2D QSAR Studies on Series of Human Beta-secretase (BACE-1) Inhibitors

Author(s): Daniela Santos Cruz , Marcelo Santos Castilho .

Journal Name: Medicinal Chemistry

Volume 10 , Issue 2 , 2014

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β-secretase (BACE-1) plays a pivotal role in the β-Amyloid plaques formation, which is responsible for progressive cognitive and memory loss commonly found in Alzheimer disease patients. As a consequence, it has been considered as a good target for drug development efforts. Early work focused on the synthesis of peptidomimetics, but poor pharmacokinetics profile prevented advancing lead compounds to clinical trials. As an alternative, aminoimidazoles, aminohydantoins and aminopyridines derivatives that inhibit BACE-1 were designed. Herein we report statistically sound descriptor- based (r2 = 0.87, q2 = 0.85, 6 PCs) and fragment-based (r2 = 0.91, q2 = 0.84, 6 PCs) QSAR models, that show high predictive ability (r2 pred = 0.84, averaged r2 m=0.78) and underscore polar interactions that are important for BACE-1 inhibition.

Keywords: Alzheimer, β-Amyloid, Beta-secretase (BACE-1), 2D-QSAR, Hologram QSAR.

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Article Details

Year: 2014
Page: [162 - 173]
Pages: 12
DOI: 10.2174/15734064113099990002
Price: $58

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