title: Novel triazolopyridylbenzamides as potent and selective p38α inhibitors.
abstract: A new class of p38α inhibitors based on a biaryl-triazolopyridine scaffold was investigated. X-ray crystallographic data of the initial lead compound cocrystallised with p38α was crucial in order to uncover a unique binding mode of the inhibitor to the hinge region via a pair of water molecules. Synthesis and SAR was directed towards the improvement of binding affinity, as well as ADME properties for this new class of p38α inhibitors and ultimately afforded compounds showing good in vivo efficacy.
authors.affiliation: Almirall Research Center, Almirall SA, Ctra. Laureà Miró 408, E-08980 Sant, Feliu de Llobregat, Barcelona, Spain. josep.aiguade@almirall.com
authors.forename: Josep
authors.initials: J
authors.lastname: Aiguadé
authors.forename: Cristina
authors.initials: C
authors.lastname: Balagué
authors.forename: Inés
authors.initials: I
authors.lastname: Carranco
authors.forename: Francisco
authors.initials: F
authors.lastname: Caturla
authors.forename: María
authors.initials: M
authors.lastname: Domínguez
authors.forename: Paul
authors.initials: P
authors.lastname: Eastwood
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteve
authors.forename: Jacob
authors.initials: J
authors.lastname: González
authors.forename: Wenceslao
authors.initials: W
authors.lastname: Lumeras
authors.forename: Adelina
authors.initials: A
authors.lastname: Orellana
authors.forename: Sara
authors.initials: S
authors.lastname: Preciado
authors.forename: Ramón
authors.initials: R
authors.lastname: Roca
authors.forename: Laura
authors.initials: L
authors.lastname: Vidal
authors.forename: Bernat
authors.initials: B
authors.lastname: Vidal
mesh_terms: D001549:Benzamides / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D047428:Protein Kinase Inhibitors; D048308:Mitogen-Activated Protein Kinase 14