70428-92-1Relevant articles and documents
Aminoimidazoles as potent and selective human β-secretase (BACE1) inhibitors
Malamas, Michael S.,Erdei, Jim,Gunawan, Iwan,Barnes, Keith,Johnson, Matthew,Yu, Hui,Turner, Jim,Yun, Hu,Wagner, Erik,Fan, Kristi,Olland, Andrea,Bard, Jonathan,Robichaud, Albert J.
experimental part, p. 6314 - 6323 (2010/03/31)
The identification of small molecule aminoimidazoles as potent and selective human β-secretase inhibitors is reported. These analogues demonstrate low nannomolar potency for BACE1 in a FRET assay, exhibit comparable activity in a cell-based (ELISA) assay, and show>100x selectivity for the other structurally related aspartyl proteases BACE2, cathepsin D, renin, and pepsin. Our design strategy was supported by molecular modeling studies based on the cocrystal structure of the HTS-hit 3 in the BACE1 active site. These strategies enabled us to integrate pyridine and pyrimidine groups on 3 extending deep into the S3 region of the BACE1 binding pocket and enhancing the ligand's potency. Compound (R)-37 displayed an IC50 value for BACE1 of 20 nM, cellular activity of 90 nM, and > 100-fold selectivity over related aspartyl proteases. Acute oral administration of (R)-37 at 30 mg/kg resulted in a significant 71% reduction of plasma Aβ40 measured at the 6 h time point in a Tg2576 mouse model (p 0.001). 2009 American Chemical Society.
Palladium-catalyzed benzylic arylation of N-benzylxanthone imine
Niwa, Takashi,Yorimitsu, Hideki,Oshima, Koichiro
supporting information; experimental part, p. 4689 - 4691 (2009/05/13)
(Chemical Equation Presented) The direct benzylic arylation of N-benzylxanthone imine with aryl chloride proceeds under palladium catalysis, yielding the corresponding coupling product. The product is readily transformed to benzhydrylamine. Taking into consideration that the imine is readily available from benzylic amine, the overall transformation represents a formal cross-coupling reaction of aryl halide with α-aminobenzyl metal.
