4′-Methyl-4,5′-bithiazole-based correctors of defective ΔF508-CFTR cellular processing

The synthesis and ΔF508-CFTR corrector activity of a 148-member methylbithiazole-based library are reported. Synthetic routes were devised and optimized to generate methylbithiazole analogs in four steps. Corrector potency and efficacy were assayed using epithelial cells expressing human ΔF508-CFTR. These structure–activity data establish that the bithiazole substructure plays a critical function; eight novel methylbithiazole correctors were identified with low micromolar potencies.

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