| Literature DB >> 17034121 |
Derek C Cole1, Eric S Manas, Joseph R Stock, Jeffrey S Condon, Lee D Jennings, Ann Aulabaugh, Rajiv Chopra, Rebecca Cowling, John W Ellingboe, Kristi Y Fan, Boyd L Harrison, Yun Hu, Steve Jacobsen, Guixan Jin, Laura Lin, Frank E Lovering, Michael S Malamas, Mark L Stahl, James Strand, Mohani N Sukhdeo, Kristine Svenson, M James Turner, Erik Wagner, Junjun Wu, Ping Zhou, Jonathan Bard.
Abstract
BACE1 is an aspartyl protease responsible for cleaving amyloid precursor protein to liberate Abeta, which aggregates leading to plaque deposits implicated in Alzheimer's disease. We have identified small-molecule acylguanidine inhibitors of BACE1. Crystallographic studies show that these compounds form unique hydrogen-bonding interactions with the catalytic site aspartic acids and stabilize the protein in a flap-open conformation. Structure-based optimization led to the identification of potent analogs, such as 10d (BACE1 IC(50) = 110 nM).Entities:
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Year: 2006 PMID： 17034121 DOI： 10.1021/jm0607451
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446