Abstract
A series of oxazolidin-2-one-4-carboxylic amide compounds (1a-f) were designed and synthesized as the non-phosphate S1P(1) receptor agonists. The single crystal of 1e was prepared and solved to elucidate the structure of 1a-f. EC(50) of 1a-d were about 1.1-3.6 μM in S1P(1) Redistribution® assay, and their cytotoxicity was 8-40-fold lower than FTY720. Though its S1P(1) agonist activities in vitro were about 1000-folds weaker than (S)-FTY720-P, at a dose of 10mg/Kg, the immunosuppressive effects of 1a were comparable to FTY720. So oxazolidin-2-one-4-carboxylic amide derivatives were found as potential immunomodulator, compound 1a could be considered as a lead compound, rational modifications of 1a are anticipated using medicinal chemistry techniques and molecular modeling to obtain analogs with higher affinity and better clinical therapeutic properties.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemical synthesis*
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Amides / pharmacology*
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Amino Acids / chemistry
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Benzamides / chemical synthesis*
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Benzamides / pharmacology
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Catalytic Domain
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Fingolimod Hydrochloride
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Humans
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Hydrogen Bonding
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Immunologic Factors / pharmacology*
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Immunosuppressive Agents / pharmacology
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Inhibitory Concentration 50
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Models, Chemical
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Models, Molecular
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Molecular Conformation
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Oxazolone / analogs & derivatives*
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Oxazolone / chemical synthesis
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Oxazolone / pharmacology
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Propylene Glycols / pharmacology
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Receptors, Lysosphingolipid / agonists
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Sphingosine / analogs & derivatives
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Sphingosine / pharmacology
Substances
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Amides
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Amino Acids
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Benzamides
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Immunologic Factors
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Immunosuppressive Agents
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Propylene Glycols
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Receptors, Lysosphingolipid
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oxazolin-2-one-4-carboxamide
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Oxazolone
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Fingolimod Hydrochloride
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Sphingosine