De Novo Synthesis and Biological Evaluation of C6″-Substituted C4″-Amide Analogues of SL0101

[Image: see text] 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 appr...

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Detalles Bibliográficos
Autores principales: Mrozowski, Roman M., Sandusky, Zachary M., Vemula, Rajender, Wu, Bulan, Zhang, Qi, Lannigan, Deborah A., O’Doherty, George A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251525/
https://www.ncbi.nlm.nih.gov/pubmed/25372628
http://dx.doi.org/10.1021/ol503012k
Descripción
Sumario:[Image: see text] 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.

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