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

Bioorganic & Medicinal Chemistry Letters
2008.0

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.

Knowledge Graph

Similar Paper

4′-Methyl-4,5′-bithiazole-based correctors of defective ΔF508-CFTR cellular processing
Bioorganic & Medicinal Chemistry Letters 2008.0
Potent s-cis-Locked Bithiazole Correctors of ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator Cellular Processing for Cystic Fibrosis Therapy
Journal of Medicinal Chemistry 2008.0
Pyrazolylthiazole as ΔF508-Cystic Fibrosis Transmembrane Conductance Regulator Correctors with Improved Hydrophilicity Compared to Bithiazoles
Journal of Medicinal Chemistry 2010.0
ΔF508-CFTR correctors: Synthesis and evaluation of thiazole-tethered imidazolones, oxazoles, oxadiazoles, and thiadiazoles
Bioorganic & Medicinal Chemistry Letters 2014.0
Synthesis and structure–activity relationship of aminoarylthiazole derivatives as correctors of the chloride transport defect in cystic fibrosis
European Journal of Medicinal Chemistry 2015.0
Synthesis and biological evaluation of novel thiazole- VX-809 hybrid derivatives as F508del correctors by QSAR-based filtering tools
European Journal of Medicinal Chemistry 2018.0
Cystic Fibrosis: A New Target for 4-Imidazo[2,1-b]thiazole-1,4-dihydropyridines
Journal of Medicinal Chemistry 2011.0
Discovery and SAR of 4-aminopyrrolidine-2-carboxylic acid correctors of CFTR for the treatment of cystic fibrosis
Bioorganic & Medicinal Chemistry Letters 2022.0
Ligand-based design, in silico ADME-Tox filtering, synthesis and biological evaluation to discover new soluble 1,4-DHP-based CFTR activators
European Journal of Medicinal Chemistry 2012.0
Antitumor Benzothiazoles. 14. Synthesis and in Vitro Biological Properties of Fluorinated 2-(4-Aminophenyl)benzothiazoles
Journal of Medicinal Chemistry 2001.0