Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 1: Quaternary amines was written by Hunt, Thomas;Atherton-Watson, Hazel C.;Axford, Jake;Collingwood, Stephen P.;Coote, Kevin J.;Cox, Brian;Czarnecki, Sarah;Danahay, Henry;Devereux, Nick;Howsham, Catherine;Hunt, Peter;Paddock, Victoria;Paisley, Derek;Young, Alice. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2012.Name: Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate This article mentions the following:
We report the identification of a novel series of human epithelial sodium channel (ENaC) blockers that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. Following a rational design hypothesis a series of quaternary amines were prepared and evaluated for their ability to block ion transport via ENaC in human bronchial epithelial cells (HBECs). Compound 11 has an IC50 of 200 nM and is efficacious in the Guinea-pig tracheal p.d. (TPD) model of ENaC blockade with an ED50 of 44 μg kg-1 at 1 h. As such, pyrazinoyl quaternary amines represent the first examples of a promising new class of human ENaC blockers. In the experiment, the researchers used many compounds, for example, Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (cas: 1458-01-1Name: Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate).
Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (cas: 1458-01-1) belongs to pyrazine derivatives. Pyrazines are volatile compounds that are used in the cosmetic, food, flavor, and fragrance industries. Substituted pyrazines have been found as subunits of multiple synthetically constructed therapeutic agents, as well as several natural products.Name: Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate