{[1-(Arylmethyl)piperidin-4-yl]oxy}-(trifluoromethyl)-pyridines: ketanserin analogues with insect growth regulating activity.

A series of {[1-(arylmethyl)piperidin-4-yl]oxy}-(trifluoromethyl)-pyridine derivatives were designed and synthesized on the basis of the ketanserin (1) framework, a prototypic mammalian 5-HT(2A) receptor antagonist, and the structure-activity relationship (SAR) was also discussed. The result of the bioassay showed that most of the title compounds inhibited the insect growth and exhibited moderate-to-good growth regulating activity against the armyworm Pseudaletia separata Walker. Furthermore, the SAR study revealed that, when the determinant feature, interacting with mammalian 5-HT(2A) receptor, was preserved, a simplified ArCH(2) group greatly contributed to insect growth inhibitory activities. It was also found that the substituted position of the CF(3) group at the pyridine ring played a key role, and that the introduction of 1-[bis(4-fluorophenyl)methyl]piperazine, an equivalent of the benzoylpiperidine moiety of ketanserin, resulted in bioactivities similar to those of the title compounds, which were in agreement with the model of ketanserin analogues binding to mammalian 5-HT(2) receptors.