Abstract
With the aim of discovering a novel class of fructose-1,6-bisphosphatase (FBPase) inhibitors, a series of compounds based on tricyclic scaffolds was synthesized. Extensive SAR studies led to the finding of 8l with an IC50 value of 0.013 microM against human FBPase. An X-ray crystallographic study revealed that 8l bound at AMP binding sites of human liver FBPase with hydrogen bonding interactions similar to AMP.
MeSH terms
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Benzothiazoles / chemical synthesis*
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Benzothiazoles / chemistry
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Benzothiazoles / pharmacology
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Binding Sites
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Crystallography, X-Ray
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Fructose-Bisphosphatase / antagonists & inhibitors*
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Fructose-Bisphosphatase / metabolism
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Gluconeogenesis
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Heterocyclic Compounds, 3-Ring / chemical synthesis*
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Heterocyclic Compounds, 3-Ring / chemistry
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Heterocyclic Compounds, 3-Ring / pharmacology
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Humans
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Hydrogen Bonding
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Organophosphates / chemical synthesis*
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Organophosphates / chemistry
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Organophosphates / pharmacology
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Organophosphonates / chemical synthesis*
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Organophosphonates / chemistry
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Organophosphonates / pharmacology
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Structure-Activity Relationship
Substances
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Benzothiazoles
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Enzyme Inhibitors
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Heterocyclic Compounds, 3-Ring
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Organophosphates
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Organophosphonates
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Fructose-Bisphosphatase