Abstract
Screening of our in-house compound collection led to the discovery of 5-bromo-6-amino-2-isoquinoline 1 as a weak inhibitor of IMPDH. Subsequent optimization of 1 afforded a series of novel 2-isoquinolinoaminooxazole-based inhibitors, represented by 17, with single-digit nanomolar potency against the enzyme.
MeSH terms
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Drug Evaluation, Preclinical
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Escherichia coli / enzymology
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Humans
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IMP Dehydrogenase / antagonists & inhibitors*
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Isoquinolines / chemical synthesis*
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Isoquinolines / pharmacology*
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NAD / metabolism
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Oxazoles / chemical synthesis*
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Oxazoles / pharmacology*
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Isoquinolines
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Oxazoles
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NAD
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IMP Dehydrogenase