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
Descripción
Sumario: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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