Insect juvenile hormone mimetic activity of (4-substituted)phenoxyalkyl compounds with various nitrogenous and oxygenous functions and its relationship to their electrostatic and stereochemical properties

We prepared classes of insect juvenile hormone (JH) mimetic compounds in which oxime, hydroxylamine, ester, amide, carbamate, and urea were built in at the alkane moiety of the 4-substituted phenyl alkyl ether structure. Some of them had effects on Culex pipiens as strong as those of the most active JH mimetics known. Calculation of the electrostatic potentials and stereochemical interpretations showed that the most active compound of each class was the entity in which the function in question was incorporated so that its negative potential peak was about 4.6 angstrom distant from the molecular edge within the framework of the receptor model drawn previously by us. The potency of alpha,beta-unsaturated esters was anomalously high when compared with that of the corresponding saturated esters, irrespective of the fact that both esters equally satisfy the electrostatic and stereochemical conditions. The reactivity properties of the unsaturated esters showed that this structure made the molecules resistant to hydrolysis, suggesting that the alpha,beta-unsaturated esters, like natural JHs and methoprene, owe much of their effect to this property.