Abstract
The first asymmetric synthesis of (S)- and (R)-5-hydroxythalidomides, one of thalidomide's major metabolites, was achieved using HMDS/ZnBr(2)-induced imidation as a key reaction. 5-Hydroxythalidomide was found to be configurationally more stable than thalidomide at physiological pH. Stereochemical biological effects of thalidomide and 5-hydroxythalidomide on anti-angiogenesis and antitumor activities were also investigated using racemic and pure enantiomers.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / chemical synthesis*
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology*
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Line
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Drug Screening Assays, Antitumor
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Humans
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Hydrogen-Ion Concentration
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Stereoisomerism
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Thalidomide / analogs & derivatives*
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Thalidomide / chemical synthesis
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Thalidomide / chemistry*
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Thalidomide / metabolism
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Thalidomide / pharmacology
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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5-hydroxythalidomide
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Thalidomide