Design,synthesis and biological evaluation of 4-piperazinyl-containing Chidamide derivatives as HDACs inhibitors

The synthesis and biological evaluation of a variety of 4-piperazinyl-containing Chidamide derivatives is described. Some of these compounds were shown to inhibit HDAC1 with IC₅₀ values below micromolar range, and inhibited proliferation of several human cancer cells, not possessing toxicity to human normal cells and hERG K⁺ ion channels. Compound 9g, proved to be the most potent and efficacious derivative in this series, was orally active in an HCT116 xenograft model in vivo.