Arylalkanoic acid derivatives

Flunoxaprofen is an NSAID, an arylalkanoic acid derivative. Its adverse effects profile is similar to the profiles of other NSAIDs, including gastrointestinal disturbances (1). 

Widespread use of naproxen, sulindac, diclofenac, and diflunisal probably explains why they were the most frequently rmphcated, rather than because they have a greater tendency to cause these adverse effects. NSAIDs differ in their ability to cause adverse skin reactions in terms of both frequency and severity pyrazolones, butazones, and oxicams are most often blamed, and among the arylalkanoic acid derivatives fenbufen and carprofen are most often incriminated. 

Essentially all the arylalkanoic acid derivatives that are therapeutically available are extensively metabolized. Metabolism occurs primarily through hepatic microsomal enzyme systems and may lead to deactivation or bioactivation of the parent molecules. Metabolism of each drug will be treated separately. 

ARYLALKANOIC ACID DERIVATIVES [SED IS, 2555 SEDA-32, 229 SEDA-33, 245 SEDA-34, 185, SEDA-35, 200] ... 

Monoalkyl ethers of (R,R) 1,2-bis[3,5-bis(trifluoromethyl)phenyl]ethanediol, 24, have been examined for the enantioselective protonation of silyl enol ethers and ketene disilyl acetals in the presence of SnCU (Scheme 12.21) [25]. The corresponding ketones and carboxylic acids have been isolated in quantitative yield. High enantioselectivities have been observed for the protonation of trimethylsilyl enol ethers derived from aromatic ketones and ketene bis(trimethylsilyl)acetals derived from 2-arylalkanoic acids. 

Although a previous chapter in this volume provides a broader perspective on the reactivity of radical cations, in this section we will examine intramolecular electron-transfer reactions coupled with or followed by cleavage of a bond in odd electron species such as radical cations, radical zwitterions and radical anions. In particular, this paragraph will be divided in oxidative and reductive bond-cleavage processes. Because this field is however too large to be covered extensively here, the discussion will be limited to selected examples—for oxidative cleavages, side-chain fragmentation reactions of alkylaromatic radical cations and decarboxylation reactions of radical zwitterions derived from benzoic and arylalkanoic acids, and for reductive... 

Radical zwitterions derived from arylalkanoic acids... 

Derivatives of 2,2-dimethyl-l,3-dioxan-4,6-dione (Meldrum s acid) and the sodium salts of substituted malonic esters undergo electrophilic C-arylation in high yield with aryllead triacetates this provides a useful route to a-arylalkanoic acids, compounds of interest in the pharmaceutical industry and as synthetic intermediates (Scheme 13.8) [36]. 

Aniinflammatory Analgesics - This class of compounds Is discussed in detail in Chapter 20. Studies of arylalkanoic acids and derivatives continue unabated. Details of analgesic testing of these agents are frequently incomplete. ... 

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