Aryl and Arylalkyl Substituted 3-Hydroxypyridin-2(1H)-ones: Synthesis and Evaluation as Inhibitors of Influenza A Endonuclease was written by Sagong, Hye Yeon;Bauman, Joseph D.;Nogales, Aitor;Martinez-Sobrido, Luis;Arnold, Eddy;LaVoie, Edmond J.. And the article was included in ChemMedChem in 2019.Synthetic Route of C5H4BrNO2 This article mentions the following:
Seasonal influenza infections are associated with an estimated 250,00-500,000 deaths annually. Resistance to the antiviral M2 ion-channel inhibitors has largely invalidated their clin. utility. Resistance to neuraminidase inhibitors has also been observed in several influenza A virus (IAV) strains. These data have prompted research on inhibitors that target the cap-snatching endonuclease activity of the polymerase acidic protein (PA). Baloxavir marboxil (Xofluza), recently approved for clin. use, inhibits cap-snatching endonuclease. Resistance to Xofluza has been reported in both in vitro systems and in the clinic. An x-ray crystallog. screening campaign of a fragment library targeting IAV endonuclease identified 5-chloro-3-hydroxypyridin-2(1H)-one as a bimetal chelating agent at the active site. We have reported the structure-activity relationships for 3-hydroxypyridin-2(1H)-ones and 3-hydroxyquinolin-2(1H)-ones as endonuclease inhibitors. These studies identified two distinct binding modes associated with inhibition of this enzyme that are influenced by the presence of substituents at the 5- and 6-positions of 3-hydroxypyridin-2(1H)-ones. Herein we report the structure-activity relationships associated with various para-substituted 5-Ph derivatives of 6-(p-fluorophenyl)-3-hydroxypyridin-2(1H)-ones (I) and the effect of using naphthyl, benzyl, and naphthylmethyl groups as alternatives to the p-fluorophenyl substituent on their activity as endonuclease inhibitors. In the experiment, the researchers used many compounds, for example, 5-Bromopyridine-2,3-diol (cas: 34206-49-0Synthetic Route of C5H4BrNO2).
5-Bromopyridine-2,3-diol (cas: 34206-49-0) belongs to pyridine derivatives. Pyridine has a conjugated system of six π electrons that are delocalized over the ring. The molecule is planar and, thus, follows the Hückel criteria for aromatic systems. Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, nicotinic acid (vitamin B3) occurs in some bacteria, fungi, and mammals.Synthetic Route of C5H4BrNO2