Synlett

Isoxazolopyrimidines as Novel ΔF508-CFTR Correctors

GJ Yu, B Yang, AS Verkman, MJ Kurth

Index: Yu, Gui Jun; Yang, Baoxue; Verkman; Kurth, Mark J. Synlett, 2010 , # 7 p. 1063 - 1066

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Citation Number: 2

Abstract

Abstract Using a cell-based high-throughput screen, we identified isoxazolo [5, 4-d] pyrimidines as novel small-molecule correctors of the cystic fibrosis mutant protein ΔF508- CFTR. 22 Isoxazolo [5, 4-d] pyrimidine analogues were synthesized and tested. Synthesis of the key intermediate, 5-amino-3-arylisoxazole-4-carboxamide, was accomplished by nitrile oxide cycloaddition to (2-amino-1-cyano-2-oxoethyl) sodium. Formation of 3-arylisoxazolo ...