Click-based synthesis of triazolobithiazole Δf508-CFTR correctors for cystic fibrosis

Abstract Copper catalyzed azide-alkyne cycloaddition (CuAAC) chemistry is reported for the construction of previously unknown 5-(1 H -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 log  P values (4.5 vs 5.96).