title: The Guareschi Pyridine Scaffold as a Valuable Platform for the Identification of Selective PI3K Inhibitors.
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.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale "A. Avogadro", Largo Donegani 2, Novara 28100, Italy. ubaldina.galli@uniupo.it.
authors.forename: Ubaldina
authors.initials: U
authors.lastname: Galli
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Via Nizza 52, Torino 10126, Italy. elisa.ciraolo@unito.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ciraolo
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale "A. Avogadro", Largo Donegani 2, Novara 28100, Italy. alberto.massarotti@uniupo.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Massarotti
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Via Nizza 52, Torino 10126, Italy. jeanpiero.margaria@unito.it.
authors.forename: Jean Piero
authors.initials: JP
authors.lastname: Margaria
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale "A. Avogadro", Largo Donegani 2, Novara 28100, Italy. giovanni.sorba@uniupo.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sorba
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Via Nizza 52, Torino 10126, Italy. emilio.hirsch@unito.it.
authors.forename: Emilio
authors.initials: E
authors.lastname: Hirsch
authors.affiliation: Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale "A. Avogadro", Largo Donegani 2, Novara 28100, Italy. giancesare.tron@uniupo.it.
authors.forename: Gian Cesare
authors.initials: GC
authors.lastname: Tron
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D041681:NIH 3T3 Cells; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines
keywords: Guareschi reaction; PI3 kinase; isoforms; pyridine; selectivity