892872-44-5Relevant academic research and scientific papers
Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of β-secretase
Congreve, Miles,Aharony, David,Albert, Jeffrey,Callaghan, Owen,Campbell, James,Carr, Robin A. E.,Chessari, Gianni,Cowan, Suzanna,Edwards, Philip D.,Frederickson, Martyn,McMenamin, Rachel,Murray, Christopher W.,Patel, Sahil,Wallis, Nicola
, p. 1124 - 1132 (2007/10/03)
Fragment-based lead discovery has been successfully applied to the aspartyl protease enzyme β-secretase (BACE-1). Fragment hits that contained an aminopyridine motif binding to the two catalytic aspartic acid residues in the active site of the enzyme were the chemical starting points. Structure-based design approaches have led to identification of low micromolar lead compounds that retain these interactions and additionally occupy adjacent hydrophobic pockets of the active site. These leads form two subseries, for which compounds 4 (IC50 = 25 μM) and 6c (IC50 = 24 μM) are representative. In the latter series, further optimization has led to 8a (IC50 = 690 nM).
SUBSTITUTED AMINOPYRIDINES AND USES THEREOF
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Page/Page column 92; 95, (2010/11/08)
This invention relates to novel compounds having the structural formula (I) and to their pharmaceutically acceptable salt, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.
