A library synthesis of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as anti-tumor agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 17; pp. 4383 - 4387
• Main Authors: Hayakawa, Ichiro, Shioya, Rieko, Agatsuma, Toshinori, Furukawa, Hidehiko, Naruto, Shunji, Sugano, Yuichi
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 06.09.2004; Elsevier
• Subjects: Anti-cancer; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Benzofurans - chemical synthesis; Biological and medical sciences; Carboxylic Acids - chemical synthesis; Cell Line, Tumor; Combinatorial Chemistry Techniques - methods; General aspects; Humans; Medical sciences; Miscellaneous; Pharmacology. Drug treatments; Anti-cancer; Antineoplastic agent; Combinatorial chemistry; Cytotoxicity; Selectivity; Liquid phase; In vitro; Screening; Ester; Cell line; Structure activity relation; Carboxylic acid; Chemical compound library; Benzofuran derivatives; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.06.067

A compound library for structure optimization was synthesized employing solution-phase parallel synthesis to find highly potent derivatives. As a result of a hit-to-lead program using a technique of solution-phase parallel synthesis, a highly potent (2,4-dimethoxyphenyl)-[6-(3-fluorophenyl)-4-hydroxy-3-methylbenzofuran-2-yl]methanone ( 15b) was synthesized as an optimized derivative of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester ( 1), which was discovered as a screening hit from small-molecule libraries and exhibited selective cytotoxicity against a tumorigenic cell line.