Discovery and Characterization of MAPK-activated Protein Kinase-2 Prevention of Activation Inhibitors was written by Cumming, John G.;Debreczeni, Judit E.;Edfeldt, Fredrik;Evertsson, Emma;Harrison, Martin;Holdgate, Geoffrey A.;James, Michael J.;Lamont, Scott G.;Oldham, Keith;Sullivan, Jane E.;Wells, Stuart L.. And the article was included in Journal of Medicinal Chemistry in 2015.Quality Control of 3-Amino-4-methylbenzonitrile This article mentions the following:
Two structurally distinct series of novel, MAPK-activated kinase-2 prevention of activation inhibitors have been discovered by high throughput screening. Preliminary structure-activity relationship (SAR) studies revealed substructural features that influence the selective inhibition of the activation by p38α of the downstream kinase MK2 in preference to an alternative substrate, MSK1. Enzyme kinetics, surface plasmon resonance (SPR), 2D protein NMR, and x-ray crystallog. were used to determine the binding mode and the mol. mechanism of action. The compounds bind competitively to the ATP binding site of p38α but unexpectedly with higher affinity in the p38α-MK2 complex compared with p38α alone. This observation is hypothesized to be the origin of the substrate selectivity. The two lead series identified are suitable for further investigation for their potential to treat chronic inflammatory diseases with improved tolerability over previously studied p38α inhibitors. In the experiment, the researchers used many compounds, for example, 3-Amino-4-methylbenzonitrile (cas: 60710-80-7Quality Control of 3-Amino-4-methylbenzonitrile).
3-Amino-4-methylbenzonitrile (cas: 60710-80-7) belongs to nitriles. The electronic structure of nitriles is very similar to that of an alkyne with the main difference being the presence of a set of lone pair electrons on the nitrogen. Alkyl nitriles are sufficiently acidic to undergo deprotonation of the C-H bond adjacent to the CN group.Strong bases are required, such as lithium diisopropylamide and butyl lithium. The product is referred to as a nitrile anion. Quality Control of 3-Amino-4-methylbenzonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts