Ultrasonic-assisted Lossen rearrangment of N-phenylsulfonyloxy succinimide: synthesis, and in silico ADME predictions pharmacokinetics, and druglikenes of 3-ureidopropanamide derivatives & pyrimidine-2,4-diol derivative

N-phenylsulfonyloxy succinimide 2 was synthesized in 75% yield and used as a building block in the synthesis of N,N’-disubstituted urea derivatives. Sonication of compound 2 with amines namely propylamine, allylamine, aniline and hydrazine in one-pot reaction vessel at room temperature afforded 3-ureidopropanamide 3–5 & pyrimidine-2,4-diol derivative 6, respectively in 70–84% isolated yield. Synthetic molecules were characterized by use of 1H NMR (500 MHz, 400 MHz), 13C NMR (125 MHz, 100 MHz), and Mass spectrometry. The reactions undergo a base catalyzed Lossen rearrangement ring transformation with simple purification steps. In silico ADME analysis was performed to predict and evaluate the absorpiton, distribution, metabolism, and excretion of the synthesized molecules in terms of pharmacokinetics and drug-likeness. In silico ADME results show that the synthesized molecules are predicted to fulfill Lipinski (Pfizer) rule of five (RO5) and did not violate the RO5 guidelines. Computational analysis of the synthesized molecules 1–6 predicts favorable water solubility and skin permeation (Log Kp value: −6.80 to −8.88 cm/s). Furthermore, the compounds exhibit good pharmacokinetic profiles, a good bioavailability score, and an absence of PAINS structural alerts, suggesting high drug-likeness. In silico molecular docking simulations of the synthesized compounds 2–6 revealed favorable binding affinities with docking scores ranging from −5.643 kcal/mol to −6.791 kcal/mol. These energetic profiles suggest that the synthesized molecules possess significant inhibitory potential against the target proteins. Overall, in silico ADME analysis yielded promising results for key drug-likeness parameters, specifically regarding the predicted interaction of these molecules with biological systems and their pharmacokinetic behaviour in vivo. These promising computational results support further wet ADME validation of the synthesized molecules to assess drug-likeness in future drug research and drug development plans.