JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Design, synthesis, and biological evaluation of 4-aminopyrimidine or 4,6-diaminopyrimidine derivatives as beta amyloid cleaving enzyme-1 inhibitors.

A series of novel aminopyrimidine and diaminopyrimidine derivatives were designed and optimized to improve their potency and permeability relative to lead compound 1 (IC50  = 37.4 μM), which was discovered in a previous virtual screening. The potency of the optimized compound, 13g (IC50  = 1.4 μM), was 26-fold greater than that of 1 based on a fluorescence resonance energy transfer assay, and a parallel artificial membrane permeability assay suggested that it could pass through the blood-brain barrier. Additionally, several compounds containing selenium showed good potencies and deserve further investigation as anti-Alzheimer's agents.

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