Flurbiprofen

Hoiffmann-La Roche Co., AG, Switzerland British Patent 1,040,547 Sept. 1,1966 F. Hoffmann-La Roche Co., AG, Switzerland British Patent 1,040,548 Sept. 1,1966 Fryer, R. and Sternbach, L.H. U.S. Patent 3,567,710 March 2,1971 assigned to Hoffman-La Roche, Inc. 

Chemical Name 2-(2-Fluoro-4-biphenylyl)propionic acid 

Trade Name Manufacturer Country Year Introduced  

A mixture of 3-acetyl-2-fluorobiphenyl, MP 95°C to 96°C, (73.5 g) [prepared from 4-toromo- 

A sodium carbonate solution of the crude acetic acid was washed with ether and then acidified with hydrochloric acid the required acid was isolated via an ether extraction and was esterified by refluxing for 6 hr with ethanol (370 ml) and concentrated sulfuric acid (15 ml). Excess alcohol was distilled, the residue diluted with water and the required ester isolated in ether. Distillation finally gave ethyl 2-fluoro-4-biphenylacetate,BP 134°Cto 136°C/0.25 mm. 

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FLUOROBIPHENYLS Fluorobiphenyls are incorporated into the analgesic and antiinflammatory dmgs diflunisal [22494-42-4] and flurbiprofen [5104-49-4]. The first is a difluoro compound and the other monofluoro. 

Nonsteroidal Antiinflammatory Drugs. Nonsteroidal antiinflammatory dmgs (NSAIDs) include, among the numerous agents of this class, aspirin (acetylsaflcyhc acid), the arylacetic acids indomethacin and sulindac, and the arylpropionic acids, (5)-(147) and (R)-(148) ibuprofen, (5)-(149) and (R)- (150), flurbiprofen naproxen (41), and fenoprofen (see Analgesics, antipyretics, and antiinflammatory agents Salicylic acid and related compounds). 

The aluminum salts of dmgs are significant for two principal reasons reduction of dmg acidity in the stomach lining and reduction of undeskable flavor. Examples are the aluminum salts of glycine, acetylsahcyhc acid, ibuprofen, flurbiprofen, fenoprofen, flufenamic acid, oxaprozin, and a variety of aminobenzoic acid. Some of these compounds are Hsted in Table 2. 

Fluormated agents such as flurbiprofen (II), flunisal(i2), diflunisal (13), and sulindac (14), acting as prostaglandin synthesis mhibitors, have been available for some time [5] The recent introduction of flunoxaprafen (15), a lipoxygenase inhibitor, is notable It reportedly produces considerably less severe gastric disturbance [75]... 

Flurbiprofen and indomethacin, which comprise the third class of inhibitors, cause a slow, time-dependent inhibition of COX-1 and COX-2, apparently via formation of a salt bridge between a carboxylate on the drug and Arg , which lies in the tunnel. 

Electropherograms of a urine sample (8 ml) spiked with non-steroidal anti-inflammatory drugs (10 p-g/ml each) after direct CE analysis (b) and at-line SPE-CE (c). Peak identification is as follows I, ibuprofen N, naproxen K, ketoprofen P, flurbiprofen. Reprinted from Journal of Chromatography, 6 719, J. R. Veraait et al., At-line solid-phase exti action for capillary electrophoresis application to negatively charged solutes, pp. 199-208, copyright 1998, with permission from Elsevier Science. 

Diethylcarbamyl chloride Diethylcarbamazine citrate Diethyl carbonate Fenspiride Flurbiprofen Furaltadone Nifuratel Protizinic acid Diethylchlorophosphate Echothiopate iodide 0 ,0i -Dlethyl-4,4 -dihydroxystilbene Diethylstilbestrol diphosphate... 

A new brush-type CSP, the Whelk-0 1, was used by Blum et al. for the analytical and preparative-scale separations of racemic pharmaceutical compounds, including verapamil and ketoprofen. A comparison of LC and SFC revealed the superiority of SFC in terms of efficiency and speed of method development [50]. The Whelk-0 1 selector and its homologues have also been incorporated into polysiloxanes. The resulting polymers were coated on silica and thermally immobilized. Higher efficiencies were observed when these CSPs were used with sub- and supercritical fluids as eluents, and a greater number of compounds were resolved in SFC compared to LC. Compounds such as flurbiprofen, warfarin, and benzoin were enantioresolved with a modified CO, eluent [37]. 

Derivatized amylose is the basis for the Chiralpak AD CSP. This CSP has been utilized for the resolution of ibuprofen and flurbiprofen, as well as other members of the family of nonsteroidal inflammatory drugs (NSAIDs) [39, 61]. Ibuprofen was not resolved on the Chiralpak AD CSP in LC. Pressure-related effects on stereoselectivity were observed by Bargmann-Leyder et al. on a Chiralpak AD CSP [58]. No corresponding effect of pressure on selectivity was observed with a Chiralcel OD CSP. The authors speculated that the helical conformation of the amylose-based CSP is more flexible than that of the cellulose-based CSP. 

Other arylpropionic acids include naproxen, ketopro-fen and flurbiprofen. They share most of the properties of ibuprofen. The daily oral dose of ketoprofen is 50-150 mg, 150-200 mg for flurbiprofen and 250-1000 mg for naproxen. Whereas the plasma elimination half-life of ketoprofen and flurbiprofen are similar to that of ibuprofen (1.5-2.5 h and 2.4-4 h, respectively), naproxen is eliminated much more slowly with a half-life of 13-15 h. 

These drug are contraindicated in individuals with known hypersensitivity to an individual drug or any components of the drug. The NSA.ID flurbiprofen is contraindicated in patients with herpes simplex keratitis. Diclofenac and ketorolac are contraindicated in patients who wear soft contact lenses (may cause ocular irritation). 

Orthoformates have been used in the lipase-catalyzed esterification aimed at the kinetic resolution of racemic acids such as flurbiprofen, a nonsteroidal anti-inflammatory drug (Figure 6.18). Orthoformates trap the water as it is formed through hydrolysis, and therefore prevent the reverse reaction, and, at the same time, provide the alcohol for the esteriflcation [65]. 

C,4H]3N0 42771-78-8) see Flurbiprofen 2-acetylamino-6-chloro-5-nitro-4(31/)-pyrimidinone (C9HJCIN4O4 51471-45-5) see Abacavir iV-acetyl-4-amino-2,4-dideoxy-2,3-didehydroneuraminic acid... 

CjHioOj 105-58-8) see Ambuside Bisoprolol Fenspiride Flurbiprofen Furazolidone Ketoprofen Mephenytoin Nifuratel Pheno barbital Pranoprofen Protizinic acid Temafloxacin Toloxatone Tybamate Zolmitriptan... 

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