阿尔茨海默病 (AD) 是导致痴呆症的原因，占 60-80% 的病例。肿瘤坏死因子-α (TNF-α) 是一种多功能细胞因子，可抵抗感染、炎症和癌症。它已成为针对多种自身免疫性疾病和炎症性疾病的前瞻性治疗靶点。胆碱能不足与阿尔茨海默病有关，并且已经研制出几种胆碱酯酶抑制剂来治疗这种疾病，包括天然产生的抑制剂、合成类似物和混合物。在目前的研究中，我们尝试制备的化合物也可能支持发现和开发新型治疗和预防阿尔茨海默病的药物，使用四氧化锰纳米颗粒（Mn3O4-NPs）作为催化剂，生成具有优异反应条件的化合物。当 4-氰基苯甲醛、氰基乙酸乙酯和硫脲与 Mn3O4-NP 偶联生成化合物 1 时，Biginelli 合成法生成 4-(4-氰基苯基)-6-氧代-2-硫代六氢嘧啶-5-甲腈。这种多组分方法无毒、安全、环保。新方法减少了化学品的使用量并节省了时间。化合物1与碘甲烷、丙烯腈、氯丙酮、氯乙酸乙酯、氯乙酸/苯甲醛反应，合成的各化合物均与TNF-α转换酶对接。这些化合物还可能支持阿尔茨海默病的新型治疗和预防药物的发现和开发。所生产的大多数化合物都表现出药代动力学特征，使其成为阿尔茨海默病治疗的潜在有吸引力的候选药物。© 2024。作者。

Alzheimer disease (AD) is the cause of dementia and accounts for 60-80% cases. Tumor Necrosis Factor-alpha (TNF-α) is a multifunctional cytokine that provides resistance to infections, inflammation, and cancer. It developed as a prospective therapeutic target against multiple autoimmune and inflammatory disorders. Cholinergic insufficiency is linked to Alzheimer's disease, and several cholinesterase inhibitors have been created to treat it, including naturally produced inhibitors, synthetic analogs, and hybrids. In the current study, we tried to prepared compounds may also support the discovery and development of novel therapeutic and preventative drugs for Alzheimer's using manganese tetroxide nanoparticles (Mn3O4-NPs) as a catalyst to generate compounds with excellent reaction conditions. The Biginelli synthesis yields 4-(4-cyanophenyl)-6-oxo-2-thioxohexahydropyrimidine-5-carbonitrile when the 4-cyanobenzaldehyde, ethyl cyanoacetate, and thiourea were coupled with Mn3O4-NPs to produce compound 1. This multi-component method is non-toxic, safe, and environmentally friendly. The new approach reduced the amount of chemicals used and preserved time. Compound 1 underwent reactions with methyl iodide, acrylonitrile, chloroacetone, ethyl chloroacetate, and chloroacetic acid/benzaldehyde, each of the synthetized compounds was docked with TNF-α converting enzyme. These compounds may also support the discovery and development of novel therapeutic and preventative drugs for Alzheimer's disease. The majority of the produced compounds demonstrated pharmacokinetic features, making them potentially attractive therapeutic candidates for Alzheimer's disease treatment.© 2024. The Author(s).