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

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.