Diversity Synthesis of Complex Pyridines Yields a Probe of a Neurotrophic Signaling Pathway

[Image: see text] Recognizing the value of including complex pyridines in small-molecule screening collections, we developed a previously unexplored [2 + 2 + 2]-cycloaddition of silyl-tethered diynes with nitriles. The tether provides high regioselectivity, while the solvent THF allows catalytic CpC...

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Autores principales: Gray, B. Lawrence, Wang, Xiang, Brown, W. Colby, Kuai, Letian, Schreiber, Stuart L.
Formato: Texto
Lenguaje:English
Publicado: American Chemical Society 2008
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652409/
https://www.ncbi.nlm.nih.gov/pubmed/18510333
http://dx.doi.org/10.1021/ol8004936
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author Gray, B. Lawrence
Wang, Xiang
Brown, W. Colby
Kuai, Letian
Schreiber, Stuart L.
author_facet Gray, B. Lawrence
Wang, Xiang
Brown, W. Colby
Kuai, Letian
Schreiber, Stuart L.
author_sort Gray, B. Lawrence
collection PubMed
description [Image: see text] Recognizing the value of including complex pyridines in small-molecule screening collections, we developed a previously unexplored [2 + 2 + 2]-cycloaddition of silyl-tethered diynes with nitriles. The tether provides high regioselectivity, while the solvent THF allows catalytic CpCo(CO)(2) to be used without exogenous irradiation. One of the resulting bicyclic and monocyclic (desilylated) pyridines was identified as an inhibitor of neuregulin-induced neurite outgrowth (EC(50) = 0.30 µM) in a screen that probes a pathway likely to be involved in breast cancers and schizophrenia.
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spelling pubmed-26524092009-03-20 Diversity Synthesis of Complex Pyridines Yields a Probe of a Neurotrophic Signaling Pathway Gray, B. Lawrence Wang, Xiang Brown, W. Colby Kuai, Letian Schreiber, Stuart L. Org Lett [Image: see text] Recognizing the value of including complex pyridines in small-molecule screening collections, we developed a previously unexplored [2 + 2 + 2]-cycloaddition of silyl-tethered diynes with nitriles. The tether provides high regioselectivity, while the solvent THF allows catalytic CpCo(CO)(2) to be used without exogenous irradiation. One of the resulting bicyclic and monocyclic (desilylated) pyridines was identified as an inhibitor of neuregulin-induced neurite outgrowth (EC(50) = 0.30 µM) in a screen that probes a pathway likely to be involved in breast cancers and schizophrenia. American Chemical Society 2008-05-30 2008-07-03 /pmc/articles/PMC2652409/ /pubmed/18510333 http://dx.doi.org/10.1021/ol8004936 Text en Copyright © 2008 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org. 40.75
spellingShingle Gray, B. Lawrence
Wang, Xiang
Brown, W. Colby
Kuai, Letian
Schreiber, Stuart L.
Diversity Synthesis of Complex Pyridines Yields a Probe of a Neurotrophic Signaling Pathway
title Diversity Synthesis of Complex Pyridines Yields a Probe of a Neurotrophic Signaling Pathway
title_full Diversity Synthesis of Complex Pyridines Yields a Probe of a Neurotrophic Signaling Pathway
title_fullStr Diversity Synthesis of Complex Pyridines Yields a Probe of a Neurotrophic Signaling Pathway
title_full_unstemmed Diversity Synthesis of Complex Pyridines Yields a Probe of a Neurotrophic Signaling Pathway
title_short Diversity Synthesis of Complex Pyridines Yields a Probe of a Neurotrophic Signaling Pathway
title_sort diversity synthesis of complex pyridines yields a probe of a neurotrophic signaling pathway
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652409/
https://www.ncbi.nlm.nih.gov/pubmed/18510333
http://dx.doi.org/10.1021/ol8004936
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