The discovery of substituted 4-(3-hydroxyanilino)-quinolines as potent RET kinase inhibitors.

Abstract Substituted 4-(3-hydroxyanilino)-quinoline compounds, initially identified as small-molecule inhibitors of src family kinases, have been evaluated as potential inhibitors of RET kinase. Three compounds, 38 , 31 , and 40 , had K i ’s of 3, 25, and 50 nM in an in vitro kinase assay; while a cell based kinase assay showed K i ’s of 300, 100, and 45 nM, respectively. These compounds represent potential new leads for the treatment of medullary and papillary thyroid cancer.