Abstract
The first enantioselective synthesis of chiral isosteric phosphonate analogues of FTY720 is described. One of these analogues, FTY720-(E)-vinylphosphonate (S)-5, but not its R enantiomer, elicited a potent antiapoptotic effect in intestinal epithelial cells, suggesting that it exerts its action via the enantioselective activation of a receptor. (S)-5 failed to activate the sphingosine 1-phosphate type 1 (S1P(1)) receptor.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Cells, Cultured
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Fingolimod Hydrochloride
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Humans
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Immunosuppressive Agents / chemical synthesis*
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Immunosuppressive Agents / pharmacology
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Intestinal Mucosa / drug effects
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Molecular Structure
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Organophosphonates / chemical synthesis*
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Organophosphonates / chemistry
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Propylene Glycols / chemical synthesis*
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Propylene Glycols / chemistry
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Propylene Glycols / pharmacology
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Receptors, Lysosphingolipid / drug effects
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Sphingosine / analogs & derivatives*
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Sphingosine / chemical synthesis
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Sphingosine / chemistry
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Sphingosine / pharmacology
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Stereoisomerism
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Vinyl Compounds / chemical synthesis*
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Vinyl Compounds / chemistry
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Vinyl Compounds / pharmacology
Substances
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((E)-3-amino-5-(4-heptylphenyl)-3-(hydroxymethyl)pent-1-enyl)phosphonic acid
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Immunosuppressive Agents
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Organophosphonates
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Propylene Glycols
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Receptors, Lysosphingolipid
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Vinyl Compounds
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vinylphosphonic acid
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Fingolimod Hydrochloride
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Sphingosine