SYNTHESIS AND ANTIARRHYTHMIC ACTIVITY OF SOME (ERYTHRO)-PHENYLPROPANEDIOLAMINE COMPOUNDS

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-PhCHOHCHOHCH₂NHR(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 I₂ and ED_{50(to stop VP)} of I₃ 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.