title: Synthesis and adenosine receptors binding affinities of a series of 3-arylcoumarins.
abstract: OBJECTIVE
  In the present communication, we report the synthesis, pharmacological evaluation, theoretical evaluation of absorption, distribution, metabolism and excretion properties and structure-activity relationship study of a selected series of 3-arylcoumarins (compounds 1-9). Adenosine receptors (ARs) binding activity and selectivity of the synthesized compounds 1-9 were evaluated in this study. Different substituents were introduced in both benzene rings of the evaluated scaffold, at positions 6 and 3' or 4' of the moiety. The lack of data on the 3-arylcoumarin scaffold encouraged us to explore the ARs' binding activity of a selected series of derivatives.
  
  
  METHODS
  A new series of coumarins (compounds 1-9) were synthesized and evaluated by radioligand binding studies towards ARs.
  
  
  RESULTS
  Analysing the experimental data, it can be observed that neither the simple 3-arylcoumarin nor the 4'-nitro derivatives presented detectable binding affinity for the evaluated receptors, although most of the other substituted derivatives have good binding affinity profiles, especially against the hA1 /hA3 or only hA3 AR.
  
  
  CONCLUSIONS
  The most remarkable derivative is compound 2, presenting the best affinity for hA3 AR (Ki  = 2680 nM) and significant selectivity for this subtype.
authors.affiliation: CIQUP/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, Portugal; Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Matos
authors.forename: Veronika
authors.initials: V
authors.lastname: Hogger
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gaspar
authors.forename: Sonja
authors.initials: S
authors.lastname: Kachler
authors.forename: Fernanda
authors.initials: F
authors.lastname: Borges
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.forename: Karl-Norbert
authors.initials: KN
authors.lastname: Klotz
mesh_terms: D000818:Animals; D016466:CHO Cells; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D011485:Protein Binding; D058915:Purinergic P1 Receptor Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D011869:Radioligand Assay; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism*
chemical_list: D003374:Coumarins; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1
keywords: 3-arylcoumarins; absorption, distribution, metabolism and excretion properties; adenosine receptors binding activity; structure-activity relationship study