A new series of novel 4-(substituted-phenyl)-6-phenyl-pyrimidine-2(1H)-ones (4a-f) were synthesized and evaluated for their therapeutic potential as bronchodilators. These compounds were selected based on molecular characteristics and drug-likeness score, ensuring their suitability for oral bioavailability.Microwave-assisted synthesis, a rapid and environmentally friendly technique, was employed to efficiently produce the pyrimidine derivatives with Good yield and purity. The microwave irradiation method offered significant advantages over conventional synthesis, including reduced reaction time and improved product yield of 55% to 85%. This outcome highlights the value of employing green chemistry approaches in drug development.The structures of the derivatives were elucidated by FT-IR, 1H NMR, 13C NMR, and HRMS.All the compounds were given satisfactory reaction yields that represented the efficiency of the employed synthetic route.Clonidineinducedcatalepsy model delayed the onset of catalepsy significantly3(a-f) when compared to an induction control group. In vitro evaluations confirmed that all test substances exhibited both broncho-dilatory and H1-antihistaminic activities, indicating their potential efficacy as anti-asthmatic drugs.Further investigations are underway to elucidate the precise mechanism of action for these compounds and explore other potential isosteres. The promising results from this study support the exploration of pyrimidine derivatives as a novel class of bronchodilators and encourage continued research in the development of effective antiasthmatic medications.