A plethora of 6-(hetero)aryl C–C and C–N bonded tacrine analogues has been made accessible by employing palladium mediated (Suzuki–Miyaura, Heck, Sonogashira, Stille and Buchwald) cross-coupling reactions, starting from either halogenated or borylated residues. The successful use of Pd(dppf)Cl₂·CH₂Cl₂ as a common catalytic system in realizing all these otherwise challenging transformations is the highlight of our optimized protocols. The analogues thus synthesized allow the available chemical space around the C-6 of this biologically relevant tacrine core to be explored. The in silico docking studies of the synthesized compounds were carried out against the acetylcholinesterase (AChE) enzyme. The hepatotoxicity studies of these compounds were done against complexes of CYP1A2 and CYP3A4 proteins with known inhibitors like 7,8-benzoflavone and ketoconazole, respectively.