A series of N-benzylated (pyrrolidin-2-one)/(imidazolidin-2-one) derivatives were synthesized and evaluated for anti-Alzheimer’s activity. The analogs were designed and synthesized on the basis of lead compound donepezil, which is currently prescribed as a major drug for the management of mild to severe Alzheimer’s disease. Considering the structure activity relationship (SAR) of the lead compound, we first replaced the 5,6-dimethoxy-1-indanone moiety with N-benzylated (pyrrolidin-2-one)/(imidazolidin-2-one) (head) without depriving the key functionality interactions like carbonyl and dimethoxyphenyl and second substituted the spacer linkage (tail) in donepezil. The newly synthesized compounds were characterized by structural conformity and purity using various techniques. The compounds were then subjected to in vivo (behavioral studies) and in vitro (biochemical assays) evaluation using appropriate animal models against the standard drug. Compounds 3-(4-(4-fluorobenzoyl)-piperidin-1-yl)-1-(4-methoxybenzyl)-pyrrolidin-2-one (10b) and 1-(3,4-dimethoxybenzyl)-3-((1-(2-(trifluoromethyl)-benzyl)-piperidin-4-yl)-methyl)-imidazolidin-2-one (18c) displayed an excellent anti-Alzheimer’s profile, while the rest of the compounds showed satisfactory results in comparison to donepezil.

中文翻译：

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作为潜在的抗阿尔茨海默病药物的新型苯甲酰化（吡咯烷-2-酮）/（咪唑啉-2-酮）衍生物：合成和药理研究。

合成了一系列N-苄基化（吡咯烷-2-酮）/（咪唑烷基-2-酮）衍生物，并评估了其抗阿尔茨海默氏病的活性。在铅化合物多奈哌齐的基础上设计和合成类似物，多奈哌齐目前被指定为治疗轻度至重度阿尔茨海默氏病的主要药物。考虑到前导化合物的结构活性关系（SAR），我们首先将N-苄基化的（吡咯烷基-2-酮）/（咪唑啉丁-2-酮）（头）替换为5,6-二甲氧基-1-茚满酮部分（头）剥夺了关键的功能相互作用，如羰基和二甲氧基苯基，然后取代了间隔键（尾）在多奈哌齐。使用各种技术对新合成的化合物进行结构整合和纯度表征。然后使用针对标准药物的适当动物模型对化合物进行体内（行为研究）和体外（生化分析）评估。化合物3-（4-（4-氟苯甲酰基）-哌啶-1-基）-1-（4-甲氧基苄基）-吡咯烷-2-酮（10b）和1-（3,4-二甲氧基苄基）-3-（（ 1-（2-（三氟甲基）-苄基）-哌啶-4-基）-甲基）-咪唑啉酮-2-酮（18c）具有出色的抗阿尔茨海默氏病特征，而其余化合物与多奈哌齐。