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Some drugs used to treat AD are inhibitors of acetylcholinesterase (AChE) and antagonists of N\u2010methyl\u2010D\u2010aspartate receptor (NMDAr), while inhibitors of catechol\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010methyltransferase (COMT) and monoamine oxidase B (MAO\u2010B) are used for PD. Tacrine was the first FDA (Food and Drug Administration) approved drug against AD. Although later withdrawn due to hepatotoxicity, it remains a pivotal scaffold for drug development. Herein, 1295 tacrine derivatives, meant to enhance therapeutic efficacy and safety of the parent compound, were designed through the CADMA\u2010Chem protocol. The chemical space was screened using selection scores based on ADME properties, toxicity, and synthetic accessibility. Two derivatives with the best drug\u2010like behavior were chosen for further investigation. Acid\u2010base constants and reactivity descriptors were estimated for them. 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