Development of (phenoxyphenoxy)- and (benzylphenoxy)propyl ethers as potent insect juvenile hormone mimetics

Development of (4-alkoxyphenoxy)- and (4-alkylphenoxy)alkanaldoxime O-ethers as potent insect juvenile hormone mimics and their structure-activity relationships

“…The replacement of the terminal aromatic moiety of the previous (4-phenoxyphenoxy)alkanaldoxime O-ether-type of compounds (Nakayama et al, 1985;Niwa et al, 1988) to alkoxys and alkyls gave a new class of JH mimics, the (4-alkoxyphenoxy)-and (4-alkylphenoxy)alkanaldoxime O-ethers. The optimum length of the whole molecule was estimated to be about 22 A, which coincided well with these lengths postulated for terpenoid (Nakayama et al, 1984), (4-phenoxyphenoxy)alkanaldoxime O-ether (Niwa et al, 1988), and (4phenoxyphenoxy)alkyl alkyl ether (Niwa et al, 1989) compounds. As in previous results (Niwa et al, 1988), the activity of the propionaldoximes was dozens of times higher than that of the corresponding acetaldoximes, suggesting that there was a position-specific interaction site on the surface of the JH receptor.…”

“…Development and JH Activity. The total length of the molecule is a basic and important factor for high JH activity (Nakayama et al, 1984(Nakayama et al, , 1985Niwa et al, 1988Niwa et al, , 1989. Coincidentally, in the (4-n-alkoxyphenoxy)acetaldoxime O-propyl ethers 1-8, n-propoxy 3, and n-butoxy 4 had higher activity than that with shorter or longer n-alkoxys.…”

“…We thus, prepared 3-(4-benzylphenoxy)propyl isobutyl ether (20) (D, Wx, and T2 being 20.8, 6.23, and 5.05 A, respectively) and 3- was replaced by a variety of alkoxy and alkyl groups, with the aim of further exploring the structural conditions for high potency of this part of the molecules and of developing new JH-active compounds. We obtained 3-(4-isobutylphenoxy)-, 3-[4-(2-ethylbutyl)phenoxy]-, and 3-(4neopentylphenoxy)propionaldoxime O-isopropyl ethers (35, 37, 39), the activity of which against Culex pipiens was as high as that of the previously developed 3-[4-(3methylphenoxy)phenoxy]propionaldoxime O-isopropyl ether (Niwa et al, 1988) and 3-[4-(3-methylphenoxy)phenoxy]propyl isobutyl ether (Niwa et al, 1989), which are the most active of the JH mimics known so far against this mosquito. The quantitative structure-activity relationship of the set of the compounds was analyzed to predict the potency from the structural factors.…”

3D-QSAR studies on the biological activity of juvenile hormone mimetic compounds for Culex pipiens Larvae

“…Regulation, transportation, and feedback control of the JH titer were seemed to be altered by the JHAs in many pest insects (Mundall et al, 1979;Ilenchuk and Davey, 1985). The roles of JHA on regulation and inhibition of protein synthesis have also been demonstrated in the hanogenates and the imaginal disk of Drosophila melanogastor (Niwa et al, 1988;Niwa et al, 1989). Ovicidal effects of JH and JHAs have been reported in Rhodnius prolixus (Niwa et al, 1990) and C. pipien.…”

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

“…In our developmental studies on a series of insect juvenile hormone (JH) mimetic compounds, (4-phenoxyphenoxy)-and (4-benzylphenoxy)alkanaldoximes (Niwa et al, 1988), (4-alkoxyphenoxy)-and (4-alkylphenoxy)alkanaldoximes (Hayashi et al, 1989), and (4-phenoxyphenoxy)-and (4-benzylphenoxy)alkyl alkyl ethers (Niwa et al, 1989), we found that the positions of the oxime and ether functions in a molecule are important for high activity. The positional effect has been clearly specified in the ether series of compounds to be at the 5-position from the common phenoxy oxygen atom; the activity against Culex pipiens of (phenoxyphenoxy)-and (benzylphenoxy)propyl propyl ethers was more than 10 times higher than that of the corresponding ethyl butyl and butyl ethyl ethers.…”