1. Synthetic and cytotoxic studies of alpha-methylene-gamma-butyrolactone bearing pyrimidines.
- Author
-
Huang BR, Lee KH, Tseng TL, Wang HM, Chen CF, and Tzeng CC
- Subjects
- 4-Butyrolactone chemical synthesis, 4-Butyrolactone pharmacology, Antineoplastic Agents pharmacology, Humans, Pyrimidines pharmacology, Tumor Cells, Cultured drug effects, 4-Butyrolactone analogs & derivatives, Antineoplastic Agents chemical synthesis, Pyrimidines chemical synthesis
- Abstract
A total of ten pyrimidine alpha-methylene-gamma-butyrolactones were synthesized as potential antitumor agents on the basis of their possible action as Michael acceptors for DNA/RNA and cellular enzymes. The synthesis of these heterocycles involved a convenient Reformatsky-type reaction of pyrimidinyl ketones with ethyl alpha-(bromomethyl)acrylate. The preliminary in vitro cytotoxic assay indicated that these synthetic compounds were essentially active against the growth of KB, Hep-2, HeLa and Colo-205 cells. Among them, 5'-biphenyl-5'-(uracil-1-ylmethyl)-2'-oxo-3'-methylenetetrahydr ofuran (5f) demonstrated to be the most potent antileukemic agent.
- Published
- 1993