title: Discovery of 3,4-Dihydropyrimidin-2(1H)-ones As a Novel Class of Potent and Selective A2B Adenosine Receptor Antagonists.
abstract: We describe the discovery and optimization of 3,4-dihydropyrimidin-2(1H)-ones as a novel family of (nonxanthine) A2B receptor antagonists that exhibit an unusually high selectivity profile. The Biginelli-based hit optimization process enabled a thoughtful exploration of the structure-activity and structure-selectivity relationships for this chemotype, enabling the identification of ligands that combine structural simplicity with excellent hA2B AdoR affinity and remarkable selectivity profiles.
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain ; Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain.
authors.forename: Abel
authors.initials: A
authors.lastname: Crespo
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain ; Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: El Maatougui
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Biagini
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain ; Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain.
authors.forename: Jhonny
authors.initials: J
authors.lastname: Azuaje
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain ; Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Coelho
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Brea
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Loza
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Cadavid
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain.
authors.forename: Xerardo
authors.initials: X
authors.lastname: García-Mera
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Biomedical Center , Uppsala SE-75124, Sweden.
authors.forename: Hugo
authors.initials: H
authors.lastname: Gutiérrez-de-Terán
authors.affiliation: Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain ; Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain ; Center for Research in Biological Chemistry and Molecular Materials (CIQUS), Institute of Industrial Pharmacy, Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela , Santiago de Compostela 15782, Spain.
authors.forename: Eddy
authors.initials: E
authors.lastname: Sotelo
keywords: 3,4-dihydropyrimidin-2(1H)-ones; A2B receptor antagonists; Adenosine antagonists; Biginelli reaction