Abstract Thiazolopyrimidines and their derivatives have diverse pharmacological uses. This study aimed to synthesize four new bicyclic benzylidene thiazolo3,2‐ a pyrimidin‐3(2 H )‐one derivatives ( 7a–d ), with yields ranging from 89%–94%. The compounds were analyzed using FT‐IR, ¹H NMR, and ¹ 3 C NMR. In silico molecular docking assessed their interactions with Nicastrin (PDB ID: 7Y5X) and Lp‐PLA2 (PDB ID: 5JAN–4), showing high polarity and flexibility, but some limitations in unsaturation, lipophilicity, size, and solubility. The BOILED‐Egg method indicated that while these compounds cannot cross the blood‐brain barrier, they can be absorbed via the gastrointestinal tract. Online predictions suggest they may have biological activity, with an LD 50 of 2000 mg/kg and a Toxicity Class 4 rating. Molecular docking showed Compound 7c had the highest binding affinity to Nicastrin (XP GScore = −10.780) and the most stable binding through hydrophobic interactions (LipophilicEvdw = −7.293), while Compound 7d had the strongest binding to Lp‐PLA2 (XP GScore = −7.578) with π‐π stacking interactions at A:PHE698. Stability was confirmed in simulations, with both protein‐ligand complexes maintaining stability over time. The pharmacokinetics and properties of these compounds suggest potential as inhibitors of Nicastrin and Lp‐PLA2, making them promising candidates for future therapeutic development.
Hamad et al. (Tue,) studied this question.