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 microM.
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 & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 13:15(2003), p. 2509-12.
3-(2-Benzyloxyphenyl)isoxazoles and isoxazolines: synthesis and evaluation as CFTR activators
Galietta, Luis J V;
2003
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 microM.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
