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 CO 2H as R substituents, respectively, were most effective, indicating that hydrogen bonding may contribute to the i...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 1998-12, Vol.8 (23), p.3287-3290
Main Authors: Baek, Du-Jong, Park, Yang-Kee, Heo, Hong Il, Lee, Myounghee, Yang, Zungyoon, Choi, Myounghee
Format: Article
Language:English
Subjects:
Animals
Antimetabolites, Antineoplastic - chemical synthesis
Antimetabolites, Antineoplastic - pharmacology
Antineoplastic agents
Biological and medical sciences
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - pharmacology
Folic Acid Antagonists - chemical synthesis
General aspects
Humans
Medical sciences
Mice
Pharmacology. Drug treatments
Quinazolines - chemical synthesis
Quinazolines - pharmacology
Structure-Activity Relationship
Thymidylate Synthase - antagonists & inhibitors
Tumor Cells, Cultured
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Summary: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 CO 2H 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. 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 CO 2H 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(98)00602-7