The guareschi pyridine scaffold as a valuable platform for the identification of selective PI3K inhibitors

Ubaldina Galli; Elisa Ciraolo; Alberto Massarotti; Jean Piero Margaria; Giovanni Sorba; Emilio Hirsch; Gian Cesare Tron

doi:10.3390/molecules200917275

The guareschi pyridine scaffold as a valuable platform for the identification of selective PI3K inhibitors

Ubaldina Galli
, Elisa Ciraolo
, Alberto Massarotti
, Jean Piero Margaria
, Giovanni Sorba
, Emilio Hirsch
, Gian Cesare Tron

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	17275-17287
Number of pages	13
Journal	Molecules
Volume	20
Issue number	9
DOIs	https://doi.org/10.3390/molecules200917275
Publication status	Published - 1 Sept 2015

Keywords

Guareschi reaction
Isoforms
PI3 kinase
Pyridine
Selectivity

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10.3390/molecules200917275

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abstract = "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.",

keywords = "Guareschi reaction, Isoforms, PI3 kinase, Pyridine, Selectivity",

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AU - Galli, Ubaldina

AU - Ciraolo, Elisa

AU - Massarotti, Alberto

AU - Margaria, Jean Piero

AU - Sorba, Giovanni

AU - Hirsch, Emilio

AU - Tron, Gian Cesare

PY - 2015/9/1

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AB - 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.

KW - Guareschi reaction

KW - Isoforms

KW - PI3 kinase

KW - Pyridine

KW - Selectivity

UR - https://www.scopus.com/pages/publications/84947996205

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DO - 10.3390/molecules200917275

M3 - Article

SN - 1420-3049

VL - 20

SP - 17275

EP - 17287

JO - Molecules

JF - Molecules

IS - 9

ER -

The guareschi pyridine scaffold as a valuable platform for the identification of selective PI3K inhibitors

Abstract

Keywords

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