A number of 5-oxo-pyrazolo[1,5-c]quinazolines (series B-1), bearing at position-2 the claimed (hetero)aryl moiety (compounds 1–8) but also a carboxylate group (9–14), were designed as hA 3 AR antagonists. This study produced some interesting compounds endowed with good hA 3 receptor affinity and high selectivity, being totally inactive at all the other AR subtypes. In contrast, the corresponding 5-ammino derivatives (series B-2) do not bind or bind with very low affinity at the hA 3 AR, the only exception being the 5-N-benzoyl compound 19 that shows a hA 3 K i value in the high μ-molar range. Evaluation of the synthetic intermediates led to the identification of some 5(3)-(2-aminophenyl)-3(5)-(hetero)arylpyrazoles 20–24 with modest affinity but high selectivity toward the hA 3 AR subtype. Molecular docking of the herein reported tricyclic and simplified derivatives was carried out to depict their hypothetical binding mode to our model of hA 3 receptor.