Di-substituted pyridinyl aminohydantoins as potent and highly selective human β-secretase (BACE1) inhibitors

…, K Fan, R Chopra, A Olland, J Bard, M Pangalos…

Index: Malamas, Michael S.; Barnes, Keith; Johnson, Matthew; Hui, Yu; Zhou, Ping; Turner, Jim; Hu, Yun; Wagner, Erik; Fan, Kristi; Chopra, Rajiv; Olland, Andrea; Bard, Jonathan; Pangalos, Menelas; Reinhart, Peter; Robichaud, Albert J. Bioorganic and Medicinal Chemistry, 2010 , vol. 18, # 2 p. 630 - 639

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Citation Number: 40

Abstract

The identification of highly selective small molecule di-substituted pyridinyl aminohydantoins as β-secretase inhibitors is reported. The more potent and selective analogs demonstrate low nanomolar potency for the BACE1 enzyme as measured in a FRET assay, and exhibit comparable activity in a cell-based (ELISA) assay. In addition, these pyridine- aminohydantoins are highly selectivity (> 500×) against the other structurally related ...