Synthesis of 2-(4-substituted phenyl)-3-[4-substituted piperazino(piperidino)]propan-1-ol dihydrochlorides and their effects on adenosine deaminase activity

Abstract

Aminomethylation of 4-substituted acetophenones yielded a series of β-amino-4-substituted propiophenones. Reduction of these with lithium alumohydride in dry ether produced 1-(4-substituted phenyl)-3-[4-substituted piperazino(piperidino)]propan-1-ols, which were then converted to the corresponding dihydrochlorides. The abilities of these compounds to inhibit adenosine deaminase, a key enzyme in purine metabolism in living organisms, were studied. Some of the compounds had quite marked inhibitory effects on the enzyme. The abilities of the compounds synthesized here to inhibit adenosine deaminase were found to depend on their structure. It is of note that virtually all the compounds inhibited the high molecular weight form of the enzyme to a significantly lesser extent than the low molecular weight form.