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

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 Ki’s of 3, 25, and 50 nM in an in vitro kinase assay; while a cell based kinase assay showed Ki’s of 300, 100, and 45 nM, respectively. These compounds represent potential new leads for the treatment of medullary and papillary thyroid cancer.

Graphical abstractSubstituted 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 Ki values of 3, 25, and 50 nM in an in vitro kinase assay; while a cell based kinase assay showed Ki values of 300, 100, and 45 nM, respectively. These compounds represent potential new leads for the treatment of medullary and papillary thyroid cancer.Figure optionsDownload full-size imageDownload as PowerPoint slide