On January 31, 2020, Dato, Florian M.; Neudoerfl, Joerg-Martin; Guetschow, Michael; Goldfuss, Bernd; Pietsch, Markus published an article.Reference of 2-(2-Bromoethyl)isoindoline-1,3-dione The title of the article was ω-Quinazolinonylalkyl aryl ureas as reversible inhibitors of monoacylglycerol lipase. And the article contained the following:
The serine hydrolase monoacylglycerol lipase (MAGL) is involved in a plethora of pathol. conditions, in particular pain and inflammation, various types of cancer, metabolic, neurol. and cardiovascular disorders, and is therefore a promising target for drug development. Although a large number of irreversible-acting MAGL inhibitors have been discovered over the past years, there are only few compounds known so far which inhibit the enzyme in a reversible manner. Therefore, much effort is put into the development of novel chem. entities showing reversible inhibitory behavior, which is thought to cause less undesired side effects. To explore a wide range of chem. structures as MAGL binders, we have applied a virtual screening approach by docking small mols. into the crystal structure of human MAGL (hMAGL) and envisaged a library of 45 selected compounds which were then synthesized. Biochem. investigations included the determination of the inhibitory potency on hMAGL and two related hydrolases, i.e. human fatty acid amide hydrolase (hFAAH) and murine cholesterol esterase (mCEase). The most promising candidates from theses analyses, i.e. three ω-quinazolinonylalkyl aryl ureas bearing alkyl spacers of three to five methylene groups, exhibited IC50 values of 20-41μM and reversible, detergent-insensitive behavior towards hMAGL. Among these compounds, the inhibitor 1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-(4-oxo-3,4-dihydroquinazolin-2-yl)butyl)urea (96) was selected for further kinetic characterization, yielding a dissociation constant Ki = 15.4μM and a mixed-type inhibition with a pronounced competitive component (α = 8.94). This mode of inhibition was further supported by a docking experiment, which suggested that the inhibitor occupies the substrate binding pocket of hMAGL. The experimental process involved the reaction of 2-(2-Bromoethyl)isoindoline-1,3-dione(cas: 574-98-1).Reference of 2-(2-Bromoethyl)isoindoline-1,3-dione
The Article related to quinazolinonylalkyl aryl urea inhibitor monoacylglycerol lipase, cholesterol esterase, enzyme kinetics, fatty acid amide hydrolase, inhibitors, monoacylglycerol lipase, promiscuous inhibition, serine hydrolases and other aspects.Reference of 2-(2-Bromoethyl)isoindoline-1,3-dione
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary