Scheme for the synthesis of T247 and T326.

<p>Reagents and conditions: (a) CuSO₄, sodium ascorbate, EtOH, H₂O, room temp, 65% for <b>T247</b>; 97% for <b>T326</b>.</p

HDAC-Inhibitory Activity of vorinostat (3), compound 1, T247, and T326 ^a.

a<p>Values are means of at least three experiments.</p

Design of triazole-containing HDAC inhibitor candidates.

<p>Design of triazole-containing HDAC inhibitor candidates.</p

Total HDACs activity in the presence of 48 hydroxamates (1 µM).

<p>Total HDACs activity in the presence of 48 hydroxamates (1 µM).</p

Previously reported HDAC3-selective inhibitors 1 and 2.

<p>Previously reported HDAC3-selective inhibitors 1 and 2.</p

Activity of total HDACs in the presence of 59 <i>o</i>-aminoanilides (10 µM).

<p>Activity of total HDACs in the presence of 59 <i>o</i>-aminoanilides (10 µM).</p

Scheme for the synthesis of Ak1–Ak3.

<p>Reagents and conditions: (a) EDCI, HOBt, DMF, room temp, 36–62%.</p

Binding mode of T247.

<p>(A) View of the conformation of <b>T247</b> (tube) docked in the HDAC3 catalytic core. Compound <b>T247</b> was docked into a model based on the crystal structure of HDAC3 (PDB code 4A69) using the Molegro Virtual Docker software package. Residues around <b>T247</b> are displayed as wires. (B) The same view as A. The narrow and long tunnel of the active site is displayed as a green mesh. (C) Schematic diagram of <b>T247</b>-binding to the catalytic site.</p

HDAC3 inhibition in the presence of vorinostat (3), compound 1, and 11 o-aminoanilides at 1 µM and 3 µM.^a

a<p>Values are means of two experiments.</p

Scheme for the synthesis of Az13 and Az14.

<p>Reagents and conditions: (a) NaN₃, DMSO, room temp, 97% for <b>Az13</b>; 64% for <b>Az14</b>.</p