Chlamydocin, a cyclic tetrapeptide containing aminoisobutyric acid (Aib), l-phenylalanine (l-Phe), d-proline (d-Pro), and a unique amino acid l-2-amino-8-oxo-9,10-epoxydecanoic acid, inhibits the histone deacetylases (HDACs), a class of enzymes, which play important roles in regulation of gene expression. Sulfur containing amino acids can also inhibit potently, so zinc ligand, such as sulfhydryl group connected with a linker to the so-called capping group, corresponding to cyclic tetrapeptide framework in case of chlamydocin is supposed to interact with the surface of HDAC molecule. Various changes in amino acid residues in chlamydocin may afford specific inhibitors toward HDAC paralogs. To find out specific inhibitors, we focused on benzene ring of l-Phe in chlamydocin framework to shift to various parts of cyclic tetrapeptide. We prepared and introduced several aromatic amino acids into the cyclic tetrapeptides. By evaluating inhibitory activity of these macrocyclic peptides against HDACs, we could find potent inhibitors by shifting the aromatic ring to the Aib site.