The Guareschi Pyridine Scaffold as a Valuable Platform for the Identification of Selective PI3K Inhibitors

A novel series of 4-aryl-3-cyano-2-(3-hydroxyphenyl)-6-morpholino-pyridines have been designed as potential phosphatidylinositol-3-kinase (PI3K) inhibitors. The compounds have been synthesized using the Guareschi reaction to prepare the key 4-aryl-3-cyano-2,6-dihydroxypyridine intermediate. A differ...

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Detalles Bibliográficos
Autores principales: Galli, Ubaldina, Ciraolo, Elisa, Massarotti, Alberto, Margaria, Jean Piero, Sorba, Giovanni, Hirsch, Emilio, Tron, Gian Cesare
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332036/
https://www.ncbi.nlm.nih.gov/pubmed/26393561
http://dx.doi.org/10.3390/molecules200917275
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author Galli, Ubaldina
Ciraolo, Elisa
Massarotti, Alberto
Margaria, Jean Piero
Sorba, Giovanni
Hirsch, Emilio
Tron, Gian Cesare
author_facet Galli, Ubaldina
Ciraolo, Elisa
Massarotti, Alberto
Margaria, Jean Piero
Sorba, Giovanni
Hirsch, Emilio
Tron, Gian Cesare
author_sort Galli, Ubaldina
collection PubMed
description A novel series of 4-aryl-3-cyano-2-(3-hydroxyphenyl)-6-morpholino-pyridines have been designed as potential phosphatidylinositol-3-kinase (PI3K) inhibitors. The compounds have been synthesized using the Guareschi reaction to prepare the key 4-aryl-3-cyano-2,6-dihydroxypyridine intermediate. A different selectivity according to the nature of the aryl group has been observed. Compound 9b is a selective inhibitor against the PI3Kα isoform, maintaining a good inhibitory activity. Docking studies were also performed in order to rationalize its profile of selectivity.
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spelling pubmed-63320362019-01-24 The Guareschi Pyridine Scaffold as a Valuable Platform for the Identification of Selective PI3K Inhibitors Galli, Ubaldina Ciraolo, Elisa Massarotti, Alberto Margaria, Jean Piero Sorba, Giovanni Hirsch, Emilio Tron, Gian Cesare Molecules Article A novel series of 4-aryl-3-cyano-2-(3-hydroxyphenyl)-6-morpholino-pyridines have been designed as potential phosphatidylinositol-3-kinase (PI3K) inhibitors. The compounds have been synthesized using the Guareschi reaction to prepare the key 4-aryl-3-cyano-2,6-dihydroxypyridine intermediate. A different selectivity according to the nature of the aryl group has been observed. Compound 9b is a selective inhibitor against the PI3Kα isoform, maintaining a good inhibitory activity. Docking studies were also performed in order to rationalize its profile of selectivity. MDPI 2015-09-18 /pmc/articles/PMC6332036/ /pubmed/26393561 http://dx.doi.org/10.3390/molecules200917275 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Galli, Ubaldina
Ciraolo, Elisa
Massarotti, Alberto
Margaria, Jean Piero
Sorba, Giovanni
Hirsch, Emilio
Tron, Gian Cesare
The Guareschi Pyridine Scaffold as a Valuable Platform for the Identification of Selective PI3K Inhibitors
title The Guareschi Pyridine Scaffold as a Valuable Platform for the Identification of Selective PI3K Inhibitors
title_full The Guareschi Pyridine Scaffold as a Valuable Platform for the Identification of Selective PI3K Inhibitors
title_fullStr The Guareschi Pyridine Scaffold as a Valuable Platform for the Identification of Selective PI3K Inhibitors
title_full_unstemmed The Guareschi Pyridine Scaffold as a Valuable Platform for the Identification of Selective PI3K Inhibitors
title_short The Guareschi Pyridine Scaffold as a Valuable Platform for the Identification of Selective PI3K Inhibitors
title_sort guareschi pyridine scaffold as a valuable platform for the identification of selective pi3k inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332036/
https://www.ncbi.nlm.nih.gov/pubmed/26393561
http://dx.doi.org/10.3390/molecules200917275
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