Analgesics flurbiprofen

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 optional site selective metallation of fluorotoluenes158 with the superbasic mixture of butyllithium and potassium fert-butoxide has been applied to the synthesis of the anti-inflammatory and analgesic drug Flurbiprofen.171 3-Fluorotoluene is selectively metallated in the 4-position with LIC-KOR in THF at — 75 °C to afford, after reaction with fluorodimethoxyborane and hydrolysis, the corresponding boronic acid in 78% yield. A palladium-catalyzed coupling with bromobenzene gives the 2-fluoro-4-methylbiphenyl in 84% yield. This four-step sequence can also be contracted to a one-pot procedure with an overall yield of 79%. A double metallation with the superbasic mixture lithium diisopropylamide/potassium tert-butoxide (LIDA-KOR)172 173 is then required to produce flurbiprofen. 

METHOTREXATE ANALGESICS-NSAIDs t methotrexate levels, with reports of toxicity, with ibuprofen, indome-tacin and possibly diclofenac, flurbiprofen, ketoprofen and naproxen Uncertain postulated that an NSAID-induced 1 in renal perfusion may have an effect Consider using an alternative NSAID... 

ANTACIDS ANALGESICS-NSAIDs 1. Magnesium hydroxide t absorption of ibuprofen, flurbiprofen, mefenamic acid and tolfenamic acid 2. Aluminium-containing antacids 1 absorption of these NSAIDs Uncertain These effects are 1 by taking these drugs with food... 

Flurbiprofen (oral) Adjunctive therapy providing anti-inflammatory and analgesic properties... 

Recently, data have been provided indicating thatR-flurfaiprofen may have analgesic activities similar to those of S-flurbiprofen (35). 

In the absence of its antipode, an enantiomer may exhibit greater pharmacological activity. This is possible when a less active enantiomer acts as an antagonist or one accelerates clearance of the other. For example, in the rat, the analgesic effects and plasma concentration of d-propoxy-phene are enhanced in the presence of /-propoxyphene (26). Conversely, as compared to the racemate, plasma concentrations of flurbiprofen enantiomer seem to increase when either enantiomer is given alone to both humans and rats (27,28). An opposite observation has been reported for indobufen in the rat and mouse (29),... 

Although the primary mode of action for NSAIDs is the inhibition of the COX enzymes, there now exists ample evidence that some of the effects of NSAIDs are not mediated by inhibition of PG formation at the site of inflammation. For example, for a number of NSAIDs, there is poor correlation between their analgesic potency and their capacity to inhibit PG production (McCormack 1994). This poor correlation between analgesic and anti-inflammatory effects can also be seen for enantiomers of some chiral NSAIDs. For example, the enantiomers of the NSAID flurbiprofen were shown to produce equipotent analgesia but the (R)-enantiomer possessed very little anti-inflammatory activity compared with the (S)-enantiomer (Brune et al 1992). It has been proposed that this differential analgesic activity is mediated by inhibition of PG synthesis within the CNS, as opposed to at the site of inflammation (Brune et al 1992). There is also some evidence that a unique CNS isoform of the COX enzyme exists (Flower et al 1985). 

Propionic acid propanoic acid) derivatives have been extensively developed since the original introduction of ibuprofen into clinical use. Other examples of those in clinical use include fenbufen, flurbiprofen, ketoprofen, naproxen and oxaprozin. Many of these agents have a relatively low incidence of reported side-effects, however, their usage varies. Ibuprofen is the first analgesic since paracetamol to be licensed in the UK for non-prescription use but such use is limited to the treatment of relatively minor pain states, even though it has fair antiinflammatory properties. Most other members are reserved for systemic use to treat rheumatoid and osteoarthritis, musculoskeletal pain and similar states (some applied topically). 

Benzylic C-C fragmentation typically occurs with arylacetic acids and with some phenethylamines. Arylacetic and (3-arylpropionic acids are a large family of antiinflammatory and analgesic drugs and easily decarboxylate. The benzyl radicals formed are reduced or trapped by oxygen. Typical examples are 2-phenylpropionic acids such as ibuprofen (Castell et al., 1987a) butibufen (Castell et al., 1992) and flurbiprofen, as well as the related naphthylpropionic acid naproxen (46, Scheme 4.32) (Moore and Chappuis, 1988). 

Fenoprofen (200 to 300 mg in divided doses b.i.d. or t.i.d.) is indicated for acute or long-term treatment of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Fenoprofen is a propionic acid derivative and, similar to ibupro-fen, naproxen, flurbiprofen, or ketoprofen, has analgesic, antipyretic, and antiinflammatory properties (see also Table 3). 

Like the arylacetic acids the arylpropionic acid analogues also exhibit potent anti-inflammatory properties besides usual antipyretic and analgesic characteristics. A few examples of this category of compounds are discussed here, flurbiprofen ketoprofen indoprofen fenoprofen calcium. 

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