57891-96-0Relevant academic research and scientific papers
Copper-catalyzed [2+3]-annulation of N-H imines with vinyl azides: Access to polyaryl 2: H -imidazoles
Zhu, Zhongzhi,Lin, Hanze,Liang, Baihui,Huang, Junjie,Liang, Wanyi,Chen, Lu,Huang, Yubing,Chen, Xiuwen,Li, Yibiao
supporting information, p. 5621 - 5624 (2020/06/19)
A practical method for the synthesis of 2H-imidazoles via a [2+3] annulation of N-H imines with vinyl azides using a copper catalyst is developed. In this conversion, environmentally friendly oxygen is used as the sole oxidant and N2 and H2O are the only by-products. The catalytic transformation, operating under mild conditions, is operationally simple and is considered as a readily available catalytic system having good substrate and functional compatibility with high atom-efficiency without the need for additional ligands or additives.
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.
