title: Pyrazin-2(1H)-ones as a novel class of selective A3 adenosine receptor antagonists.
abstract: BACKGROUND
  A3AR antagonists are promising drug candidates as neuroprotective agents as well as for the treatment of inflammation or glaucoma. The most widely known A3AR antagonists are derived from polyheteroaromatic scaffolds, which usually show poor pharmacokinetic properties. Accordingly, the identification of structurally simple A3AR antagonists by the exploration of novel diversity spaces is a challenging goal.
  
  
  RESULTS
  A convergent and efficient Ugi-based multicomponent approach enabled the discovery of pyrazin-2(1H)-ones as a novel class of A3AR antagonists. A combined experimental/computational strategy accelerated the establishment of the most salient features of the structure-activity and structure-selectivity relationships in this series.
  
  
  CONCLUSIONS
  The optimization process provided pyrazin-2(1H)-ones with improved affinity and a plausible hypothesis regarding their binding modes was proposed.
authors.affiliation: Center for Research in Biological Chemistry & Molecular Materials (CIQUS), University of Santiago de Compostela, 15782, Spain.|Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain.
authors.forename: Jhonny
authors.initials: J
authors.lastname: Azuaje
authors.affiliation: Center for Research in Biological Chemistry & Molecular Materials (CIQUS), University of Santiago de Compostela, 15782, Spain.|Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Carbajales
authors.affiliation: Center for Research in Biological Chemistry & Molecular Materials (CIQUS), University of Santiago de Compostela, 15782, Spain.|Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: González-Gómez
authors.affiliation: Center for Research in Biological Chemistry & Molecular Materials (CIQUS), University of Santiago de Compostela, 15782, Spain.|Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Coelho
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Caamaño
authors.affiliation: Department of Cell & Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-75124, Uppsala, Sweden.
authors.forename: Hugo
authors.initials: H
authors.lastname: Gutiérrez-de-Terán
authors.affiliation: Center for Research in Biological Chemistry & Molecular Materials (CIQUS), University of Santiago de Compostela, 15782, Spain.|Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782, Spain.
authors.forename: Eddy
authors.initials: E
authors.lastname: Sotelo
mesh_terms: D058918:Adenosine A3 Receptor Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D062105:Molecular Docking Simulation; D011719:Pyrazines / Q000737:chemistry* / Q000494:pharmacology*; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D011719:Pyrazines; D043684:Receptor, Adenosine A3