All the newly designed compounds were initially screened in silico to predict their peroral and/or CNS availabilities. These properties are crucial considerations in the drug discovery process for potential anti-AD therapeutics and should be assessed prior to synthesis. For this purpose, the in silico pharmacokinetics, drug-likeness, and ADME (absorption, distribution, metabolism, excretion) prediction was applied to compounds 5a-5o and 7 using a web-based tool SwissADME () . We have also applied pan-assay interference compounds (PAINS) analysis according to the Free ADME-Tox Filtering Tool (FAF-Drugs4) program (). THA, 7-MEOTA, 7-PhO-THA, and memantine were used as references with known CNS status and pharmacokinetic profile . Data are presented in Figure , Tables and (Supplementary Information; SI). Radar charts depicted in Figure display the optimal chemical space for oral bioavailability, which is determined by a combination of factors counting lipophilicity (LIPO), size, polarity (POLAR), solubility (INSOLU), saturation (INSATU), and flexibility (FLEX). The pink area represents this optimum range, while the red lines indicate the predicted state for designed compounds . Notably, the calculated parameters for all compounds, except for 5o, fall within the pink area, indicating their potential for high oral bioavailability . In line with these predictions, the BOILED-Egg model (Figure ), which indicates gastrointestinal absorption (GIA) and blood-brain barrier (BBB) penetration, supports these observations. Indeed, compounds revealed favorable absorption and brain distribution, apart from 5g. For the GIA, all compounds also fulfill the drug-likeness criteria according to other pharmacological models defined by pharmaceutical companies like Veber´s (GSK) , Lipinski´s (Pfizer) , Egan´s (Pharmacopeia) , Ghose´s (Amgen) , and Muegge´s (Bayer) (Table ; SI). Given the importance of physicochemical parameters, we have also predicted and calculated the potential CNS availability by applying the so-called blood-brain barrier (BBB) score . assay interference (PAINS) compounds with a negative result. In summary, derivatives 5a-5o, and 7 unambiguously show high predictive peroral bioavailability, BBB permeation, and acceptable pharmacokinetic profiles, making the compounds prospective candidates for investigation under in vitro conditions with potential follow-up in in vivo studies.