3-(2-Benzyloxyphenyl)isoxazoles and isoxazolines: Synthesis and evaluation as CFTR activators

Robert E. Sammelson, T. Ma, Luis J V Galietta, A. S. Verkman, Mark J. Kurth

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

A novel class of activators for chloride conductance in the cystic fibrosis transmembrane conductance regulator (CFTR) protein has been identified. These 3-(2-benzyloxyphenyl)isoxazoles and 3-(2-benzyloxyphenyl)isoxazolines were synthesized employing the 1,3-dipolar cycloaddition of nitrile oxides with various alkene and alkyne dipolarophiles. Utilizing a fluorescence cell-based assay of halide transport, the best compounds increased CFTR-dependent chloride transport with half-maximal stimulation at 20-50 μM.

Original languageEnglish (US)
Pages (from-to)2509-2512
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume13
Issue number15
DOIs
StatePublished - Aug 4 2003

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Isoxazoles
Cystic Fibrosis Transmembrane Conductance Regulator
Chlorides
Nitriles
Alkynes
Cycloaddition
Cycloaddition Reaction
Alkenes
Oxides
Assays
Fluorescence
Proteins

ASJC Scopus subject areas

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

Cite this

3-(2-Benzyloxyphenyl)isoxazoles and isoxazolines : Synthesis and evaluation as CFTR activators. / Sammelson, Robert E.; Ma, T.; Galietta, Luis J V; Verkman, A. S.; Kurth, Mark J.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 13, No. 15, 04.08.2003, p. 2509-2512.

Research output: Contribution to journalArticle

Sammelson, Robert E. ; Ma, T. ; Galietta, Luis J V ; Verkman, A. S. ; Kurth, Mark J. / 3-(2-Benzyloxyphenyl)isoxazoles and isoxazolines : Synthesis and evaluation as CFTR activators. In: Bioorganic and Medicinal Chemistry Letters. 2003 ; Vol. 13, No. 15. pp. 2509-2512.
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