Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors.

@article{Gellibert2004IdentificationO1,
  title={Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors.},
  author={Françoise J Gellibert and James M Woolven and Marie-H{\'e}l{\`e}ne Fouchet and N Binoy Mathews and Helen Goodland and Victoria L H Lovegrove and Alain Laroze and V P Nguyen and St{\'e}phane Sautet and Ruolan Wang and Cheryl A. Janson and W Wendell Smith and Ga{\"e}l Krysa and Val{\'e}rie Boullay and Anne-Charlotte de Gouville and St{\'e}phane Huet and David B Hartley},
  journal={Journal of medicinal chemistry},
  year={2004},
  volume={47 18},
  pages={4494-506}
}
Optimization of the screening hit 1 led to the identification of novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent and selective inhibitors of the transforming growth factor-beta type I receptor, ALK5. Compounds 15 and 19, which inhibited ALK5 autophosphorylation with IC50 = 6 and 4 nM, respectively, showed potent activities in both binding and cellular assays and exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure of 19 in… CONTINUE READING