title: 8-(2-Furyl)adenine derivatives as A₂A adenosine receptor ligands.
abstract: Selective adenosine receptor modulators are potential tools for numerous therapeutic applications, including cardiovascular, inflammatory, and neurodegenerative diseases. In this work, the synthesis and biological evaluation at the four human adenosine receptor subtypes of a series of 9-substituted 8-(2-furyl)adenine derivatives are reported. Results show that 8-(2-furyl)-9-methyladenine is endowed with high affinity at the A₂A subtype. Further modification of this compound with introduction of arylacetyl or arylcarbamoyl groups in N(6)-position takes to different effects on the A₂A affinity and in particular on the selectivity versus the other three adenosine receptor subtypes. A molecular modelling analysis at three different A₂A receptor crystal structures provides an interpretation of the obtained biological results.
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Via S. Agostino 1, I-62032 Camerino, MC, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Dal Ben
authors.forename: Michela
authors.initials: M
authors.lastname: Buccioni
authors.forename: Catia
authors.initials: C
authors.lastname: Lambertucci
authors.forename: Ajiroghene
authors.initials: A
authors.lastname: Thomas
authors.forename: Karl-Norbert
authors.initials: KN
authors.lastname: Klotz
authors.forename: Stephanie
authors.initials: S
authors.lastname: Federico
authors.forename: Barbara
authors.initials: B
authors.lastname: Cacciari
authors.forename: Giampiero
authors.initials: G
authors.lastname: Spalluto
authors.forename: Rosaria
authors.initials: R
authors.lastname: Volpini
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D043705:Receptor, Adenosine A2A / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: C000591487:8-(2-furyl)adenine; D008024:Ligands; D043705:Receptor, Adenosine A2A; D011994:Recombinant Proteins; D000225:Adenine
keywords: AR; Adenine derivatives; Adenosine receptor antagonists; Adenosine receptors; CHO; CNS; Chinese hamster ovary; DMF; EL; G protein-coupled receptor; GPCR; IL; IR; MOE; Molecular modelling; N-bromosuccinimide; NBS; Purine derivatives; Purinergic receptors; RMSD; THF; TLC; TM; adenosine receptor; central nervous system; dimethylformamide; extracellular loop; infrared; intracellular loop; molecular operating environment; pdb; protein data bank; root mean square deviation; tetrahydrofuran; thin-layer chromatography; transmembrane