Synthesis of 5-substituted quinazolinone derivatives and their inhibitory activity in vitro.
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.
Baek
D J
DJ
Drug Discovery Lab I, Choongwae Pharma Co., Suwon, Korea.
Park
Y K
YK
Heo
H I
HI
Lee
M
M
Yang
Z
Z
Choi
M
M
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000138:chemical synthesis*; D006801:Humans; D051379:Mice; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D011799:Quinazolines; D013940:Thymidylate Synthase