Click-based synthesis of triazolobithiazole ΔF508-CFTR correctors for cystic fibrosis

Copper catalyzed azide-alkyne cycloaddition (CuAAC) chemistry is reported for the construction of previously unknown 5-(1H-1,2,3-triazol-1-yl)-4,5′-bithiazoles from 2-bromo-1-(thiazol-5-yl)ethanones. These novel triazolobithiazoles are shown to have cystic fibrosis (CF) corrector activity and, compa...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2012-09, Vol.20 (17), p.5247-5253
Main Authors: Donald, Michael B., Rodriguez, Kevin X., Shay, Hannah, Phuan, Puay-Wah, Verkman, A.S., Kurth, Mark J.
Format: Article
Language:English
Subjects:
azoles
Biological and medical sciences
catalytic activity
CF corrector
copper
CuAAC
Cystic fibrosis
Cystic Fibrosis - drug therapy
Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
Dose-Response Relationship, Drug
Medical sciences
Molecular Structure
Pharmacology. Drug treatments
Structure-Activity Relationship
synthesis
Thiazoles - chemical synthesis
Thiazoles - chemistry
Thiazoles - pharmacology
Triazoles - chemical synthesis
Triazoles - chemistry
Triazoles - pharmacology
Triazolobithiazole
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Summary:Copper catalyzed azide-alkyne cycloaddition (CuAAC) chemistry is reported for the construction of previously unknown 5-(1H-1,2,3-triazol-1-yl)-4,5′-bithiazoles from 2-bromo-1-(thiazol-5-yl)ethanones. These novel triazolobithiazoles are shown to have cystic fibrosis (CF) corrector activity and, compared to the benchmark bithiazole CF corrector corr-4a, improved logP values (4.5 vs 5.96).
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2012.06.046