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 ...