LAUSR

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 based on lead compound donepezil, which is currently prescribed as a major drug for the management of mild to severe Alzheimer's disease. Considering the SAR of the lead compound, we firstly replaced 5,6-dimethoxy-1-indanone moiety with N-benzylated (pyrrolidin-2-one) / (imidazolidin-2-one) (head) without depriving the key functionalities interactions like carbonyl and dimethoxyphenyl, and secondly substituted the spacer linkage (tail) in donepezil. The newly synthesized compounds 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 excellent anti-Alzheimer's profile while rest of the compounds showed satisfactory results in comparison to donepezil.