Figure 1.

(A) Structures of compounds A1–A30 (for compound synthesis, see Supporting Figures S1 and S2); NP, no product formed. (B) Structures of scaffolds B–F for the second-generation compound series. (C) Heat maps representing K_i values of selected first-generation members and the full second-generation series against HDAC1, HDAC6, HDAC8, and HDAC11. The K_i values are calculated using the Cheng–Prusoff equation, from IC₅₀ values determined by at least two individual end point assays, performed in duplicate. See Supporting Figures S4 and S9 for full dose–response curves and Supporting Tables S1 for IC₅₀ and calculated K_i values. NI, no inhibition as determined by <50% inhibition at 5 μM inhibitor; ND, not determined as compound was left out of the series.