Herein, in the design of novel potential drugs for AD, we extended our attention to agents, which are attached directly to the primary THA structure (Figure ). We introduce alternative groups, including aromatic heterocycles or aromatic rings at position 7, as C-C bonds are known to be more resistant to enzymatic cleavage, leading to increased metabolic stability of drugs . In contrast, C-O bonds are more susceptible to hydrolysis and oxidation by metabolic enzymes, potentially leading to rapid drug degradation and elimination . In addition to (hetero)aryl substitution, we also explored the incorporation of deuterium, a bioisostere of hydrogen, at the same position. The C-D bond is stronger than the C-H bond due to the kinetic isotope effect, which can modify the metabolic pathway or reduce the hydroxylation rate. This alteration can decrease the formation of toxic metabolites, thereby enhancing the compound´s safety profile .