title: Targeting adenosine receptors with coumarins: synthesis and binding activities of amide and carbamate derivatives.
abstract: OBJECTIVE
  With the aim of finding the structural features governing binding activity and selectivity against adenosine receptors (ARs), several 3-subtituted coumarins with amide (compounds 3-6) and carbamate (7-9) functions were synthesized. To study its possible influence on the binding activity and selectivity, a hydroxyl substituent was also introduced at position 4 of the coumarin moiety.
  
  
  METHODS
  A new series of coumarins (3-9) were synthesized and evaluated by radioligand binding studies towards ARs.
  
  
  RESULTS
  None of the 4-hydroxy derivatives (4, 8 and 9) showed binding affinity for any of the ARs. None of the compounds interacted with the hA(2B) AR (K(i) > 100,000 nM). Compounds 3, 5, 6 and 7 had different activity profiles with dissimilar binding affinity and selectivity towards human A₁, A(2A) and A₃ ARs.
  
  
  CONCLUSIONS
  The most remarkable derivative is compound 7, which presents the best affinity and selectivity for the A₃ adenosine receptor (K(i) = 5500 nM).
authors.affiliation: CIQUP/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, Portugal. mariajoao.correiapinto@rai.usc.es
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Matos
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gaspar
authors.forename: Sonja
authors.initials: S
authors.lastname: Kachler
authors.forename: Karl-Norbert
authors.initials: KN
authors.lastname: Klotz
authors.forename: Fernanda
authors.initials: F
authors.lastname: Borges
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D058917:Adenosine A2 Receptor Antagonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D058918:Adenosine A3 Receptor Antagonists / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003374:Coumarins / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D043682:Receptor, Adenosine A1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D000577:Amides; D002219:Carbamates; D003374:Coumarins; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D011994:Recombinant Proteins