title: Highly potent aminopyridines as Syk kinase inhibitors.
abstract: A novel class of potent Syk inhibitors has been developed from rational design. Highly potent aminopyridine derivatives bearing a 4-trifluoromethyl-2-pyridyl motif and represented by compound 13b IC(50): 0.6 nM were identified. Substitution by a 2-pyrazinyl motif and SAR expansion in position 4 of the central core provided diverse potent non-cytotoxic Syk inhibitors showing nanomolar activity inhibiting human mast cell line LAD2 degranulation.
authors.affiliation: Almirall-Barcelona Science Park Unit, Barcelona Science Park, 08028 Barcelona, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Castillo
authors.forename: Pilar
authors.initials: P
authors.lastname: Forns
authors.forename: Montse
authors.initials: M
authors.lastname: Erra
authors.forename: Marta
authors.initials: M
authors.lastname: Mir
authors.forename: Manel
authors.initials: M
authors.lastname: López
authors.forename: Mónica
authors.initials: M
authors.lastname: Maldonado
authors.forename: Adelina
authors.initials: A
authors.lastname: Orellana
authors.forename: Cristina
authors.initials: C
authors.lastname: Carreño
authors.forename: Isabel
authors.initials: I
authors.lastname: Ramis
authors.forename: Montserrat
authors.initials: M
authors.lastname: Miralpeix
authors.forename: Bernat
authors.initials: B
authors.lastname: Vidal
mesh_terms: D000631:Aminopyridines / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000072377:Syk Kinase
chemical_list: D000631:Aminopyridines; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase