FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2072510182> ?p ?o ?g. }

• W2072510182 endingPage "7829" @default.
• W2072510182 startingPage "7816" @default.
• W2072510182 abstract "The interaction of tropomyosin-related kinase B (TrkB) with the cognate ligand brain-derived neurotrophic factor (BDNF) mediates fundamental pathways in the development of the nervous system. TrkB signaling alterations are linked to numerous neurodegenerative diseases and conditions. Herein we report the synthesis, biological evaluation and radiosynthesis of the first TrkB radioligands based on the recently identified 7,8-dihydroxyflavone chemotype. 2-(4-[(18)F]fluorophenyl)-7,8-dihydroxy-4H-chromen-4-one ([(18)F]10b) was synthesized in high radiochemical yields via an efficient SNAr radiofluorination involving a para-Michael acceptor substituted aryl followed by BBr3-promoted double demethylation. Selective N-[(11)C]methylation afforded 2-(4-([N-methyl-(11)C]-dimethylamino)phenyl)-7,8-dihydroxy-4H-chromen-4-one ([(11)C]10c) from the fully deprotected catechol-bearing normethyl precursor 13 with [(11)C]MeOTf. In vitro autoradiography of [(18)F]10b with transverse rat brain sections revealed high specific binding in the cortex, striatum, hippocampus and thalamus in accordance with expected TrkB distribution. Blockade experiments with both 7,8-dihydroxyflavone (1a) and TrkB cognate ligand, BDNF, led to decreases of 80% and 85% of radioligand binding strongly supporting the hypothesis that 7,8-dihydroxyflavones exert their effect on TrkB phosphorylation via direct TrkB extracellular domain (ECD) binding. Positron emission tomography (PET) studies revealed that [(18)F]10b and [(11)C]10c brain uptake is minimal and that they are rapidly eliminated from the plasma (effective plasma half-life 5-10 min) via hepatic secretion. Nevertheless, the high specific binding and TrkB specificity derived from in vitro experiments suggests that the 7,8-disubstituted flavone chemotype represents a promising scaffold for the development of TrkB radiotracers for PET." @default.
• W2072510182 created "2016-06-24" @default.
• W2072510182 creator A5046857550 @default.
• W2072510182 creator A5052647484 @default.
• W2072510182 creator A5060556757 @default.
• W2072510182 creator A5085283815 @default.
• W2072510182 creator A5091097481 @default.
• W2072510182 date "2013-12-01" @default.
• W2072510182 modified "2023-09-23" @default.
• W2072510182 title "Towards tropomyosin-related kinase B (TrkB) receptor ligands for brain imaging with PET: Radiosynthesis and evaluation of 2-(4-[18F]fluorophenyl)-7,8-dihydroxy-4H-chromen-4-one and 2-(4-([N-methyl-11C]-dimethylamino)phenyl)-7,8-dihydroxy-4H-chromen-4-one" @default.
• W2072510182 cites W136988321 @default.
• W2072510182 cites W1596784725 @default.
• W2072510182 cites W1602778375 @default.
• W2072510182 cites W1966507933 @default.
• W2072510182 cites W1967838513 @default.
• W2072510182 cites W1971729859 @default.
• W2072510182 cites W1979702721 @default.
• W2072510182 cites W1980255753 @default.
• W2072510182 cites W1984799198 @default.
• W2072510182 cites W1985822867 @default.
• W2072510182 cites W1986711579 @default.
• W2072510182 cites W1999154321 @default.
• W2072510182 cites W2000637724 @default.
• W2072510182 cites W2003338094 @default.
• W2072510182 cites W2005235959 @default.
• W2072510182 cites W2006733352 @default.
• W2072510182 cites W2007458784 @default.
• W2072510182 cites W2007612721 @default.
• W2072510182 cites W2009046676 @default.
• W2072510182 cites W2010825793 @default.
• W2072510182 cites W2011204935 @default.
• W2072510182 cites W2012423618 @default.
• W2072510182 cites W2027843873 @default.
• W2072510182 cites W2032163025 @default.
• W2072510182 cites W2032781690 @default.
• W2072510182 cites W2033180168 @default.
• W2072510182 cites W2033356866 @default.
• W2072510182 cites W2033531253 @default.
• W2072510182 cites W2042905219 @default.
• W2072510182 cites W2050120720 @default.
• W2072510182 cites W2055583081 @default.
• W2072510182 cites W2063849763 @default.
• W2072510182 cites W2064865731 @default.
• W2072510182 cites W2069462123 @default.
• W2072510182 cites W2080985284 @default.
• W2072510182 cites W2083657788 @default.
• W2072510182 cites W2084478052 @default.
• W2072510182 cites W2084771891 @default.
• W2072510182 cites W2087102666 @default.
• W2072510182 cites W2088754913 @default.
• W2072510182 cites W2091927578 @default.
• W2072510182 cites W2104320396 @default.
• W2072510182 cites W2106620733 @default.
• W2072510182 cites W2109008714 @default.
• W2072510182 cites W2109169089 @default.
• W2072510182 cites W2109820768 @default.
• W2072510182 cites W2112459088 @default.
• W2072510182 cites W2133151521 @default.
• W2072510182 cites W2133228174 @default.
• W2072510182 cites W2139565721 @default.
• W2072510182 cites W2142181595 @default.
• W2072510182 cites W2143834680 @default.
• W2072510182 cites W2143935514 @default.
• W2072510182 cites W2168152872 @default.
• W2072510182 cites W2951240671 @default.
• W2072510182 doi "https://doi.org/10.1016/j.bmc.2013.10.012" @default.
• W2072510182 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24183588" @default.
• W2072510182 hasPublicationYear "2013" @default.
• W2072510182 type Work @default.
• W2072510182 sameAs 2072510182 @default.
• W2072510182 citedByCount "19" @default.
• W2072510182 countsByYear W20725101822014 @default.
• W2072510182 countsByYear W20725101822015 @default.
• W2072510182 countsByYear W20725101822017 @default.
• W2072510182 countsByYear W20725101822018 @default.
• W2072510182 countsByYear W20725101822019 @default.
• W2072510182 countsByYear W20725101822020 @default.
• W2072510182 countsByYear W20725101822021 @default.
• W2072510182 crossrefType "journal-article" @default.
• W2072510182 hasAuthorship W2072510182A5046857550 @default.
• W2072510182 hasAuthorship W2072510182A5052647484 @default.
• W2072510182 hasAuthorship W2072510182A5060556757 @default.
• W2072510182 hasAuthorship W2072510182A5085283815 @default.
• W2072510182 hasAuthorship W2072510182A5091097481 @default.
• W2072510182 hasConcept C116569031 @default.
• W2072510182 hasConcept C15744967 @default.
• W2072510182 hasConcept C160539049 @default.
• W2072510182 hasConcept C169760540 @default.
• W2072510182 hasConcept C170493617 @default.
• W2072510182 hasConcept C185592680 @default.
• W2072510182 hasConcept C2775842073 @default.
• W2072510182 hasConcept C2776970183 @default.
• W2072510182 hasConcept C2778790584 @default.
• W2072510182 hasConcept C55493867 @default.
• W2072510182 hasConcept C67847695 @default.
• W2072510182 hasConcept C71240020 @default.
• W2072510182 hasConcept C97124661 @default.
• W2072510182 hasConceptScore W2072510182C116569031 @default.

• next