In recent studies, combinations of histone deacetylases (HDACs) inhibitor with kinase inhibitor showed additive and synergistic effects. BRaf V600E as an attractive target in many diseases treatments has been studied extensively. Herein, we present a novel design approach though incorporating the pharmacophores of BRaf V600E inhibitor and HDACs inhibitor in one molecule. Several synthesized compounds exhibited distinct BRaf V600E and HDAC1 inhibitory activities. The representative dual Raf/HDAC inhibitor, 7a, showed better antiproliferative activities against A549 and SK-Mel-2 in cellular assay than SAHA and sorafenib, with IC 50 values of 9.11 µM and 5.40 µM, respectively. This work may lay the foundation for the further development of dual Raf/HDAC inhibitors as potential anticancer agents.

Cu(i)-Catalyzed diastereoselective carboboration of α-alkyl-substituted α,β-unsaturated carboxylic esters to produce β-boryl-α-quaternary carbon esters was developed.

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