title: Novel potent and highly selective human A(3) adenosine receptor antagonists belonging to the 4-amido-2-arylpyrazolo[3,4-c]quinoline series: molecular docking analysis and pharmacological studies.
abstract: The study of novel 2-arylpyrazolo[3,4-c]quinolin-4-(hetero)arylamides, designed as human (h) A(3) adenosine receptor antagonists, is reported. The new derivatives are endowed with nanomolar hA(3) receptor affinity and high selectivity versus hA(1), hA(2A) and hA(2B) receptors. Among the (hetero)aroyl residues introduced on the 4-amino group, the 2-furyl and 4-pyridyl rings turned out to be the most beneficial for hA(3) affinity (K(i)=3.4 and 5.0nM, respectively). An intensive molecular docking study to a rhodopsin-based homology model of the hA(3) receptor was carried out to obtain a 'structure-based pharmacophore model' that proved to be helpful for the interpretation of the observed affinities of the new hA(3) pyrazoloquinoline antagonists.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Laboratorio di Progettazione, Sintesi e Studio di Eterocicli Biologicamente Attivi, Università di Firenze, Polo Scientifico, Via Ugo Schiff, 6, 50019 Sesto Fiorentino, FI, Italy. vittoria.colotta@unifi.it
authors.forename: Vittoria
authors.initials: V
authors.lastname: Colotta
authors.forename: Francesca
authors.initials: F
authors.lastname: Capelli
authors.forename: Ombretta
authors.initials: O
authors.lastname: Lenzi
authors.forename: Daniela
authors.initials: D
authors.lastname: Catarzi
authors.forename: Flavia
authors.initials: F
authors.lastname: Varano
authors.forename: Daniela
authors.initials: D
authors.lastname: Poli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vincenzi
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
authors.forename: Diego
authors.initials: D
authors.lastname: Dal Ben
authors.forename: Rosaria
authors.initials: R
authors.lastname: Volpini
authors.forename: Gloria
authors.initials: G
authors.lastname: Cristalli
authors.forename: Guido
authors.initials: G
authors.lastname: Filacchioni
mesh_terms: D058918:Adenosine A3 Receptor Antagonists; D000577:Amides; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D012243:Rhodopsin; D013329:Structure-Activity Relationship
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D000577:Amides; D011804:Quinolines; D012243:Rhodopsin