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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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
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author Mrozowski, Roman M.
Sandusky, Zachary M.
Vemula, Rajender
Wu, Bulan
Zhang, Qi
Lannigan, Deborah A.
O’Doherty, George A.
author_facet Mrozowski, Roman M.
Sandusky, Zachary M.
Vemula, Rajender
Wu, Bulan
Zhang, Qi
Lannigan, Deborah A.
O’Doherty, George A.
author_sort Mrozowski, Roman M.
collection PubMed
description [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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spelling pubmed-42515252015-11-05 De Novo Synthesis and Biological Evaluation of C6″-Substituted C4″-Amide Analogues of SL0101 Mrozowski, Roman M. Sandusky, Zachary M. Vemula, Rajender Wu, Bulan Zhang, Qi Lannigan, Deborah A. O’Doherty, George A. Org Lett [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. American Chemical Society 2014-11-05 2014-11-21 /pmc/articles/PMC4251525/ /pubmed/25372628 http://dx.doi.org/10.1021/ol503012k Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Mrozowski, Roman M.
Sandusky, Zachary M.
Vemula, Rajender
Wu, Bulan
Zhang, Qi
Lannigan, Deborah A.
O’Doherty, George A.
De Novo Synthesis and Biological Evaluation of C6″-Substituted C4″-Amide Analogues of SL0101
title De Novo Synthesis and Biological Evaluation of C6″-Substituted C4″-Amide Analogues of SL0101
title_full De Novo Synthesis and Biological Evaluation of C6″-Substituted C4″-Amide Analogues of SL0101
title_fullStr De Novo Synthesis and Biological Evaluation of C6″-Substituted C4″-Amide Analogues of SL0101
title_full_unstemmed De Novo Synthesis and Biological Evaluation of C6″-Substituted C4″-Amide Analogues of SL0101
title_short De Novo Synthesis and Biological Evaluation of C6″-Substituted C4″-Amide Analogues of SL0101
title_sort de novo synthesis and biological evaluation of c6″-substituted c4″-amide analogues of sl0101
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251525/
https://www.ncbi.nlm.nih.gov/pubmed/25372628
http://dx.doi.org/10.1021/ol503012k
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