Series of N-substituted diethyl aspartates and N-substituted-3-oxo-1,4-piperazine-2-acetic
acid esters were synthesized as potential inhibitors of
aspartate transcarbamoylase. The aspartates were obtained by addition of substituted alkyl
amines to
diethyl maleate, or conversion of the hydroxy ethyl amino adduct to other functions. The 3-oxo-1,4-piperazine-2-acetic
acid esters were prepared by addition of
ethylene diamine to
diethyl maleate, followed by cyclization. Addition of 1,2-diamino-2-methylpropane gave the corresponding 5,5-dimethyl-3-oxo-1,4-piperazine-2-acetic
acid ester. N-Acyl derivatives in each series were obtained using the bromoacyl
chlorides. A majority of the compounds in each series showed antimicrobial activity against five representative microorganisms, as well as significant activity against
aspartate transcarbamoylase. Four of the compounds were found to have significant specificity against several tumor cell lines. A distance of two carbons between N and a reactive function was found to give the best activity for either antimicrobial, antienzyme, or
tumor cell specificity activities, in either the open chain aspartates or cyclic
piperazines. Little difference in anti-
enzyme activity was found between the aspartates and
piperazines, but introduction of the planar phenyl substituents lowered inhibitory activity.