Diflunisal derivative

Analgesics. Four examples of antiinflammatory agents are Sulindac [38194-50-2] based on a monofluoro indene derivative diflunisal... 

Acetylsalicylic ac/cf. Acetylsalicylic acid has been associated with Reye s syndrome. Because diflunisal is a salicylic acid derivative, the possibility of its association with Reye s syndrome cannot be excluded. 

Salicylic acid derivatives acetylsalicylic acid (ASA) diflunisal... 

Diazotization routes are mainly suited to the production of fluoroaromatics with only one or two fluorine atoms in the same ring. Two Or more fluorine atoms are often introduced via the nucleophilic displacement of chlorine atoms in an activated , i.e. electron-deficient, ring by fluoride ions. For example, the reaction of 2,4-dichloro-l-nitrobenzene with potassium fluoride has been used in the manufacture of 2,4-difluoro-l-nitrobenzene, an intermediate for the antiinflammatory aspirin derivative diflunisal (7). 

Diflunisal is a fluorinated salicyhc acid derivative, which is absorbed unchanged from the gastrointestinal tract, reaching peak concentrations after about 2 hours, and is metabolized by glucuronidation (1). Its adverse effects and other characteristics are those of aspirin, although gastrointestinal haemorrhage may be less common (2). 

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. 

Antiflammatories and analgesics such as Ampiroxicam from Pfizer and Toyama Chem. Co. (Ref. 65, 72) or a derivative of Diflunisal (Ref. 73)... 

V. Glucuronide-derived Covalent Binding of Diflunisal to Bladder Tissue of Rats and Its Modulation by Urinary pH and Beta-glucuronidase," Biochem. Pharmacol. 46(7), 1175-1182 (1993). 

Unfortunately, high-dosage chronic toxicity tests in rats and dogs resulted in gastrointestinal lesions and papillary necrosis. Clinical tests ceased. Reexamination of close analogs of flufenisal led to the selection of the 5-(2,4-difluorophenyl) derivative of salicylic acid—diflunisal. The additional fluorine atom may have compensated for loss of potency attributable to the lack of the O-acetyl group, which in turn probably accounts for... 

Diflunisal (dolobid) is a difluorophenyl derivative of salicylic acid (Figure 26-1). It is almost completely absorbed after oral administration, and peak plasma concentrations occur within 2-3 hours. It is extensively bound to plasma albumin (99%). About 90% of the drug is excreted as glucuronide conjugates, and its rate of elimination is dose-dependent. At the usual analgesic dose (500-750 mg/day), the plasma averages 8-12 hours. Diflunisal appears in the milk of lactating women. 

S. G. Kucukguzel, I. Kucukguzel, E. Tatar, S. RoUas, F. Sahin, M. GuUuce, E. De Clercq, and L. Kabasakal. Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and antiinflammatory agents. Eur. J. Med. Chem., 42(7) 893-901, July 2007. 

The salicylate NSAIDs, for example, aspirin, diflunisal, and salsalate, are derived from the relatively strong organic acid, salicylic acid, used first as the sodium salt and then replaced at the... 

Benzoic acid derivatives, such as aspirin and diflunisal (compounds 1 and 2)... 

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