[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, I1-7; X = NO2, II1-6) were prepared. Among them, 10 compounds showed antiarrhythmic effect on aconitine-induced arrhythmia in rats. The ED50(to stop VT) of I2 and ED50(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 (a1-7). After a1-7 were acetylated, the erythro type products(I1-7) were obtained.
Ren
Y
Y
Division of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009.
Hua
W Y
WY
Peng
S X
SX
Zhu
D Y
DY
Guo
Y L
YL
D000157:Aconitine; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy; D008968:Molecular Conformation; D015394:Molecular Structure; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D000889:Anti-Arrhythmia Agents; D010666:Phenylpropionates; D000157:Aconitine