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.