Application In Synthesis of 2-Pyridinylboronic acidIn 2021 ,《Scaffold-Hopping Strategy on a Series of Proteasome Inhibitors Led to a Preclinical Candidate for the Treatment of Visceral Leishmaniasis》 appeared in Journal of Medicinal Chemistry. The author of the article were Thomas, Michael; Brand, Stephen; De Rycker, Manu; Zuccotto, Fabio; Lukac, Iva; Dodd, Peter G.; Ko, Eun-Jung; Manthri, Sujatha; McGonagle, Kate; Osuna-Cabello, Maria; Riley, Jennifer; Pont, Caterina; Simeons, Frederick; Stojanovski, Laste; Thomas, John; Thompson, Stephen; Viayna, Elisabet; Fiandor, Jose M.; Martin, Julio; Wyatt, Paul G.; Miles, Timothy J.; Read, Kevin D.; Marco, Maria; Gilbert, Ian H.. The article conveys some information:
There is an urgent need for new treatments for visceral leishmaniasis (VL), a parasitic infection which impacts heavily large areas of East Africa, Asia, and South America. We previously reported on the discovery of GSK3494245/DDD01305143 (1) as a preclin. candidate for VL and, herein, we report on the medicinal chem. program that led to its identification. A hit from a phenotypic screen was optimized to give a compound with in vivo efficacy, which was hampered by poor solubility and genotoxicity. The work on the original scaffold failed to lead to developable compounds, so an extensive scaffold-hopping exercise involving medicinal chem. design, in silico profiling, and subsequent synthesis was utilized, leading to the preclin. candidate. The compound was shown to act via proteasome inhibition, and we report on the modeling of different scaffolds into a cryo-EM structure and the impact this has on our understanding of the series’ structure-activity relationships. In the experiment, the researchers used many compounds, for example, 2-Pyridinylboronic acid(cas: 197958-29-5Application In Synthesis of 2-Pyridinylboronic acid)
2-Pyridinylboronic acid(cas: 197958-29-5) belongs to pyridine. The basicity and metallophilic high donor number of these π-deficient systems has long favored them as ligands in metal catalysis. The last decade saw pyridine assume a stronger role as functional group for directed C–H oxidation/activation.Application In Synthesis of 2-Pyridinylboronic acid