Click-based synthesis of triazolobithiazole Δf508-CFTR correctors for cystic fibrosis

Michael B. Donald, Kevin X. Rodriguez, Hannah Shay, Puay Wah Phuan, A. S. Verkman, Mark J. Kurth

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 log P values (4.5 vs 5.96).

Original languageEnglish (US)
Pages (from-to)5247-5253
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number17
DOIs
StatePublished - Sep 1 2012

Fingerprint

Alkynes
Azides
Cycloaddition
Cystic Fibrosis
Copper
Benchmarking
Cycloaddition Reaction

Keywords

  • CF corrector
  • CuAAC
  • Cystic fibrosis
  • Triazolobithiazole

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Donald, M. B., Rodriguez, K. X., Shay, H., Phuan, P. W., Verkman, A. S., & Kurth, M. J. (2012). Click-based synthesis of triazolobithiazole Δf508-CFTR correctors for cystic fibrosis. Bioorganic and Medicinal Chemistry, 20(17), 5247-5253. https://doi.org/10.1016/j.bmc.2012.06.046

Click-based synthesis of triazolobithiazole Δf508-CFTR correctors for cystic fibrosis. / Donald, Michael B.; Rodriguez, Kevin X.; Shay, Hannah; Phuan, Puay Wah; Verkman, A. S.; Kurth, Mark J.

In: Bioorganic and Medicinal Chemistry, Vol. 20, No. 17, 01.09.2012, p. 5247-5253.

Research output: Contribution to journalArticle

Donald, MB, Rodriguez, KX, Shay, H, Phuan, PW, Verkman, AS & Kurth, MJ 2012, 'Click-based synthesis of triazolobithiazole Δf508-CFTR correctors for cystic fibrosis', Bioorganic and Medicinal Chemistry, vol. 20, no. 17, pp. 5247-5253. https://doi.org/10.1016/j.bmc.2012.06.046
Donald, Michael B. ; Rodriguez, Kevin X. ; Shay, Hannah ; Phuan, Puay Wah ; Verkman, A. S. ; Kurth, Mark J. / Click-based synthesis of triazolobithiazole Δf508-CFTR correctors for cystic fibrosis. In: Bioorganic and Medicinal Chemistry. 2012 ; Vol. 20, No. 17. pp. 5247-5253.
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