Structural studies on bioactive compounds. 1 Heck reactions on 4-methylenepyrazolo[5,1-c][1,2,4]triazines

Abstract

1-(3-Methyl-4-methylenepyrazolo[5,1-c][1,2,4]triazin-6(4H-yl)ethanone 9a and its 7-methyl- 9b and 7-phenyl-derivative 9c undergo Heck coupling to afford (Z)-1-{4-benzylidene-3-methylpyrazolo[5,1-c][1,2,4]triazin-6(4H)-yl}ethanones 10a–c and substituted benzylidene analogues 10d–m as the major geometrical isomers in low yields. The most potent agent in a human tumour screen in vitro was 10b (mean GI50 value 4.9 μM in a panel of 60 human cancer cell lines), with evidence of selective action against colon KM12 (GI50 0.02 μM) and breast MCF-7 tumour cell lines (GI501.35 μM).