Quinazolinone-based compounds

Many quinazolinone-based compounds function as thymidylate synthase inhibitors by directly binding to the active site of thymidylate synthase. This results in the inhibition of DNA replication as well as DNA damage, S-phase cell arrest, and caspase-dependent apoptosis. Many compounds of this class have been successfully employed as anti-cancer pharmaceutics. Two examples, nolatrexed, a compound used to treat unresectable hepatocellular carcinoma (HCC), and raltitrexed, a first-line treatment against advanced colorectal cancer, are highlighted below. 

Benzoxazine-2,4-diones (43) (isatoic anhydrides) have proved useful synthons for various new heterocycles. For example, a base-catalyzed condensation with the oxindole (44) affords tetracycles (45) (80JHC1785), whereas the parent compound (43 R = H) and 3-hydroxyisothiazole give the quinazolinone (46) (69AJC2497). 

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