; Wenzel, Barbara; Teodoro, Rodrigo; Dukic-Stefanovic, Sladjana; Deuther-Conrad, Winnie; Brust, Peter] Helmholtz Zentrum Dresden Rossendorf, Inst Radiopharmaceut Canc Res, Permoserstr 15, D-04318 Leipzig, Germany; [Kraus, Werner] BAM Fed Inst Mat Res & Testing, Richard Willstatter Str 11, D-12489 Berlin, Germany; [Neumann, Wilma; Hey-Hawkins, Evamarie] Univ Leipzig, Fac Chem & Mineral, Inst Inorgan Chem, D-04103 Leipzig, Germany; [Kruegel, Ute] Univ Leipzig, Fac Med, Rudolf Boehm Inst Pharmacol & Toxicol, D-04107 Leipzig, Germany; [Rong, Peijing] China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing 100700, Peoples R China published Studies towards the development of a PET radiotracer for imaging of the P2Y(1) receptors in the brain: synthesis, F-18-labeling and preliminary biological evaluation in 2019.0, Cited 67.0. HPLC of Formula: C8H11NO. The Name is 2-(4-Aminophenyl)ethanol. Through research, I have a further understanding and discovery of 104-10-9.
Purine nucleotides such as ATP and ADP are important extracellular signaling molecules in almost all tissues activating various subtypes of purinoreceptors. In the brain, the P2Y(1) receptor (P2Y(1)R) subtype mediates trophic functions like differentiation and proliferation, and modulates fast synaptic transmission, both suggested to be affected in diseases of the central nervous system. Research on P2Y(1)R is limited because suitable brain-penetrating P2Y(1)R-selective tracers are not yet available. Here, we describe the first efforts to develop an F-18-labeled PET tracer based on the structure of the highly affine and selective, non-nucleotidic P2Y(1)R allosteric modulator 1-(2-[2-(tert-butyl)phenoxy]pyridin-3-yl)-3-[4- (trifluoromethoxy)phenyl]urea (7). A small series of fluorinated compounds was developed by systematic modification of the p-(trifluoromethoxy)phenyl, the urea and the 2-pyridyl subunits of the lead compound 7. Additionally, the p-(trifluoromethoxy)phenyl subunit was substituted by carborane, a boron-rich cluster with potential applicability in boron neutron capture therapy (BNCT). By functional assays, the new fluorinated derivative 1-{2-[2-(tert-butyl)phenoxy]pyridin-3-yl}-3-[4-(2-fluoroethyl) phenyl]urea (18) was identified with a high P2Y(1)R antagonistic potency (IC50 = 10 nM). Compound [F-18] 18 was radiosynthesized by using tetra-n-butyl ammonium [F-18]fluoride with high radiochemical purity, radiochemical yield and molar activities. Investigation of brain homogenates using hydrophilic interaction chromatography (HILIC) revealed [F-18]fluoride as major radiometabolite. Although [F-18]18 showed fast in vivo metabolization, the high potency and unique allosteric binding mode makes this class of compounds interesting for further optimizations and investigation of the theranostic potential as PET tracer and BNCT agent. (C) 2019 Elsevier Masson SAS. All rights reserved.
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