Alzheimer’s Disease (AD) is the most frequent illness and cause of death amongst the age related-neurodegenerative disorders. The Alzheimer’s Disease International (ADI) reported in 2019 that over 50 million people were living with dementia in the world and this number could potentially be around 152 million by 2050.5-hydroxtryptamine subtype 6 receptor (5-HT₆R) has been identified as a potential anti-amnesic drug target and therefore, the administration of 5-HT₆R antagonists can likely mitigate the memory loss and intellectual deterioration associated with AD. Herein, computational tools were applied to design new 5-HT₆ antagonists and their biological activity values were predicted by our QSAR model obtained from Artificial Neural Networks (ANN). The proposed compounds here from the QSAR-ANN model presented significant biological activity values and some of them have achieved pK_i above 9.00. Furthermore, our results suggest that the presence of halogen atoms (especially bromine) linked to the aromatic ring at para-position (HYD) contribute considerably to the increase of the biological activity values while bulky groups in the PI position do not culminate with the increase antagonist activity of compounds here analyzed. Finally, the ADME/Tox profile as well as the synthetic accessibility of new proposed compounds qualify them to go on further with experimental procedures and thenceforward their antagonist effects can be confirmed.

在与年龄有关的神经退行性疾病中，阿尔茨海默氏病（AD）是最常见的疾病和死亡原因。国际老年痴呆症（ADI）在2019年报告称，全世界有超过5000万人患有痴呆症，根据2050.5-羟色胺₆型亚型受体（5-HT ₆ R）的鉴定，该数字可能约为1.52亿。潜在的抗记忆删除药物靶标，因此，使用5-HT ₆ R拮抗剂可以减轻与AD相关的记忆力丧失和智力下降。本文中，计算工具被用于设计新的5-HT ₆通过从人工神经网络（ANN）获得的QSAR模型预测了其拮抗剂及其生物学活性值。QSAR-ANN模型在此提出的化合物显示出显着的生物学活性值，其中一些化合物的pK _i高于9.00。此外，我们的结果表明，卤素原子的存在（特别是溴）与该芳环在对位位置（HYD）极大地促进了生物活性值的增加，而PI位置上的庞大基团并未因此处分析的化合物的拮抗活性增加而达到顶峰。最后，ADME / Tox谱以及新拟议化合物的合成可及性使它们有资格通过实验程序进一步进行研究，因此可以确认其拮抗作用。