Abstract
Modifying FTY720, an immunosuppressant modulator, led to a new series of well phosphorylated tetralin analogs as potent S1P1 receptor agonists. The stereochemistry effect of tetralin ring was probed, and (-)-(R)-2-amino-2-((S)-6-octyl-1,2,3,4-tetrahydronaphthalen-2-yl)propan-1-ol was identified as a good SphK2 substrate and potent S1P1 agonist with good oral bioavailability.
2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Administration, Oral
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Animals
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Crystallography, X-Ray
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Immunosuppressive Agents / chemistry
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Immunosuppressive Agents / metabolism
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Immunosuppressive Agents / pharmacokinetics
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Immunosuppressive Agents / pharmacology*
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Lymphopenia / chemically induced
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Mice
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Models, Molecular
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Multiple Sclerosis / drug therapy
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Phosphorylation
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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Prodrugs / chemistry
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Prodrugs / metabolism
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Prodrugs / pharmacokinetics
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Prodrugs / pharmacology*
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Receptors, Lysosphingolipid / agonists*
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Receptors, Lysosphingolipid / metabolism*
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Structure-Activity Relationship
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Tetrahydronaphthalenes / chemistry
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Tetrahydronaphthalenes / metabolism
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Tetrahydronaphthalenes / pharmacokinetics
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Tetrahydronaphthalenes / pharmacology*
Substances
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Immunosuppressive Agents
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Prodrugs
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Receptors, Lysosphingolipid
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Tetrahydronaphthalenes
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Phosphotransferases (Alcohol Group Acceptor)
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sphingosine kinase
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tetralin