title: 4'-Methyl-4,5'-bithiazole-based correctors of defective delta F508-CFTR cellular processing.
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.
authors.affiliation: Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Choong Leol
authors.initials: CL
authors.lastname: Yoo
authors.forename: Gui Jun
authors.initials: GJ
authors.lastname: Yu
authors.forename: Baoxue
authors.initials: B
authors.lastname: Yang
authors.forename: Lori I
authors.initials: LI
authors.lastname: Robins
authors.forename: A S
authors.initials: AS
authors.lastname: Verkman
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Kurth
mesh_terms: D000586:Amination; D002460:Cell Line; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D013844:Thiazoles; D019005:Cystic Fibrosis Transmembrane Conductance Regulator