5-Phenyl-1,3,4-oxadiazol-2(3H)-ones Are Potent Inhibitors of Notum Carboxylesterase Activity Identified by the Optimization of a Crystallographic Fragment Screening Hit was written by Mahy, William;Willis, Nicky J.;Zhao, Yuguang;Woodward, Hannah L.;Svensson, Fredrik;Sipthorp, James;Vecchia, Luca;Ruza, Reinis R.;Hillier, James;Kjaer, Svend;Frew, Sarah;Monaghan, Amy;Bictash, Magda;Salinas, Patricia C.;Whiting, Paul;Vincent, Jean-Paul;Jones, E. Yvonne;Fish, Paul V.. And the article was included in Journal of Medicinal Chemistry in 2020.COA of Formula: C9H6BrF3O2 This article mentions the following:
Carboxylesterase Notum is a neg. regulator of the Wnt signaling pathway. There is an emerging understanding of the role Notum plays in disease, supporting the need to discover new small-mol. inhibitors. A crystallog. X-ray fragment screen was performed, which identified fragment hit 1,2,3-triazole (I) as an attractive starting point for a structure-based drug design hit-to-lead program. Optimization of I identified oxadiazol-2-one II as a preferred example with properties consistent with drug-like chem. space. Screening of II in a cell-based TCF/LEF reporter gene assay restored the activation of Wnt signaling in the presence of Notum. Mouse pharmacokinetic studies with oral administration of II demonstrated good plasma exposure and partial blood-brain barrier penetration. Significant progress was made in developing fragment hit I into lead II (>600-fold increase in activity), making it suitable as a new chem. tool for exploring the role of Notum-mediated regulation of Wnt signaling. In the experiment, the researchers used many compounds, for example, Methyl 4-bromo-3-(trifluoromethyl)benzoate (cas: 107317-58-8COA of Formula: C9H6BrF3O2).
Methyl 4-bromo-3-(trifluoromethyl)benzoate (cas: 107317-58-8) belongs to organobromine compounds. Most of the natural organobromine compounds are produced by marine organisms, and several brominated metabolites with antibacterial, antitumor, antiviral, and antifungal activity have been isolated from seaweed, sponges, corals, molluscs, and others. One prominent application of synthetic organobromine compounds is the use of polybrominated diphenyl ethers as fire-retardants, and in fact fire-retardant manufacture is currently the major industrial use of the element bromine.COA of Formula: C9H6BrF3O2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary