In:
Chemical Biology & Drug Design, Wiley, Vol. 88, No. 5 ( 2016-11), p. 710-723
Abstract:
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 IC 50 = 20 n m ; AC hE IC 50 = 2.2 μ m ) and was able to inhibit amyloid aggregation (40% inhibition at 25 μ m ). Compounds 9e (6‐chloro‐ N‐ (3,4‐dimethoxybenzyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine, AC hE IC 50 = 0.8 μ m ; BuChE IC 50 = 1.4 μ m ; Aβ‐aggregation inhibition = 75.7% inhibition at 25 μ m ) and 11b (6‐chloro‐ N‐ (3,4‐dimethoxyphenethyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine, AC hE IC 50 = 0.6 μ m ; BuChE IC 50 = 1.9 μ m ; Aβ‐aggregation inhibition = 85.9% inhibition at 25 μ m ) 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 AC hE inhibitor ( IC 50 = 90 n m ). 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.
Type of Medium:
Online Resource
ISSN:
1747-0277
,
1747-0285
DOI:
10.1111/cbdd.2016.88.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2216600-2
SSG:
12
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