Discovery of 2-phenylamino-imidazo[4,5-h]isoquinolin-9-ones: a new class of inhibitors of lck kinase.

@article{Snow2002DiscoveryO2,
  title={Discovery of 2-phenylamino-imidazo[4,5-h]isoquinolin-9-ones: a new class of inhibitors of lck kinase.},
  author={Roger J. Snow and Mario G. Cardozo and Tina M. Morwick and Carl A. Busacca and Yong Dong and Robert J. Eckner and Stephen P. Jacober and Scott Jakes and Suresh R. Kapadia and Susan M. Lukas and Maret J Panzenbeck and Gregory W Peet and Jeffrey D. Peterson and Anthony S Prokopowicz and Rosemarie H Sellati and Robert M Tolbert and Matt A Tschantz and Neil Moss},
  journal={Journal of medicinal chemistry},
  year={2002},
  volume={45 16},
  pages={3394-405}
}
An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to understand how 1 binds to a related kinase, hck. These results suggested that removing the gem-dimethyl group and flattening the ring would enhance activity. This was realized by… CONTINUE READING