Click-based synthesis of triazolobithiazole ΔF508-CFTR correctors for cystic fibrosis.
Donald MB, Rodriguez KX, Shay H, Phuan PW, Verkman AS, Kurth MJ.
Copper catalyzed azide-alkyne cycloaddition (CuAAC) chemistry is reported for the construction of previously unknown 5-(1H-1,2,3-triazol-1-yl)-4,5'-bithiazoles from 2-bromo-1-(thiazol-5-yl)ethanones. These novel triazolobithiazoles are shown to have cystic fibrosis (CF) corrector activity and, compared to the benchmark bithiazole CF corrector corr-4a, improved logP values (4.5 vs 5.96).