| Autor: |
Snow, R. J., Cardozo, M. G., Morwick, T. M., Busacca, C. A., Dong, Y., Eckner, R. J., Jacober, S., Jakes, S., Kapadia, S., Lukas, S., Panzenbeck, M., Peet, G. W., Peterson, J. D., Prokopowicz, A. S., III, Sellati, R., Tolbert, R. M., Tschantz, M. A., Moss, N. |
| Zdroj: |
Journal of Medicinal Chemistry; August 2002, Vol. 45 Issue: 16 p3394-3405, 12p |
| Abstrakt: |
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 converting 1 to the imidazo[4,5-h]isoquinolin-9-one (20), resulting in an 18-fold improvement in potency against lck and a 50-fold increase in potency in a cellular assay. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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