Phenoxyacetic acid derivatives

A major use for 2,4-di-/ f2 -amylphenol is in the production of uv stabilizers the principal one is a benzotriazole-based uv absorber, 2-(2 -hydroxy-3, 5 -di-/ f2 -amylphenyl)-5-chlorobenzotriazole [25973-55-17, which is widely used in polyolefin films, outdoor furniture, and clear coat automotive finishes (56). Another significant use for 2,4-di-/ f2 -amylphenol is in the photographic iadustry. A number of phenoxyacetic acid derivatives of... 

Lehn and his coworkers have prepared a number of chiral cryptands based upon the 2,2 -binaphthyl unit " . In a typical preparation, the binaphthyl units are treated with bromoacetic acid to form the phenoxyacetic acid derivatives which are then converted into the corresponding diacyl chlorides (75). Reaction of 15 with l,10-diaza-18-... 

The search for more potent, selective and safe PPARa agonists has been challenging and only a limited number of compounds have progressed into the clinic. A number of phenoxyacetic acid derivatives and other diverse structures have emerged recently. Oral administration of LY-518674 (6) produced a 208% elevation in HDL and a 96% decrease in serum TG in apoA-I transgenic mice [38,39]. Recent clinical studies with compound 6 revealed a decrease in TG and an increase in HDL similar to fenofibrate. However, compound 6 also raised LDL-C in a dose-dependent fashion, and to a much higher level than seen with fenofibrate [28]. Both agents also raised serum creatinine levels above the upper limits of normal in 35-38% of patients [28]. 

Other carboxylic acids that have become popular herbicides, though they are not phenoxyacetic acid derivatives, are dicamba and glyphosate or Roundup . Notice that dicamba does have a methoxy group and two chlorines, so it is similar to 2,4-D. Glyphosate is used on cotton and... 

Ethacrynic acid is chemically distinct from the thiazides and furosemide but ceiling effect is similar. It is a phenoxyacetic acid derivative that also contains an adjacent ketone and methylene group. 

Ethacrynic acid—not a sulfonamide derivative—is a phenoxyacetic acid derivative containing an adjacent ketone and methylene group (Figure 15-7). The methylene group (shaded in figure) forms an adduct with the free sulfhydryl group of cysteine. The cysteine adduct appears to be an active form of the drug. 

The reverse situation - selective bioactivation in the uneconomic species — is realized in the selectively acting weedkillers of the phenoxybutyric acid type (Fig. 8). The butyric acid derivatives, as such, are inactive they have to be converted by 0-oxidation to the corresponding phenoxyacetic acid derivatives, which have the required auxin and hence weedkiller action. Since plant species... 

Ethacrynic acid (Table 10-11) is a powerful loop diuretic whose molecular mechanism of action is not fully clear. However, it has marked pharmacodynamic similarities to the mercurial diuretics such as merbaphen (see above) and mersalyl, both of which are also phenoxyacetic acid derivatives, as well as in vitro and in vivo comparability in its reaction with SH groups It competes with them for the same receptors. It is not surprising that an analogy, if not identity, of mechanism of action at the cellular level has been proposed. Equation 10.5, which illustrates a Michael-type addition, might represent a possible enzyme inactivation. 

With these compounds the carrrier of fungitoxicity, the dimethylthiocarbamate ion, could be introduced into the plant, but the antifungal activity of the compound in vitro is low. On the other hand, the compounds show growth-regulating properties similar to those of phenoxyacetic acid derivatives in vivo (Van der Kerk et... 

Tomacol differs with respect to selectivity from the phenoxyacetic acid derivatives discussed in the foregoing. It is recommended for selective weed control in vegetable crops, particularly in tomatoes. 

Inhibitors of Na -K -2Ct symport are chemically diverse. Furosemide (lasix), bumetanide (bumex), ethacrynic acid (edecrin), and torsemide (demadex) are available in the U.S. Furosemide and bumetanide contain a sulfonamide moiety, ethacrynic acid is a phenoxyacetic acid derivative, and torsemide is a sulfonylurea. 

A. Prototypes and Mechanism of Action Furosemide is the prototypic loop agent. Furosem-ide, bumetanide, and torsemide are sulfonamide derivatives. Ethacrynic acid is a phenoxyacetic acid derivative it is not a sulfonamide but acts by the same mechanism. Loop diuretics inhibit the cotransport of sodium, potassium, and chloride (Figure 15-4). The loop diuretics are relatively short-acting (diuresis usually occurs over a 4-hour period following a dose). 

Figure 5.1. Relationship between pKg values of substituted benzoic acids and their equivalent acetic acid and phenoxyacetic acid derivatives, o = o-substituted benzoic acids against o-substituted phenoxyacetic acids, x = m- and p-substituted benzoic acids against the corresponding phenoxyacetic acids. = p-substituted benzoic acids against a-substituted acetic acids.

Shapiro and co-workers [260, 261] reported the preparation of a large number of 2-phenoxybutyric acid derivatives which were tested for hypo-cholesterolemic activity in the guinea-pig. The most active compound in their first series of -acetamido-phenoxyacetic acid derivatives was XCIII. 

---