755012-12-5Relevant academic research and scientific papers
Classical and three-dimensional QSAR for the inhibition of [ 3H]ponasterone a binding by diacylhydrazine-type ecdysone agonists to insect Sf-9 cells
Nakagawa, Yoshiaki,Takahashi, Kaoru,Kishikawa, Hidetoshi,Ogura, Takehiko,Minakuchi, Chieka,Miyagawa, Hisashi
, p. 1333 - 1340 (2005)
The activity of 52 diacylhydrazine congeners was evaluated by measuring the inhibition of the incorporation of [3H]ponasterone A into intact Sf-9 cells. Eleven compounds were newly synthesized in this study. Results showed that the substitution of the 2-CH3 or 3-OCH3 moiety of methoxyfenozide with other groups or the removal of either group was unfavorable to the activity. The activity was quantitatively analyzed using both classical QSAR (Hansch-Fujita) and three-dimensional QSAR methods (comparative molecular field analysis, CoMFA). Sterically favorable fields were observed at the 3- and 4-positions of the benzene ring opposite from the t-butyl group (B-ring), and a sterically unfavorable field was evidenced at the 2-position. Another sterically unfavorable field developed surrounding the favorable field observed at the 4-position of the B-ring. Electrostatically negative fields were observed near the CO moiety, above the benzene ring, and at the 4-position of the B-ring. The optimum hydrophobicity of compounds in terms of their log P values was calculated to be ≈4.1. Results of the three dimensional structure-activity relationship analyses were consistent with those obtained from the previously reported classical QSAR for 2-chlorobenzoyl analogs containing various para-substituents. The high activity of potent insecticides such as tebufenozide and chromafenozide were rationalized by CoMFA. Thus, this CoMFA result will be useful in the design of new compounds and in understanding the molecular mechanism of the ligand-receptor interactions.
Bioavailable diacylhydrazine ligands for modulating the expression of exogenous genes via an ecdysone receptor complex
-
Page/Page column 5, (2008/06/13)
The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.
