Development of an Insect Growth Regulator, Chlorfluazuron

The authors, with the intention of exploring an insecticide bearing a new mechanism other than nervous system inhibition and hence possible low mammalian-toxicity, focused as a lead on the biological profile of the benzoylphenylurea (BPU) compounds during their research works and finally selected chlorfluazuron which was marketted against lepidopterous pests of vegetables and fruit trees in 1988 as Atabron® and also as Helix® and Aim® in Japan and foreign countries, respectively. At the time of the commencement of the exploration, the consideration was put on the following three attempts: 1. setting up of a new bio-assay system eligible for the detection of slow larvicidal activity specific to the BPU IGRs, 2. diversification of trifluoromethylpyridine intermediate already industrialized through the development of fluazifop-butyl, and 3. examination of utilization of a new chemorational design based on the trifluoromethylpyridine synthons as a building block for the molecule set-up. Chlorfluazuron selected among the closely related pyridyloxyphenyl-benzoylureas showed far surpassing insecticidal activity over the lead diflubenzuron against specific target insects such as lepidoptera, diptera and orthoptera at their larval stages by chitin biosynthesis inhibition mechanism. The detailed history before and after the exploration, larvicidal activity and selectivity, quantitative structure-activity relations, synthesis, toxicology etc. with respect to chlorfluazuron are discussed.