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A novel series of pyrazolo[3,4-c]isoquinoline derivatives was discovered as B-RafV600E inhibitors through scaffold hopping based on a literature lead PLX4720. Further SAR exploration and optimization led to the discovery of potent B-RafV600E inhibitors with good oral bioavailability in rats and dogs. One of the compounds EBI-907 (13g) demonstrated excellent in vivo efficacy in B-RafV600E dependent...
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