Discovery of LAS101057: A Potent, Selective, and Orally Efficacious A2B Adenosine Receptor Antagonist
ACS Medicinal Chemistry Letters2010Vol. 2(3), pp. 213–218
Citations Over TimeTop 19% of 2010 papers
Paul Eastwood, Cristina Esteve, Jacob González, Sı́lvia Fonquerna, Josep Aiguadé, Inés Carranco, Teresa Domènech, Mònica Aparici, Montserrat Miralpeix, Joan Albertí, Mònica Córdoba, Raquel M. Fernández, Mercè Pont, Núria Godessart, Neus Prats, Marı́a Isabel Loza, Marı́a Isabel Cadavid, Arsenio Nueda, Bernat Vidal
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.
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