Synthetic and cytotoxic studies of alpha-methylene-gamma-butyrolactone bearing pyrimidines.
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.
Huang
B R
BR
School of Chemistry, Kaohsiung Medical College, Taiwan, Republic of China.
Lee
K H
KH
Tseng
T L
TL
Wang
H M
HM
Chen
C F
CF
Tzeng
C C
CC
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D011743:Pyrimidines; C014096:alpha-methylene gamma-butyrolactone; D015107:4-Butyrolactone