| Summary: | As a significant co-activator involved in cell cycle and cell growth, differentiation and development, p300/CBP has shown extraordinary potential target in cancer therapy. Herein we designed new compounds from the lead compound A-485 based on molecular dynamic simulations. A series of new spirocyclic chroman derivatives was prepared, characterized and proven to be a potential treatment of prostate cancer. The most potent compound <b>B16</b> inhibited the proliferation of enzalutamide-resistant 22Rv1 cells with an IC<sub>50</sub> value of 96 nM. Furthermore, compounds <b>B16</b>–<b>P2</b> displayed favorable overall pharmacokinetic profiles, and better tumor growth inhibition than A-485 in an in vivo xenograft model.
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