Compounds 5g and 7 emerged as the most promising candidates, approaching the optimal LLE threshold. From a metabolic stability perspective, 5i and 5m exhibited high CLint and short t1/2, suggesting rapid metabolism and potential challenges in maintaining therapeutic plasma concentrations. In contrast, derivative 5e, bearing a pyrimidine ring, displayed greater metabolic stability, highlighting the influence of another nitrogen atom in the ring on reducing metabolic liability.