Abstract:
For the purpose of searching for new drug with high potency and simple chemical structure, the dominant conformation and structural parameters of Guan-Fu base (GFA) molecule were modelled and calculated with a SGI-4D 25G computer. The propanediolamine chain in GFA might be considered to be a pharmacophore responsible for the bioactivity and the configuration of the chain seemed important. Thus, thirteen compounds of (erythro)-p-x-PhCHOHCHOHCH
2NHR(x=H,I
1~7; X=NO
2, II
1~6) were prepared. Among them, 10 compounds showed antiarrhythmic effect on aconitine induced arrhythmia in rats. The ED
50(to stop VT) of I
2 and ED
50(to stop VP) of I
3 were shown to be comparable with those of GFA. In the synthesis, no stereoselectivity was found in the Prevost reaction with allylamine analogues (a
1~7). After a
1~7 were acetylated, the erythro type products(I
1~7) were obtained.