4′-Methyl-4, 5′-bithiazole-based correctors of defective ΔF508-CFTR cellular processing
CL Yoo, GJ Yu, B Yang, LI Robins, AS Verkman… - Bioorganic & medicinal …, 2008 - Elsevier
CL Yoo, GJ Yu, B Yang, LI Robins, AS Verkman, MJ Kurth
Bioorganic & medicinal chemistry letters, 2008•ElsevierThe 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.
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.
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.
Elsevier