Diflubenzuron structure

Intestinal absorption of diflubenzuron in laboratory rats, measured as the sum of urinary and biliary excretion, decreases with increasing dose from 50% at a single oral dose of 4 mg/kg BW to 4% at 900 mg/kg BW. Excretion is almost complete after 75 h at that time, up to 4% of the administered dose is recovered from skinned carcasses (Willems etal. 1980). About 80% of diflubenzuron metabolites excreted by rats seem to have the basic diflubenzuron structure intact. Three metabolites are largely excreted as conjugates in the bile. One metabolite, 2,6-difluorobenzoic acid, is excreted largely in urine. Its counterpart, 4-chlorophenylurea, was not present in urine or bile in appreciable quantity, nor was 4-chloroaniline detected (Willems et al. 1980). Lifetime feeding studies of 4-chloroaniline, a relatively common diflubenzuron metabolite, showed no compound-related effects in laboratory mice and rats (Gartrell 1981). 

Several authors attempted to develop new and more effective compounds related chemically to diflubenzuron. Early quantitative structure-activity relationship analyses seemed to show that while the aniline moiety can be varied within wide limits, the benzoyl moiety is stringent in this respect and the 2,6-dihalogen substitution was thought to be indispensable for activity. The most active benzoylureas were those containing a 2, ifluorobenzoyl moiety combined with a... 

Diflubenzuron and its analogues aroused the interest of researchers engaged in quantitative structure-activity relationship (QSAR) studies. Thus, Verloop and Tipker (1977 1978) demonstrated on a number of diflubenzuron analogues the feasibility of STERIMOL parameters in QSAR analyses, permitting a refined insight into the shape of the substituents. Bordas et al. (1979) carried out a retrospective study of activity data on diflubenzuron derivatives, by using Free-Wilson analysis, factor analysis and principal component analysis. The factors extracted by principal component analysis and factor analysis were used as... 

Since the introduction of diflubenzuron by Phillips-Duphar in the mid 1970 s there has been considerable interest in the benzoyl-ureas. Current information suggests that they exert their effect on Insects by interfering with the formation of chitin, the primary structural component of the arthropod exoskeleton. The biochemical process that is responsible for chitin formation is shown in Figure... 

Modeling studies in our laboratory using the facilities of MDL s CHEMIAB suggest that the benzoylureas could mimic the uridine phosphates or UDP-N-acetylglucosamine at a binding site. The crystal structure of diflubenzuron was published in 1978 by Cruse [Cruse, 1978). Figure 4 is an ORTEP representation of that crystal structure. 

Figure 4. Diflubenzuron Crystal Structure (Reprinted with...

Diflubenzuron inhibits several enzyme systems in crab and insect larvae, resulting in disrupted glucose metabolism, reduced AGA incorporation into cuticle, and ultra-structural deformities of chitinous components of the cuticle. Specifically, diflubenzuron inhibits chitin synthetase, a magnesium-requiring enzyme that catalyzes the transfer of A-acetyl-D-glucosamine to chitin the final result is relatively large accumulations of AGAs. 

Metalaxyl is a member of a class of compounds that structurally resemble the chloroacetani-lides however, it is a systemic fungicide. Diflubenzuron is representative of a class of insecticides that owe their action to inhibition of chitin synthesis by the developing insect. Metalaxel and diflubenzuron are good examples of compounds prepared by the synthesis chemist as herbicide candidates that have commercial levels of activity in entirely different applications. Such examples point out the need for a balanced synthesis and screening program for the development of new agrochemicals. 

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