title: Discovery of LAS101057: A Potent, Selective, and Orally Efficacious A2B Adenosine Receptor Antagonist.
abstract: The structure-activity relationships for a series of pyrazine-based A2B adenosine receptor antagonists are described. From this work, LAS101057 (17), a potent, selective, and orally efficacious A2B receptor antagonist, was identified as a clinical development candidate. LAS101057 inhibits agonist-induced IL-6 production in human fibroblasts and is active in an ovalbumin (OVA)-sensitized mouse model after oral administration, reducing airway hyperresponsiveness to methacholine, Th2 cytokine production, and OVA-specific IgE levels.
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Paul
authors.initials: P
authors.lastname: Eastwood
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteve
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Jacob
authors.initials: J
authors.lastname: González
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fonquerna
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Aiguadé
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Carranco
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Doménech
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Aparici
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Miralpeix
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Albertí
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Córdoba
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Fernández
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Pont
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Godessart
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Prats
authors.affiliation: Discovery group "BioFarma", Faculty of Pharmacy, University of Santiago de Compostela, 15782-Santiago de Compostela, Spain.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Loza
authors.affiliation: Discovery group "BioFarma", Faculty of Pharmacy, University of Santiago de Compostela, 15782-Santiago de Compostela, Spain.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Cadavid
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Arsenio
authors.initials: A
authors.lastname: Nueda
authors.affiliation: Almirall, R&D Centre, Ctra. Laureà Miró 408, 08980-Sant Feliu de Llobregat, Barcelona, Spain.
authors.forename: Bernat
authors.initials: B
authors.lastname: Vidal
keywords: A2B adenosine receptor antagonist; clinical candidate; ovalbumin mouse model