title: Pyrazine-based Syk kinase inhibitors.
abstract: A series of aminopyrazines as inhibitors of Syk kinase activity and showing inhibition of LAD2 cells degranulation is described. Optimization of the carboxamide motif with aminomethylpiperidines provided high potency inhibiting Syk but low cellular activity. Amides of cis and trans adamantanol showed good inhibitory activity against Syk as well as remarkable activity in LAD2 cells degranulation assay.
authors.affiliation: Almirall-Barcelona Science Park Unit, Barcelona Science Park, 08028 Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Forns
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteve
authors.forename: Lorena
authors.initials: L
authors.lastname: Taboada
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Alonso
authors.forename: Adelina
authors.initials: A
authors.lastname: Orellana
authors.forename: Mónica
authors.initials: M
authors.lastname: Maldonado
authors.forename: Cristina
authors.initials: C
authors.lastname: Carreño
authors.forename: Isabel
authors.initials: I
authors.lastname: Ramis
authors.forename: Manel
authors.initials: M
authors.lastname: López
authors.forename: Montserrat
authors.initials: M
authors.lastname: Miralpeix
authors.forename: Bernat
authors.initials: B
authors.lastname: Vidal
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000072377:Syk Kinase
chemical_list: D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011719:Pyrazines; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C434445:1-adamantanol; D000218:Adamantane