5782-95-6Relevant academic research and scientific papers
Structure–activity relationship studies of benzyl-, phenethyl-, and pyridyl-substituted tetrahydroacridin-9-amines as multitargeting agents to treat Alzheimer's disease
Osman, Wesseem,Mohamed, Tarek,Sit, Victor Munsing,Vasefi, Maryam S.,Beazely, Michael A.,Rao, Praveen P. N.
, p. 710 - 723 (2016)
A library of substituted tetrahydroacridin-9-amine derivatives were designed, synthesized, and evaluated as dual cholinesterase and amyloid aggregation inhibitors. Compound 8e (N-(3,4-dimethoxybenzyl)-1,2,3,4-tetrahydroacridin-9-amine) was identified as a potent inhibitor of butyrylcholinesterase (BuChE IC50?=?20?nm; AChE IC50?=?2.2?μm) and was able to inhibit amyloid aggregation (40% inhibition at 25?μm). Compounds 9e (6-chloro-N-(3,4-dimethoxybenzyl)-1,2,3,4-tetrahydroacridin-9-amine, AChE IC50?=?0.8?μm; BuChE IC50?=?1.4?μm; Aβ-aggregation inhibition?=?75.7% inhibition at 25?μm) and 11b (6-chloro-N-(3,4-dimethoxyphenethyl)-1,2,3,4-tetrahydroacridin-9-amine, AChE IC50?=?0.6?μm; BuChE IC50?=?1.9?μm; Aβ-aggregation inhibition?=?85.9% inhibition at 25?μm) were identified as the best compounds with dual cholinesterase and amyloid aggregation inhibition. The picolylamine-substituted compound 12c (6-chloro-N-(pyridin-2-ylmethyl)-1,2,3,4-tetrahydroacridin-9-amine) was the most potent AChE inhibitor (IC50?=?90?nm). These investigations demonstrate the utility of 3,4-dimethoxyphenyl substituent as a novel pharmacophore possessing dual cholinesterase inhibition and anti-Aβ-aggregation properties that can be used in the design and development of small molecules with multitargeting ability to treat Alzheimer's disease.
