The search for effective AD treatments remains a major challenge. Despite ongoing efforts to develop disease-modifying therapies that improve patients´ quality of life, progress has been slow. A breakthrough came in 2019 with the approval of sodium oligomannate (GV-971) in China, which acts differently from other treatments by reducing gut dysbiosis, lowering neuroinflammation, and improving cognitive function . More recently, the introduction of amyloid beta monoclonal antibodies, lecanemab, and donanemab, has renewed optimism for AD therapy. However, their effectiveness remains under debate . The MTDL approach offers a promising strategy for developing new drug candidates for AD. Nevertheless, many of these emerging candidates face significant challenges due to insufficient early-stage knowledge in drug design . To support the development of symptomatic AD treatments, we synthesized 16 novel THA-based derivatives, modifying position 7 with various (hetero)aryl groups and incorporating deuterium to improve pharmacokinetic properties, reduce hepatotoxicity, and enhance overall therapeutic potential. Early drug discovery emphasizes careful optimization of physicochemical properties to ensure efficient delivery and therapeutic effectiveness for drug candidates . To this end, we evaluated the physicochemical parameters of the compounds before synthesis and predicted their oral and CNS availability. Most of them fit well to these criteria. Another critical factor, lipophilicity, was established as it influences ADMET properties. Our study confirmed that most compounds exhibited moderate lipophilicity, a little higher compared to THA. In line with the parent drug THA, compounds revealed ChE inhibition. Among the (hetero)aryl-THA derivatives, 5i was the most potent AChE inhibitor, whereas compound 5m demonstrated the highest activity against BChE. The selectivity index (SI) varied among the compounds, with some derivatives displaying non-selective inhibition pattern.