The Absolute Best Science Experiment for 1228185-09-8

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The preparation of ester heterocycles mostly uses heteroatoms as nucleophilic sites, which are achieved by intramolecular substitution or addition reactions. Compound: 2-Chloro-1,3-bis(2,6-diisopropylphenyl)-1H-imidazol-3-ium chloride( cas:1228185-09-8 ) is researched.Electric Literature of C27H36Cl2N2.Strebl, Martin G.; Campbell, Arthur J.; Zhao, Wen-Ning; Schroeder, Frederick A.; Riley, Misha M.; Chindavong, Peter S.; Morin, Thomas M.; Haggarty, Stephen J.; Wagner, Florence F.; Ritter, Tobias; Hooker, Jacob M. published the article 《HDAC6 Brain Mapping with [18F]Bavarostat Enabled by a Ru-Mediated Deoxyfluorination》 about this compound( cas:1228185-09-8 ) in ACS Central Science. Keywords: HDAC6 brain mapping imaging fluorine 18 bavarostat. Let’s learn more about this compound (cas:1228185-09-8).

Histone deacetylase 6 (HDAC6) function and dysregulation have been implicated in the etiol. of certain cancers and more recently in central nervous system (CNS) disorders including Rett syndrome, Alzheimer’s and Parkinson’s diseases, and major depressive disorder. HDAC6-selective inhibitors have therapeutic potential, but in the CNS drug space the development of highly brain penetrant HDAC inhibitors has been a persistent challenge. Moreover, no tool exists to directly characterize HDAC6 and its related biol. in the living human brain. Here, we report a highly brain penetrant HDAC6 inhibitor, Bavarostat, that exhibits excellent HDAC6 selectivity (>80-fold over all other Zn-containing HDAC paralogues), modulates tubulin acetylation selectively over histone acetylation, and has excellent brain penetrance. We further demonstrate that Bavarostat can be radiolabeled with 18F by deoxyfluorination through in situ formation of a ruthenium π-complex of the corresponding phenol precursor: the only method currently suitable for synthesis of [18F]Bavarostat. Finally, by using [18F]Bavarostat in a series of rodent and nonhuman primate imaging experiments, we demonstrate its utility for mapping HDAC6 in the living brain, which sets the stage for first-in-human neurochem. imaging of this important target.

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Reference:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics