DEVELOPMENT OF N,O-DISUBSTITUTED HYDROXYLAMINES AND N,N-DISUBSTITUTED AMINES AS INSECT JUVENILE-HORMONE MIMETICS AND THE ROLE OF THE NITROGENOUS FUNCTION FOR ACTIVITY

Insect juvenile hormone (JH) active N,O-disubstituted hydroxylamines were developed to examine the role of the nitrogenous function for high activity. They are O-alkyl-N-[(4-phenoxyphenoxy) and (4-benzylphenoxy)alkyl]hydroxylamines and reversely substituted N-alkyl-O-[(4-phenoxyphenoxy)-alkyl]hydroxylamines. The activity against Culex pipiens of the most potent member of each class was as high as that of the compounds known so far as the most active of JH mimics. When the overall length of the molecules is kept at the optimum, about 21 Å, suggested in our earlier works, the compounds having a hydroxylamino nitrogen atom, rather than the oxygen atom, at the δ-position from the central phenoxy oxygen atom or at the 4-position (about 4.6 Å) from the alkyl end showed about 10 times higher activity than those having the nitrogen atom at the position one atom missed the point. The corresponding amine compounds also prepared showed this more clearly, but their activity was considerably lower than that of the hydroxylamines. The lower potency of the amines with pKa?10 was attributed to their quarternization at physiological pH, preventing going to or binding with the action site. © 1990, American Chemical Society. All rights reserved.