Seventeen substrates were synthesized and their activities as surrogate substrates for Neuropathy Target Esterase were tested. Substrates investigated are carbon analogs of phenylvalerate (1) with oxygen and sulfur substituted at the alpha, beta and gamma positions. Phenol and thiophenol esters of these analogs constitute two series of compounds tested. The ratio of catalytic hydrolysis to background hydrolysis increased at lower pH values with all substrates tested including phenylvalerate (1). There was more than a 2.5-fold increase in specific activity with phenylthiopropylethanoate (6) at pH of 6.75 compared to phenylvalerate (1). Furthermore, a 19-fold decrease in Km is reported with compound 6. This and related compounds can be used as the basis of more sensitive assays for neuropathy target esterase. Thiophenyl esters in this series are sufficiently good substrates to hold promise in continuous assays.