title: Chalcone-based derivatives as new scaffolds for hA3 adenosine receptor antagonists.
abstract: OBJECTIVE
  With the aim of finding new adenosine receptor (AR) ligands based on the chalcone scaffold, we report the synthesis of a new series of coumarin-chalcone hybrids and the pharmacological characterization of their actions at four subtypes of AR.
  
  
  METHODS
  The synthesized compounds 5-10 were characterized in radioligand binding (A1 , A2A and A3 ) and adenylyl cyclase activity assays (A2B ) to determine the affinity of the compounds for the four human AR (hAR) subtypes.
  
  
  RESULTS
  Coumarin-chalcone hybrids were found to be ligands with a novel structure, not reported thus far, that showed varying affinity and selectivity for AR subtypes.
  
  
  CONCLUSIONS
  The coumarin-chalcone hybrids in which ring B of the chalcone scaffold was a thiophene (compounds 5 and 9) were found to be the most potent compounds of the series. Compound 9, in which ring A of the chalcone moiety was the phenyl ring of the coumarin, showed similar activity against hA1 , hA2A and hA3 ARs, while compound 5, in which ring A of the chalcone was substituted by the benzopyrone ring of the coumarin moiety, showed similar activity only at the hA3 AR and, therefore, was deemed to be selective (Ki (dissociation constant) = 5160 nm).
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Saleta
authors.initials: S
authors.lastname: Vazquez-Rodriguez
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Matos
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.forename: Fernanda
authors.initials: F
authors.lastname: Borges
authors.forename: Sonja
authors.initials: S
authors.lastname: Kachler
authors.forename: Karl-Norbert
authors.initials: KN
authors.lastname: Klotz
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002599:Chalcone / Q000737:chemistry / Q000494:pharmacology*; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008024:Ligands; D058915:Purinergic P1 Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D011869:Radioligand Assay; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry
chemical_list: D003374:Coumarins; D008024:Ligands; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D013876:Thiophenes; D002599:Chalcone; C030123:coumarin