Synthesis and Histone Deacetylase Inhibitory Activity of New Benzamide Derivatives

• Published in: Journal of medicinal chemistry Vol. 42; no. 15; pp. 3001 - 3003
• Main Authors: Suzuki, Tsuneji, Ando, Tomoyuki, Tsuchiya, Katsutoshi, Fukazawa, Nobuyuki, Saito, Akiko, Mariko, Yukiyasu, Yamashita, Takashi, Nakanishi, Osamu
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 29.07.1999; Amer Chemical Soc
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; benzamide; Benzamides - chemical synthesis; Benzamides - chemistry; Benzamides - pharmacology; Biological and medical sciences; Chemistry, Medicinal; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; General aspects; histone deacetylase; Histone Deacetylase Inhibitors; Humans; Life Sciences & Biomedicine; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; Science & Technology; Structure-Activity Relationship; Antineoplastic agent; Acyltransferases; Enzyme; Nitrogen heterocycle; Transferases; Enzyme inhibitor; Organic carbamate; Histone acetyltransferase; In vitro; Pyridine derivatives; Amine; Structure activity relation; Six membered ring; Benzamide derivatives; Carboxamide; Aromatic compound; Chemical synthesis; Arylamine
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm980565u

Newly synthesized benzamide derivatives were evaluated for their inhibitory activity against histone deacetylase. The structure of these derivatives was unrelated to the known inhibitors, and IC50 values of the active compounds were in the range of 2−50 μM. Structure−activity relationship on the benzanilide moiety showed that the 2‘-substituent, an amino or hydroxy group, was indispensable for inhibitory activity. Although the electronic influence of the substituent in the anilide moiety showed only a small effect on inhibitory activity, the steric factor in the anilide moiety, especially at positions 3‘and 4‘, played an important role in interaction with the enzyme. Among these benzamide derivatives, MS-275 (1), which showed significant antitumor activity in vivo, has been selected for further investigation.