STRUCTURE ACTIVITY STUDIES ON 1,5-DISUBSTITUTED IMIDAZOLES AS INHIBITORS OF JUVENILE-HORMONE BIOSYNTHESIS IN ISOLATED CORPORA ALLATA OF THE COCKROACH DIPLOPTERA-PUNCTATA

The activity of eight substituted imidazoles as inhibitors of juvenile hormone III synthesis in the cockroach, Diploptera punctata, was measured in a short-term in vitro radiochemical assay. The potency of these compounds (IC50 of juvenile hormone III synthesis) ranged from 80 nM for KK-98 to 48 μM for KK-71. For some compounds (KK-71, KK-51), inhibition of juvenile hormone III synthesis was not accompanied by an accumulation of the immediate precursor methyl farnesoate within the glands. For other compounds (KK-83, KK-96, KK-98) significant accumulation (i.e., more than 100 pmol/pair) of methyl farnesoate was observed. The results suggest that some substituted imidazole compounds are selective inhibitors of the corpus allatum methyl farnesoate epoxidase at low concentrations, but all inhibit methyl farnesoate synthesis at higher concentrations. Experiments with farnesol and farnesoic acid, two precursors of juvenile hormone III synthesis, suggested that the imidazole compounds may inhibit farnesoic acid O-methyl transferase in addition to their predicted inhibition of the epoxidase. © 1990.