Synthesis of Tertiary Piperazine Aminoalcohols and their Dihydrochlorides and their Influence on DNA Methylation Processes In Vitro

Tertiary piperazine aminoalcohols were synthesized by reacting 1-(4-butoxyphenyl)-3-(4-substituted piperazin-1-yl)-2-phenylpropan-1-ones with alkyl(aryl)magnesium halides. Some of the final compounds were converted into dihydrochlorides. The influence of the synthesized compounds on C-180 mouse tumor DNA methylation was studied in vitro by incubating drug solutions (3 × 10^–6 M) with tumor homogenates at 37°C (thermostatted) for 24 h. Rather high activity (51.6% inhibition of DNA methylation) was observed for 1-(4-butoxyphenyl)-3-[4-(4-fluoropheny)piperazin-1-yl]-1,2-diphenylpropan-1-ol containing a 1-phenyl radical. Introduction of a methoxy group into the ortho-position of the phenyl radical decreased the activity to 37.5%.