Formula: C9H11BrClNOOn September 8, 2016 ,《Application of a Parallel Synthetic Strategy in the Discovery of Biaryl Acyl Sulfonamides as Efficient and Selective NaV1.7 Inhibitors》 was published in Journal of Medicinal Chemistry. The article was written by DiMauro, Erin F.; Altmann, Stephen; Berry, Loren M.; Bregman, Howard; Chakka, Nagasree; Chu-Moyer, Margaret; Bojic, Elma Feric; Foti, Robert S.; Fremeau, Robert; Gao, Hua; Gunaydin, Hakan; Guzman-Perez, Angel; Hall, Brian E.; Huang, Hongbing; Jarosh, Michael; Kornecook, Thomas; Lee, Josie; Ligutti, Joseph; Liu, Dong; Moyer, Bryan D.; Ortuno, Daniel; Rose, Paul E.; Schenkel, Laurie B.; Taborn, Kristin; Wang, Jean; Wang, Yan; Yu, Violeta; Weiss, Matthew M.. The article contains the following contents:
The majority of potent and selective hNaV1.7 inhibitors possess common pharmacophoric features that include a heteroaryl sulfonamide headgroup and a lipophilic aromatic tail group. Recently, reports of similar aromatic tail groups in combination with an acyl sulfonamide headgroup have emerged, with the acyl sulfonamide bestowing levels of selectivity over hNaV1.5 comparable to the heteroaryl sulfonamide. Beginning with com. available carboxylic acids that met selected pharmacophoric requirements in the lipophilic tail, a parallel synthetic approach was applied to rapidly generate the derived acyl sulfonamides. A biaryl acyl sulfonamide hit from this library was elaborated, optimizing for potency and selectivity with attention to physicochem. properties. The resulting novel leads are potent, ligand and lipophilic efficient, and selective over hNaV1.5. Representative lead I demonstrates selectivity over other human NaV isoforms and good pharmacokinetics in rodents. The biaryl acyl sulfonamides reported herein may also offer ADME advantages over known heteroaryl sulfonamide inhibitors. In the experiment, the researchers used 5-Bromo-3-chloro-2-isobutoxypyridine(cas: 1289093-31-7Formula: C9H11BrClNO)
5-Bromo-3-chloro-2-isobutoxypyridine(cas: 1289093-31-7) belongs to pyridine. Pyridine, its benzo and pyridine-based compounds play diverse roles in organic chemistry. As ligands, solvents, and catalysts they facilitate reactions; thus descriptions of these new ligands and their applications abound each year.Formula: C9H11BrClNO