The Synthesis Of HBeAg Inhibitors

The antiviral treatment of chronic hepatitis B, a severe contagious disease, is a serious challenge to the scientists all over the world. Lamivudine is currently widely used as the treatment for patients with chronic hepatitis B, but has serious side-effects. The discovery of a new, safer and more effective antiviral drug has stimulated intensive efforts in this field.We synthesized eight new compounds, including five chain amine oxides and three cycloamine oxides, in order to optimize the lead compound which inhibits HBV DNA republication. And these compounds have molecular comparability, diversity and multi-supplement to the lead compound.These products, yielded from the alkylation of N-p-tolylacetamide, N-(2-methoxyphenyl)acetamide, N-(4-fluorophenyl)acetamide, N-(2-fluorophenyl) acetamide, and N-(naphthalene-1-yl) acetamide with 3-chloro-N,N-dimethylpropan-1- amine in the presence of NaH, were respectively oxided by H2O2 to N,N-dimethyl-3-(N-p-tolylacetamido)propan-1-amine oxide, 3-(N-(2-methoxyphenyl) acetamido)-N,N-dimethylpropan-1-amine oxide, 3-(N-(4-fluorophenyl)acetamido)- N,N-dimethylpropan-1-amine oxide, 3-(N-(2-fluorophenyl)acetamido)-N,N-dimethyl propan-1-amine oxide, and N,N-dimethyl-3-(n-(naphthalene-1-yl)acetamido) propan-1-amine oxide. 4-Acetyl-1-methylpiperazine 1-oxide, 4-butyryl-1- methyl piperazine 1-oxide, and 4-benzoyl-1-methylpiperazine 1-oxide were prepared by reacting 1-methylpiperzine dihydrochloride with acetyl chloride, butyryl chloride, and benzoyl chloride respectively, followed by H2O2 oxidation. The yields of these compounds are moderate. These compounds were analyzed by IR and 1H NMR. The biological screen against HIV and HBV had been taken. 3-(N-(4-fluorophenyl) acetamido)-N,N-dimethylpropan-1-amine oxide and N,N-dimethyl-3-(n-(naphthalene- 1-yl)acetamido)propan-1-amine oxide inhibit the secretion of HBeAg.