Abstract
Combined photochemical arylation, "nuisance effect" (SN Ar) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein-ligand structure determination. Reactions were deliberately allowed to run "out of control" in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with SN Ar processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.
© 2020 Wiley-VCH GmbH.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzene Derivatives / chemical synthesis*
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Benzene Derivatives / metabolism
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Catalysis
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Chemistry Techniques, Synthetic / methods
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Coordination Complexes / chemistry
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Crystallography, X-Ray
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / metabolism
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Feasibility Studies
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Humans
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Nudix Hydrolases
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Palladium / chemistry
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Proof of Concept Study
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Protein Binding
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Pyridines / chemical synthesis
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Pyridines / metabolism
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Pyrophosphatases / metabolism
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Pyrrolidinones / chemical synthesis
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Pyrrolidinones / metabolism
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Small Molecule Libraries / chemical synthesis*
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Small Molecule Libraries / metabolism
Substances
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Benzene Derivatives
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Coordination Complexes
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Enzyme Inhibitors
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Pyridines
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Pyrrolidinones
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Small Molecule Libraries
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Palladium
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Pyrophosphatases