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Discovery and optimization of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1
Keith R Hornberger1, Dan M Berger, Andrew P Crew
1OSI Pharmaceuticals LLC, 1 Bioscience Park Drive, Farmingdale, NY 11735, USA. keith.hornberger@boehringer-ingelheim.com
Abstract:
The discovery and potency optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. Micromolar hits taken from high-throughput screening were optimized for biochemical and cellular mechanistic potency to ~10nM, as exemplified by compound 12az. Application of structure-based drug design aided by co-crystal structures of TAK1 with inhibitors significantly shortened the number of iterations required for the optimization.
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