905971-91-7Relevant academic research and scientific papers
Acylguanidine inhibitors of β-secretase: Optimization of the pyrrole ring substituents extending into the S1′ substrate binding pocket
Jennings, Lee D.,Cole, Derek C.,Stock, Joseph R.,Sukhdeo, Mohani N.,Ellingboe, John W.,Cowling, Rebecca,Jin, Guixian,Manas, Eric S.,Fan, Kristi Y.,Malamas, Michael S.,Harrison, Boyd L.,Jacobsen, Steve,Chopra, Rajiv,Lohse, Peter A.,Moore, William J.,O'Donnell, Mary-Margaret,Hu, Yun,Robichaud, Albert J.,Turner, M. James,Wagner, Erik,Bard, Jonathan
, p. 767 - 771 (2008/09/17)
The proteolytic enzyme β-secretase (BACE-1) produces amyloid β (Aβ) peptide, the primary constituent of neurofibrillary plaques, implicated in Alzheimer's disease, by cleavage of the amyloid precursor protein. A small molecule inhibitor of BACE-1, (diamin
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 (2007/10/03)
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).
