Phenoxyacetic acid structure

The phenoxyacetic acid structure had been found to be a good carrying moiety in organic mercury diuretics. 

It was not until 1962 that the first quantitative structure-activity relationship was published by Corwin Hansch and co-workers [13], relating to the herbicidal activity of a series of phenoxyacetic acids ... 

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]. 

Statistical and computational methods have been used to quantify structure-activi relationships leading to quantitative structure-activity relationships (QSAR). The concqpt of QSAR can be dated back to the work of Crum, Brown and Fraser from 1868 to 1869, and Richardson, also in 1869. Many notable papers were published in the period leading up to the twentieth century by men such as Berthelot and Jungfleisch in 1872, Nemst in 1891, Ov ton in 1897 and Meyer in 1899 (7). Professor Corwin Hansch is now regarded by many as the father of QSAR, because of his work in the development of new and innovative techniques for QSAR. He and his co-woikers produced a paper that was to be known as the birtii of QSAR, and was oititled "Correlation of biological activity of phenoxyacetic acids with Hammett substituent constants and partition coefficients" (2). 

Problem 19.23 Write the structure for (a) phenoxyacetic acid, (h) phenyl acetate, (c) 2-hydroxy-3-phenylben-zoic acid, (d) p-phenoxyanisole. ... 

Crystal structures of the isostructural complexes [ZnfOH LJ (LH = phenoxyacetic acid or 4-chlorophenoxyacetic acid) have been reported, and the metal has been shown to be in a distorted octahedral Oe environment (108). 

Model Parent Compound Series. Experimental partition coefficient data for a variety of substituted benzenes and seven other related parent compound series (phenoxyacetic acid, phenylacetic acid, benzoic acid, benzyl alcohol, phenol, aniline, nitrobenzene) were reported in 1964 by Fujita et al. (II). The ir values (see Equation 3) derived for individual substituents in each of the above-mentioned parent compound series have since been frequently used (with varying degrees of success) by many investigators to approximate tt values for the corresponding substituents in other related parent compounds for which no experimental partitioning data are available. For example, Hansch and Deutsch (26), in a correlation study of structure—activity relationships in cholinesterase inhibitors, used tr values derived for aromatic ring substituents (X) in the phenoxyacetic acid series... 

Neely and Whitney (21) have similarly used the phenoxyacetic acid series w values in structure-activity correlations of the insecticidal activity of phenyl-O-methyl methylphosphoramidates ... 

The performance of the FBI can be enhanced by the use of (volatile) additives, such as ammonium acetate, formate, or oxalate, to the mobile phase [92]. They are assumed to act as carriers. Similarly, the use of additives with structures related to the target analyte structures, e.g., phenoxyacetic acid in the analysis of chlorophenoxyacetic acids, was evaluated as well [93]. The carrier effects, exerted by either mobile-phase additives, coeluting compounds, and/or isotopically-labelled standards, is not really understood from a mechanistic point of view. It caimot be applied to consistently enhance the performance for some compounds it works fine, while for others no effects are observed. 

Synonyms 2,4,5-Trichlorophenol Chemical/Pharmaceutical/Other Class Chlorinated phenoxyacetic acids. A closely related compound is 2,4-D (2,4-dichlorophenoxyacetic acid) Chemical Structure ... 

This is just in contrast to another approach of modifying the molecular structure of peptidic compounds on the biosynthetic level, namely the directed biosynthesis of the desired compound structures by feeding of appropriate biosynthetic precursors or stimulating agents during fermentation, as it is routinely performed for production of penicillin V und G by the addition of phenoxyacetic acid or phenyl-acetic acid, respectively, as precursors to facilitate penicillin extraction from the culture broth. 

While partition coefficients from many different organic solvent/water systems have been used in early structure-activity relationships, n-octanol became the organic solvent of choice after the pioneering work of Hansch on n-octanol/water partition coefficients of substituted phenoxyacetic acids and the lipophilicity parameter 7t derived from these partition coefficients [14, 15, 17, 18, 173, 180]. 

The discipline of quantitative structure-activity relationships (QSAR), as we define it nowadays, was initiated by the pioneering work of Corwin Hansch on growthregulating phenoxyacetic acids. In 1962—1964 he laid the foundations of QSAR by three important contributions the combination of several physicochemical parameters in one regression equation, the definition of the lipophilicity parameter jt, and the formulation of the parabolic model for nonlinear lipophilicity-activity relationships. 

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