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Upstream product

• 108-36-1 1,3-dibromobenzene 
• 1120-87-2 4-bromopyridin 
• 766-81-4 3-bromophenylacetylene 
• 2510-22-7 4-pyridylacetylene 
• 591-18-4 1-Bromo-3-iodobenzene 

Downstream Products

• 208182-76-7 1-(3-bromophenyl)-2-pyridin-4-ylethane-1,2-dione 

Relevant academic research and scientific papers

Hydrogenase Mimics in M12L24 Nanospheres to Control Overpotential and Activity in Proton-Reduction Catalysis

Hydrogenase enzymes are excellent proton reduction catalysts and therefore provide clear blueprints for the development of nature-inspired synthetic analogues. Mimicking their catalytic center is straightforward but mimicking the protein matrix around the active site and all its functions remains challenging. Synthetic models lack this precisely controlled second coordination sphere that provides substrate preorganization and catalyst stability and, as a result, their performances are far from those of the natural enzyme. In this contribution, we report a strategy to easily introduce a specific yet customizable second coordination sphere around synthetic hydrogenase models by encapsulation inside M12L24 cages and, at the same time, create a proton-rich nano-environment by co-encapsulation of ammonium salts, effectively providing substrate preorganization and intermediates stabilization. We show that catalyst encapsulation in these nanocages reduces the catalytic overpotential for proton reduction by 250 mV as compared to the uncaged catalyst, while the proton-rich nano-environment created around the catalyst ensures that high catalytic rates are maintained.

Di-substituted pyridinyl aminohydantoins as potent and highly selective human β-secretase (BACE1) inhibitors

The identification of highly selective small molecule di-substituted pyridinyl aminohydantoins as β-secretase inhibitors is reported. The more potent and selective analogs demonstrate low nanomolar potency for the BACE1 enzyme as measured in a FRET assay, and exhibit comparable activity in a cell-based (ELISA) assay. In addition, these pyridine-aminohydantoins are highly selectivity (>500×) against the other structurally related aspartyl proteases BACE2, cathepsin D, pepsin and renin. Our design strategy followed a traditional SAR approach and was supported by molecular modeling studies based on the previously reported aminohydantoin 3a. We have taken advantage of the amino acid difference between the BACE1 and BACE2 at the S2′ pocket (BACE1 Pro70 changed to BACE2 Lys86) to build ligands with >500-fold selectivity against BACE2. The addition of large substituents on the targeted ligand at the vicinity of this aberration has generated a steric conflict between the ligand and these two proteins, thus impacting the ligand's affinity and selectivity. These ligands have also shown an exceptional selectivity against cathepsin D (>5000-fold) as well as the other aspartyl proteases mentioned. One of the more potent compounds (S)-39 displayed an IC50 value for BACE1 of 10 nM, and exhibited cellular activity with an EC50 value of 130 nM in the ELISA assay.

Pyridinyl aminohydantoins as small molecule BACE1 inhibitors

A novel class of pyridinyl aminohydantoins was designed and prepared as highly potent BACE1 inhibitors. Compound (S)-4g showed excellent potency with IC50 of 20 nM for BACE1. X-ray crystallography indicated that the interaction between pyridine

Amino-5-(6-membered)heteroarylimidazolone compounds and the use thereof for beta-secretase modulation

The present invention provides a 2-amino-5-heteroaryl-5-phenylimidazolone compound of formula I The present invention also provides methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles