Abstract
Autotaxin (ATX) is an attractive pharmacological target due to its lysophospholipase D activity which leads to the production of lysophosphatidic acid (LPA). Blockage of ATX produced LPA by small molecules could be a potential anticancer chemotherapy. In our previous study, we have identified the two beta-hydroxy phosphonate analogs of LPA (compounds f17 and f18) as ATX inhibitors. With this work, we investigated alpha- and beta-substituted phosphonate analogs of LPA and evaluated them for ATX inhibitory activity. The stereochemistry of beta-hydroxy phosphonates was also studied.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Lysophospholipids / chemistry*
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Lysophospholipids / pharmacology*
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Magnetic Resonance Spectroscopy
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Molecular Structure
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Organophosphonates / chemical synthesis*
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Organophosphonates / chemistry
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Organophosphonates / pharmacology*
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Phosphodiesterase Inhibitors / chemical synthesis*
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Phosphodiesterase Inhibitors / chemistry
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Phosphodiesterase Inhibitors / pharmacology*
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Phosphoric Diester Hydrolases / metabolism
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Pyrophosphatases / antagonists & inhibitors*
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Pyrophosphatases / metabolism
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Structure-Activity Relationship
Substances
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Lysophospholipids
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Organophosphonates
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Phosphodiesterase Inhibitors
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Phosphoric Diester Hydrolases
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Pyrophosphatases
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lysophosphatidic acid