Solvent-free, microwave assisted synthesis of polyhalo heterocyclic ketene aminals as novel anti-cancer agents

Article abstract of DOI:10.1016/j.bmcl.2009.11.044

A series of polyhalo heterocyclic ketene aminals (polyhalo-HKAs) were synthesized under solvent-free conditions and evaluated in vitro against a panel of human tumor cell lines. Trifluoro-HKAs were the most cytotoxic compounds, followed by difluoro-HKAs and trichloro-HKAs. Trichloro-HKAs were more potent against the tumor cell lines Skov-3, Hep-2, K562, and A431 than difluoro-HKAs. An ethoxycarbonyl at the 2-position of the polyhalo HKAs gave the highest activity. Ethoxycarbonyl substituted 5o, bearing three fluorine atoms on the isophthalonitrile ring, was found to be the most potent derivative with IC₅₀ values lower than 3.7 μg/mL against five human tumor cell lines making it more active than cisplatin (DDP).