1027556-48-4Relevant academic research and scientific papers
Discovery of 2-phenylamino-imidazo[4,5-h]isoquinolin-9-ones: A new class of inhibitors of lck kinase
Snow, Roger J.,Cardozo, Mario G.,Morwick, Tina M.,Busacca, Carl A.,Dong, Yong,Eckner, Robert J.,Jacober, Stephen,Jakes, Scott,Kapadia, Suresh,Lukas, Susan,Panzenbeck, Maret,Peet, Gregory W.,Peterson, Jeffrey D.,Prokopowicz III, Anthony S.,Sellati, Rosemarie,Tolbert, Robert M.,Tschantz, Matt A.,Moss, Neil
, p. 3394 - 3405 (2007/10/03)
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.
