Efficient synthesis and molecular docking of novel antibacterial pyrimidines and their related fused heterocyclic derivatives

3‐(Benzo[d][1,3]dioxol‐5‐yl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one reacted with each of thiourea and 6‐amino‐2‐thioxo‐2,3‐dihydropyrimidin‐4(1H)‐one to give the corresponding pyrimidine‐2(1H)‐thiones. Then, these compounds reacted with the appropriate hydrazonyl chlorides in dioxane in the presence of triethylamine to afford the corresponding [1,2,4]triazolo[4,3‐a]pyrimidines and their related fused pyridines. Moreover, chalcone was cyclocondensed with 2‐cyanothioacetamide to give pyridine‐2(1H)‐thione and taken as a key synthon to novel 2‐(methylthio)pyridothienopyrimidin‐4(3H)‐one derivative. The above derivative reacted with the appropriate hydrazonyl chlorides in dioxane in the presence of triethylamine to yield the corresponding pyridothieno[3,2‐d][1,2,4]triazolo[4,3‐a]pyrimidines. Study of the in vitro antimicrobial activities of the newly pyrimidines were performed. Pyridothienopyrimidine 24a showed the highest inhibitory activity against all bacteria with MIC values of 3.9, 7.81, 7.81, and 15.62 μg/mL, respectively, against Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Streptococcus mutans, respectively, as compared to reference drugs. Molecular docking was studied to predict of the optimized conformation of pyrimidines as active ligands against the Escherichia coli alkaline phosphatase. The structures of the hybrid molecules were elucidated by IR, Mass, 1H NMR, and 13C NMR spectra as well as elemental analyses.