Identification of 4‐aryl‐1H‐pyrrole[2,3‐b]pyridine derivatives for the development of new B‐Raf inhibitors |
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Abstract: | During the last years, a significant interest in the identification of new classes of B‐Raf inhibitors has emerged. In this study, which was conceived within an effort that culminated in the recent report of the first dual inhibitors of B‐Raf and Hsp90, we describe the identification of four compounds based on 4‐aryl‐1H‐pyrrole[2,3‐b]pyridine scaffold as interesting starting points for the development of new B‐Raf inhibitors. Structure–activity relationships and predicted binding modes are discussed. Moreover, the novelty of the newly identified structures with respect to currently known B‐Raf inhibitors was assessed through a ligand‐based dissimilarity assessment. Finally, structural modifications with the potential ability to improve the activity toward B‐Raf are put forward. |
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Keywords: | B‐Raf docking fingerprints Hsp90 pharmacophore similarity searching virtual screening |
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