Abstract
In an effort to improve upon the in vivo half-life of the known ribosomal s6 kinase (RSK) inhibitor SL0101, C4″-amide/C6″-alkyl substituted analogues of SL0101 were synthesized and evaluated in cell-based assays. The analogues were prepared using a de novo asymmetric synthetic approach, which featured Pd-π-allylic catalyzed glycosylation for the introduction of a C4″-azido group. Surprisingly replacement of the C4″-acetate with a C4″-amide resulted in analogues that were no longer specific for RSK in cell-based assays.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amides / chemistry*
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Benzopyrans / chemical synthesis*
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Benzopyrans / chemistry
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Benzopyrans / pharmacology
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Glycosylation
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Half-Life
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Molecular Structure
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Monosaccharides / chemical synthesis*
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Monosaccharides / chemistry
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Monosaccharides / pharmacology
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / chemical synthesis
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / pharmacology
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Ribosomal Protein S6 Kinases, 90-kDa / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Amides
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Benzopyrans
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Monosaccharides
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SL0101
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Protein Serine-Threonine Kinases
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Ribosomal Protein S6 Kinases, 90-kDa