4-Hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as potent anti-tumor agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 2; pp. 455 - 458
• Main Authors: Hayakawa, Ichiro, Shioya, Rieko, Agatsuma, Toshinori, Furukawa, Hidehiko, Naruto, Shunji, Sugano, Yuichi
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 19.01.2004; Elsevier
• Subjects: Anticancer; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Benzofurans - chemical synthesis; Benzofurans - pharmacology; Biological and medical sciences; Carboxylic Acids - chemical synthesis; Carboxylic Acids - pharmacology; Cell Line, Tumor; Esters; General aspects; Humans; Medical sciences; Pharmacology. Drug treatments; Anticancer; Antineoplastic agent; Human; Benzene derivatives; Cytotoxicity; Oxygen heterocycle; Ketone; In vitro; Cell line; Structure activity relation; Bicyclic compound; Phenols; Aromatic compound; Diether; Chemical synthesis; Tumor cell
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2003.10.039

Based on the structure of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester ( 1), which exhibits selective cytotoxicity against a tumorigenic cell line, (2,4-dimethoxyphenyl)-(4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)-methanone ( 18m) was designed and synthesized as a biologically stable derivative containing no ester group. Although the potency of 18m was almost the same as our initial hit compound 1, 18m is expected to last longer in the human body as an anticancer agent. A lead optimization program was carried out on a screening hit to discover novel type of anti-tumor agents.