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

  • Bioorg Med Chem Lett. 1998 Dec 1;8(23):3287-90. doi: 10.1016/s0960-894x(98)00602-7.
D J Baek  1 ,  Y K Park ,  H I Heo ,  M Lee ,  Z Yang ,  M Choi
Affiliations
  • 1. Drug Discovery Lab I, Choongwae Pharma Co., Suwon, Korea.
PMID: 9873719 DOI: 10.1016/s0960-894x(98)00602-7
Abstract

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.