1260433-15-5

Upstream product

• 19102-07-9 2,3-dihydrobenzo[b][1,4]dioxine-6-carbonitrile 
• 108-36-1 1,3-dibromobenzene 

Downstream Products

• 1019392-28-9 C₁₅H₁₄BrNO₂ 

Relevant academic research and scientific papers

NOVEL COMPOUNDS FOR TREATMENT OF NEURODEGENERATION ASSOCIATED WITH DISEASES, SUCH AS ALZHEIMER'S DISEASE OR DEMENTIA

The present invention relates to novel compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Downs syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer Disease, memory loss, attention deficit symptoms associated with Alzheimer disease, neurodegeneration associated with diseases such as Alzheimer disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.

Aminoimidazoles as potent and selective human β-secretase (BACE1) inhibitors

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.