ArticleJournal of medicinal chemistry2010
Pyrazolylthiazole as DeltaF508-cystic fibrosis transmembrane conductance regulator correctors with improved hydrophilicity compared to bithiazoles.
Article in Journal of medicinal chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Ligand-based virtual-screening identified a novel CFTR ligand which improves the defective cell surface expression of misfolded ABC transporters.Frontiers in pharmacology · 2024Article
- Molecular Docking and QSAR Studies as Computational Tools Exploring the Rescue Ability of F508del CFTR Correctors.International journal of molecular sciences · 2020Article
- Innovative Therapies for Cystic Fibrosis: The Road from Treatment to Cure.Molecular diagnosis & therapy · 2019Review
- Molecular basis of cystic fibrosis: from bench to bedside.Annals of translational medicine · 2018Review
- Potentiation of ΔF508- and G551D-CFTR-Mediated Cl- Current by Novel Hydroxypyrazolines.PloS one · 2016Article
- ΔF508-CFTR correctors: synthesis and evaluation of thiazole-tethered imidazolones, oxazoles, oxadiazoles, and thiadiazoles.Bioorganic & medicinal chemistry letters · 2014Article
- Cystic fibrosis transmembrane regulator correctors and potentiators.Cold Spring Harbor perspectives in medicine · 2013Review
- Identification of inhibitors against interaction between pro-inflammatory sPLA2-IIA protein and integrin αvβ3.Bioorganic & medicinal chemistry letters · 2013Article
- Click-based synthesis of triazolobithiazole ΔF508-CFTR correctors for cystic fibrosis.Bioorganic & medicinal chemistry · 2012Article
- Structure-activity relationships of cyanoquinolines with corrector-potentiator activity in ΔF508 cystic fibrosis transmembrane conductance regulator protein.Journal of medicinal chemistry · 2012Article
- CFTR: folding, misfolding and correcting the ΔF508 conformational defect.Trends in molecular medicine · 2012Review
- Functional fluorescently labeled bithiazole ΔF508-CFTR corrector imaged in whole body slices in mice.Bioconjugate chemistry · 2011Article
- Cyanoquinolines with independent corrector and potentiator activities restore ΔPhe508-cystic fibrosis transmembrane conductance regulator chloride channel function in cystic fibrosis.Molecular pharmacology · 2011Article
- Potential Agents for Treating Cystic Fibrosis: Cyclic Tetrapeptides that Restore Trafficking and Activity of ΔF508-CFTR.ACS medicinal chemistry letters · 2011Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Deletion of phenylalanine residue 508 (DeltaF508) in the cystic fibrosis (CF) transmembrane conductance regulator protein (CFTR) is a major cause of CF. Small molecule "correctors" of defective DeltaF508-CFTR cellular processing hold promise for CF therapy. We previously identified and characterized bithiazole CF corrector 1 and s-cis-locked bithiazole 2. Herein, we report the regiodivergent synthesis of Ngamma and Nbeta isomers of thiazole-tethered pyrazoles with improved hydrophilicity compared to bithiazoles. We synthesized a focused library of 54 pyrazolylthiazoles 3, which included examples of both regioisomers 4 and 5. The thiazole-tethered pyrazoles allowed incorporation of property-modulating functionality on the pyrazole ring (ester, acid, and amide) while retaining DeltaF508-CFTR corrector activity (EC(50)) of under 1 microM. The most active pyrazolylthiazole (14h) has an experimentally determined log P of 4.1, which is 1.2 log units lower than bithiazole CF corrector 1.
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