<![CDATA[Alzheimer’s disease (AD) remains a major progressive neurodegenerative disorder with limited therapeutic efficacy, primarily targeting acetylcholinesterase (AChE), with significant challenges related to Blood-Brain Barrier (BBB) penetration. This study aimed to perform drug likeness screening, ADMET profiling, and BBB penetration prediction of indoloquinoxaline derivatives as potential CNS-active anti-Alzheimer candidates using SwissADME as the sole computational platform. A total of 36 compounds, comprising 31 indoloquinoxaline derivatives and five reference anti-Alzheimer drugs, were analyzed in silico using five pharmacokinetic filters (Lipinski, Ghose, Veber, Egan, and Muegge), followed by lipophilicity assessment (Consensus LogP range: 2.59–5.39), molecular weight, rotatable bonds, hydrogen bonding, and medicinal chemistry evaluations. All 36 compounds fulfilled Lipinski and Veber criteria with 100% compliance, while Ghose, Egan, and Muegge filters identified 3, 2, and 8 violations, respectively, predominantly attributable to excessive lipophilicity in substituents such as –CF₃ and tert-butyl groups. The investigated compounds exhibited CNS-compatible MW (219.24–400.52 Da), LogP (2.88–4.95 for the majority), and TPSA (30.71–54.50 Ų) profiles. A total of 29 out of 31 synthesized compounds (93.5%) were predicted as BBB-permeant. In addition, all candidates showed zero PAINS alerts and predominantly zero Brenk alerts, indicating favorable medicinal chemistry characteristics and low risk of nonspecific bioassay interference. Several compounds demonstrated physicochemical properties comparable to clinically approved anti-Alzheimer drugs (donepezil, galantamine, rivastigmine), suggesting promising potential for further AChE-targeted CNS drug development.]]>
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