QUANTITATIVE STRUCTURE-ACTIVITY STUDIES OF INSECT GROWTH-REGULATORS XIV - 3-DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP OF ECDYSONE AGONISTS INCLUDING DIBENZOYLHYDRAZINE ANALOGS

N-tert-Butyl-N,N'-dibenzoylhydrazines such as tebufenozide (RH-5992) m imic the action of a molting hormone, 20-hydroxyecdysone, and cause pr emature molting of larvae leading to their death. Previously, it was s hown that one of the benzoyl moieties in dibenzoylhydrazines plays a r ole similar to that of the aliphatic side chain at the C-17 position o f ecdysones. In the present study, N-benzoyl-N'-benzylhydrazine, N,N'- dibenzylhydrazine, and N-alkanoyl-N'-benzoylhydrazine analogs have bee n synthesized to compare the effects of two carbonyl groups as well as two benzene rings of dibenzoylhydrazine. The quantitative structure-a ctivity relationship of ecdysone agonists including dibenzoylhydrazine analogs was analyzed three-dimensionally using the CoMFA (comparative molecular field analysis) procedure. The CoMFA results suggested that the two carbonyl oxygen atoms of the diacylhydrazine skeleton probabl y correspond to the oxygens of the 20- and 22-OH groups of ecdysones, and that the benzoyl moiety located closer to the tert-butyl group is important for retaining high activity. (C) 1998 SCI.