The use of substituent constants in the study of structure-activity relationships in cholinesterase inhibitors

Abstract

A quantitative analysis of the structure-activity relationship in cholinesterase inhibitors was made. From the results of Metcalf and Fukuto four different classes of inhibitors are considered: methylcarbamates, diethylphenylphosphates, alkylphosphonic acid esters, $\text{2,4,5-}\text{trichloro}\text{-N-}\text{alkylphosphoramidates}$. It is shown by means of substituent constants and regression analysis that the effects of substituent groups can be factored into three groups: electronic, steric, hydrophobic. The results indicate that the phosphate esters react by a mechanism different from that of the carbamates. New examples of the value of Taft's steric constant, $\text{E}{}_{\mathrm{<mtext>S</mtext>}}$, for biological reactions are discussed.