Abstract
The synthesis and Delta F508-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 Delta F508-CFTR. These structure-activity data establish that the bithiazole substructure plays a critical function; eight novel methylbithiazole correctors were identified with low micromolar potencies.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Amination
-
Cell Line
-
Cystic Fibrosis Transmembrane Conductance Regulator / genetics
-
Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
-
Epithelial Cells / drug effects
-
Humans
-
Molecular Structure
-
Structure-Activity Relationship
-
Thiazoles / chemical synthesis
-
Thiazoles / chemistry*
-
Thiazoles / pharmacology*
Substances
-
Thiazoles
-
Cystic Fibrosis Transmembrane Conductance Regulator