Sulfonylurea rates

Extensive use of two more recendy developed classes of herbicides will further dramatically reduce the amount of appHed to control weeds. The sulfonylurea herbicides are extremely active compounds first discovered in the mid-1970s at DuPont they have been discussed extensively (78). Sulfonjiurea herbicides have experienced a rapid and widespread success since thek commercial introduction in 1982 with chlorsulfuron (Table 5). The sulfonylureas are appHed at rates of 2—75 g/ha. The chemistry of the sulfonylurea molecule permits the synthesis of a very large number of useful analogues, consequentiy many new herbicides are anticipated for crop production. As of this writing (1996), over 350 patents have been issued to about 27 agricultural companies covering tens of millions of stmctures known or expected to be herbicidaHy active. 

Table 5. Application Rates of Sulfonylurea and Imidazoline Herbicides...

Another class of herbicides, the imida zolines, was discovered at American Cyanamid in the early 1980s. Extensive research has led to the development of four commercial compounds imazapyr, imazamethahenz-methyl, imazethapyr, and imazaquin (see Table 5). Like the sulfonylureas, the imidazolines are extremely active at low rates. 

Hydrolysis rates of sulfonylurea herbicides in water are heavily dependent upon pH. In general, acidic conditions promote faster hydrolysis, usually by cleavage of the sulfonylurea bridge. Neutral to alkaline conditions favor the compounds existing in... 

Monotherapy with sulfonylureas generally produce a 1.5% to 2% decline in HbAlc concentrations and a 60 to 70 mg/dL (3.33-3.89 mmol/L) reduction in FBG levels. Secondary failure with these drugs occurs at a rate of 5% to 7% per year as a result of continued pancreatic p-cell destruction. One limitation of sulfonylurea therapy is the inability of these products to stimulate insulin release from (1-cells at extremely high glucose levels, a phenomenon called glucose toxicity. 

The environmental impact of sulfonylurea herbicides is also of significance. Based on hydrolytic studies, Dinelli et al. [168] predicted the dissipation rate of four herbicides following aquifer contamination. The chemical... 

The sulfonylureas described here are new herbicides with unprecedented activity. Activity at extraordinarily low rates of application has been demonstrated by both preemergence and postemergence applications (Ref. 1). These rates are best describee in grams per hectare compared to kilograms per hectare for most herbicides currently marketed. Furthermore, the combination of low application rates, half lives of generally less than two months in the soil (Ref. 2) and excellent safety to mammals [LD5o s of generally >5000 mg/kg for technical material in male rats] (Ref. IC) makes these compounds attractive products from an environmental viewpoint. 

In summary, the sulfonylureas are new herbicides which exhibit activity at extremely low rates of application and show very low mammalian toxicity. Exceptionally high activity is shown by compounds containing a benzene ring substituted in the ortho position, an unsubstituted sulfonylurea bridge, and a pyrimidine or triazine heterocycle substituted with methyl or methoxy groups. 

Sales of agricultural products were 600 million in 1984. Du Pont expects to double this amount by 1990. There are many new products in the pipeline. Several of these new products are weed killers based on sulfonylurea chemistry. This family of weed killers is characterized by very low toxicity to mammals and high herbicidal activity at very low application rates in the field—often less than an ounce per acre of cropland. 

Some are inhibited by ATP 173 l7 lb and others by eicosanoids475 or inositol hexaphosphate.476 Some of the ATP-sensitive channels contain an ABC transporter subunit and are binding sites for sulfonylureas and other drugs. See discussion on p. 421. A number of human disorders in Kir channels have been identified.468 Tire human Kir channels participate in regulation of resting membrane potentials in K+ homeostasis, control of heart rate, and hormone secretion.468 A third group of K+ channels are dimeric, but each subunit contains two tandem P regions and 4-8 transmembrane helices.455... 

In the United Kingdom Prospective Diabetes Study a subgroup of patients taking sulfonylurea therapy to which metformin was added appeared to have had excess mortality. Data from 263 general practices in the UK were analysed 8488 patients took a sulfonylurea initially, to which metformin was added in 1868 (25). The crude mortality rates per 1000 person years were 59 and 40 respectively. Metformin was used initially in 3099 patients and a sulfonylurea was added in 867. The crude mortality rates per 1000 person years were 25 and 20 respectively. These results suggest there is no increased mortality risk with a combination of a sulfonylurea and metformin. 

There was a higher rate of hyperglycemia with gatiflox-acin or levofloxacin compared with ceftriaxone in a retrospective chart review of 17 000 patients (413). Sulfonylurea therapy was identified as an independent risk factor for hypoglycemia. 

Sulfonylureas undergo hydrolysis as shown in the mechanistic scheme in Figure 64 (106). Under acid-catalyzed conditions, water addition leads to loss of an amine and formation of a carbamic acid derivative. Acid-catalyzed loss of CO2 from the carbamic acid derivative yields the corresponding sulfonamide. It was proposed that initial protonation is the rate-determining step in the hydrolysis. 

Berger and Wolfe (1996) reported a correlation of hydrolysis data for 12 sulfonylurea herbicides. The use of bond strength or Hammett a constants was impossible because of the complex structures of the compounds. The hydrolysis pathways for this class of compounds are also more complex, but the use of quantum mechanical parameters provided the detailed structural information needed to develop a useful correlation. As a result of the many different functional groups, several reaction pathways are available depending on the substituents. Also, there is a complicating pH effect on the pathways and the kinetics of hydrolysis as shown by product studies. The 12 herbicides used in this study are listed in Table 13.4, and the pseudo first-order hydrolysis rate constants are given in Table 13.5. Figure 13.2 shows the basic structure of these compounds. 

Pseudo First-Order Hydrolysis Rate Constants with Standard Errors [(k + SE) x 10-2] in Aqueous Buffer Solutions for 12 Sulfonylurea Herbicides at Different pHs and Temperatures. 

The first ALS-resistant weeds were reported in 1987 when prickly lettuce (Mallory-Smith, 1990 Mallory-Smith et al, 1990b) and kochia (Primiani et al, 1990) control failures occurred in Idaho and Kansas, respectively, after 5 consecutive years of chlorsulfuron use. The kochia biotype proved to be cross-resistant to six other ALS-inhibitor herbicides, including sulfonylureas and imidazolinones. Within 5 years, sulfonylurea-resistant kochia had been identified at 832 sites in 11 states of the United States and in three Canadian provinces (Saari et al, 1994). ALS inhibitor-resistant kochia and Russian thistle have become widespread problems in cereal-producing regions of northwestern United States and Canada. The mobility of these tumble weeds as plants with mature seeds or pollen carried by wind has undoubtedly contributed to the rate at which resistance has spread. 

Gaeddert et al. (1997) found that cross-resistance of the ALS-resistant Palmer amaranth biotype occurred among 16 postemergence ALS herbicides evaluated. Sprague et al. (1995) found that two suspected resistant populations of Palmer amaranth and common waterhemp were resistant to imazethapyr and cross-resistant to the sulfonylureas, chlorimuron and thifensulfuron, at 10 times higher than labeled rates. 

D acid while the un-coated sulfonylurea crystals were rapidly decomposed in the same composition. While the process is very eflrcient and effective, it is not suited for research purposes. Less than one kilogram of powder per minute is not efficiently coated. Much higher rates of powder flow coat most effectively. 

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