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

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

Volume: 10 Issue: 2

Author(s): Daniela Santos Cruz and Marcelo Santos Castilho

Affiliation:

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

Abstract: 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.

Cite this article as:

Cruz Santos Daniela and Castilho Santos Marcelo, 2D QSAR Studies on Series of Human Beta-secretase (BACE-1) Inhibitors, Medicinal Chemistry 2014; 10 (2) . https://dx.doi.org/10.2174/15734064113099990002