Synthesis of 5-substituted quinazolinone derivatives and their inhibitory activity in vitro

Article abstract of DOI:10.1016/S0960-894X(98)00602-7

Quinazolinone derivatives I and their methyl esters were synthesized and evaluated as nonclassical lipophilic inhibitors of thymidylate synthase. Compounds Ib and Ic containing OH and CO₂H as R substituents, respectively, were most effective, indicating that hydrogen bonding may contribute to the increased inhibitory activity. These compounds further showed high cytotoxic activity against tumor cells in culture.