Aminoimidazoles as potent and selective human β-secretase (BACE1) inhibitors

…, J Erdei, I Gunawan, K Barnes, M Johnson…

Index: Malamas, Michael S.; Erdei, Jim; Gunawan, Iwan; Barnes, Keith; Johnson, Matthew; Yu, Hui; Turner, Jim; Yun, Hu; Wagner, Erik; Fan, Kristi; Olland, Andrea; Bard, Jonathan; Robichaud, Albert J. Journal of Medicinal Chemistry, 2009 , vol. 52, # 20 p. 6314 - 6323

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Citation Number: 108

Abstract

The identification of small molecule aminoimidazoles as potent and selective human β- secretase inhibitors is reported. These analogues demonstrate low nannomolar potency for BACE1 in a FRET assay, exhibit comparable activity in a cell-based (ELISA) assay, and show> 100× selectivity for the other structurally related aspartyl proteases BACE2, cathepsin D, renin, and pepsin. Our design strategy was supported by molecular modeling studies ...