904686-43-7Relevant academic research and scientific papers
Acylguanidines as small-molecule β-secretase inhibitors
Cole, Derek C.,Manas, Eric S.,Stock, Joseph R.,Condon, Jeffrey S.,Jennings, Lee D.,Aulabaugh, Ann,Chopra, Rajiv,Cowling, Rebecca,Ellingboe, John W.,Fan, Kristi Y.,Harrison, Boyd L.,Hu, Yun,Jacobsen, Steve,Jin, Guixan,Lin, Laura,Lovering, Frank E.,Malamas, Michael S.,Stahl, Mark L.,Strand, James,Sukhdeo, Mohani N.,Svenson, Kristine,Turner, M. James,Wagner, Erik,Wu, Junjun,Zhou, Ping,Bard, Jonathan
, p. 6158 - 6161 (2006)
BACE1 is an aspartyl protease responsible for cleaving amyloid precursor protein to liberate Aβ, 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 IC50 = 110 nM).
Amino-pyridines as inhibitors of beta-secretase
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Page/Page column 32-33, (2008/06/13)
The present invention provides an amino-pyridine compound of formula I The present invention also provides methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles.
