174606-12-3

Upstream product

• 75-16-1 methylmagnesium bromide 
• 170284-71-6 1-(tert-butoxycarbonyl)-4-(4-chlorobenzyl)piperidine-4-carboxylic acid 
• 142851-03-4 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate 
• 1126-09-6 4-carbethoxypiperidine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 174605-91-5 1-(tert-butoxycarbonyl) 4-ethyl 4-(4-chlorobenzyl)piperidine-4-carboxylate 

Relevant academic research and scientific papers

An integrated biological approach to guide the development of metal-chelating inhibitors of influenza virus PA endonuclease

The influenza virus PA endonuclease, which cleaves capped cellular pre-mRNAs to prime viral mRNA synthesis, is a promising target for novel anti-influenza virus therapeutics. The catalytic center of this enzyme resides in the N-terminal part of PA (PA-Nte

Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors

The biological effects of flavonoids on mammal cells are diverse, ranging from scavenging free radicals and anti-cancer activity to anti-influenza activity. Despite appreciable effort to understand the anti-influenza activity of flavonoids, there is no clear consensus about their precise mode-of-action at a cellular level. Here, we report the development and validation of a screening assay based on AlphaScreen technology and illustrate its application for determination of the inhibitory potency of a large set of polyols against PA N-terminal domain (PA-Nter) of influenza RNA-dependent RNA polymerase featuring endonuclease activity. The most potent inhibitors we identified were luteolin with an IC50 of 72 ± 2 nM and its 8-C-glucoside orientin with an IC50 of 43 ± 2 nM. Submicromolar inhibitors were also evaluated by an in vitro endonuclease activity assay using single-stranded DNA, and the results were in full agreement with data from the competitive AlphaScreen assay. Using X-ray crystallography, we analyzed structures of the PA-Nter in complex with luteolin at 2.0 ? resolution and quambalarine B at 2.5 ? resolution, which clearly revealed the binding pose of these polyols coordinated to two manganese ions in the endonuclease active site. Using two distinct assays along with the structural work, we have presumably identified and characterized the molecular mode-of-action of flavonoids in influenza-infected cells.

DIOXOBUTANOIC ACID DERIVATIVES AS INHIBITORS OF INFLUENZA ENDONUCLEASE

Dioxobutanoic acids substituted with piperidine or similar N-substituted saturated cycloalkyls are found to inhibit the cap-dependent endonuclease of influenza virus. These compounds are useful in the prevention or treatment of infection by influenza viru