Naproxen drug class

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). 

Other inhibitors of COX are collected under the general term nonsteroidal antiinflammatory drugs (NS AlDs). Several of these are available OTC, including ibuprofen (Advil, Motrin), naproxen (Aleve), and ketoprofen (Orudis). About 25 drugs in this class have been approved for use in cliiucal medicine in the United States, including the four just mentioned. Others are available by prescription only. 

Apart from the salicylates NSAIDs include several classes of weak acids like propionic acid derivatives such as ibuprofen, carprofen, fenbufen, fenoprofen, flurbiprofen, ketorolac, loxoprofen, naproxen, oxaprozin, tiaprofenic acid and suprofen. Phenylbutazone is the most important representative of the pyrazolon derivatives which have a bad reputation for their risk of potentially fatal bone-marrow toxicity. To the acetic acid derivatives belong in-domethacin, diclofenac and sulindac. Sulindac is a pro-drug with less toxicity than indomethacin. The enolic acids include piroxicam, droxicam and tenoxicam. Meloxicam is an analog of piroxicam and has a high selectivity for COX-2. 

The 2-arylpropionic acid derivatives (profens) are important classes of NSAIDs that have been in clinical use for over 20 years. The profens have been used clinically as racemic agents with the exception of (S)-(+)-naproxen, which has been developed and used only as a single enantiomeric drug. 

Analgesics are a class of drugs that enhance our ability to tolerate pain without abolishing nerve sensations. Over-the-counter analgesics, such as aspirin, ibupro-fen, naproxen, and acetaminophen, inhibit the formation ofprostaglandins, which,... 

Polyphosphazenes are a relatively new class of biodegradable polymers. Their hydrolytic stability or instability is determined not by changes in the backbone structure but by changes in the side groups attached to an unconventional macromolecular backbone. Synthetic flexibility and versatile adaptability of polyphosphazenes make them unique for drug delivery applications. For example, Veronese et al.18 prepared polyphos-phazene microspheres with phenylalanine ethyl ester as a phosphorous substituent and loaded it with succinylsulphathiazole or naproxen. The kinetics of release from these matrices were very convenient in yielding local concentrations of the two drugs that are useful per se or when mixed with hydroxyapatite for better bone formation. Polyphosphazene matrices are also considered as potential vehicles for the delivery of proteins and vaccines.19... 

The asymmetric hydroformylation of vinyl arenes can provide a route to the preparation of the profen class of drugs. Naproxen and ibuprofen, two examples in the profen class, are NSAIDs on the market.50... 

An important example is the resolution of the enantiomers of naproxen. Naproxen is a member of a family of compounds known as Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) which are 2-aryl propionic acids. This class also includes ibuprofen, the painkiller developed by Boots and marketed as Nurofen. 

Applications to Products of Commercial Interest. (5)-Ethyl lactate has been incorporated in chiral syntheses of (5)-2-arylpropionic acids, an important class of nonsteroidal anti-inflammatory agents, including ibuprofen and naproxen (eq 12). These syntheses, though elegant in concept, are unlikely to compete with existing industrial methods for production of the (5) enantiomers of these drugs. 

A widely used technique for separating racemic mixture is the use of enzyme mediated transesterification or hydrolysis. One important example is the separation of Naproxen (33), which is a member of the 2-arylpropionic acid class of profens that are broadly used as NSAIDs (see Section 2 for the separation of enantiomers using a crystallization approach). The important association between chirality and biological activity of this class of drugs has been extensively researched, where... 

Simultaneous use of two analgesics of different modes of action is rational, but two drugs of the same class/mechanism of action are unlikely to benefit unless there is a difference in emphasis, e.g. analgesia and anti-inflammatory action (paracetamol plus aspirin), or in duration of action a patient taking an NSAID with a long duration, e.g. naproxen (used once or twice a day), is benefited by an additional drug of shorter duration for an acute exacerbation, e.g. ibuprofen, paracetamol. 

Aryl propionic acid nonsteroidal antiinflammatory drugs. The compounds from this class of agents that have been stereochemically resolved include ibuprofen, flurbiprofen, naproxen, benoxaprofen, pirprofen, su-profen, fenoprofen, indoprofen, and ketoprofen (94). 

In VIGOR, rofecoxib 50 mg/day was associated with a higher rate of non-fatal myocardial infarction (0.4%) than the non-selective COX-2 inhibitor naproxen 500 mg bd (0.1%) (RR = 0.2 Cl = 0.1, 0.7) (33). In CLASS there was no difference in the rates of myocardial infarction in patients taking celecoxib (0.5%) and those taking ibuprofen or diclofenac (0.4%). However, the protocols of the two studies differed substantially with respect to the use of aspirin. In VIGOR, the patients were not allowed to take aspirin or any other antiplatelet drug, while in... 

Nabumetone is a naproxen derivative, whose efficacy is related to its active metabolite, 6-methoxy-2-naphthyla-cetic acid. Not unexpectedly, a study in 2000 patients, mostly treated for more than 6 months, ehcited an adverse events pattern similar to the other derivatives of this class of NSAIDs (SEDA-13, 81). Adverse effects were reported in 18% of patients and 10% stopped taking the drug because of adverse reactions. Diarrhea was the most common problem (13%) followed by abdominal pain (9.9%), dyspepsia (9.3%), nausea (7.8%), and flatulence (4.7%). Ten ulcers were detected. Nervous system reactions, skin rashes, edema, unspecified eye disorders, and liver function test abnormahties aU occur (1). 

An important class of compounds that can be prepared by this route is the 2-arylpropionitriles, precursors for the widely used anti-inflammatory 2-arylpro-panoic acids [3]. Of these, only naproxen [( SJ-2-(6-methoxynaphthyl)propanoic acid] is sold as an optically pure drug. Nugent and McKinney first reported efficient syntheses of racemic ibuprofen and naproxen via the Ni[P(0-p-tolyl)3]4-catalyzed hydro cyanation of the corresponding vinylarene precursors (Scheme 2)... 

We describe the extension of this class of bisphosphite catalysts to asymmetric hydroformylation and hydrocyanation of vinylarenes.(3) These enantiose-lective catalytic transformations are employed for the asymmetric synthesis of S-Naproxen, a widely used non-steroidal anti-inflammatory drug (NSAID). Factors which influence regioselectivity and enantioselectivity, as well as characterization of the catalyst resting states, are discussed. 

Phenylpropionic acid is the simplest member ot the 2-arylpropionic acids class to which a number of widely used antiinflammatory drugs belongs. Important examples of non-steroidal analgesics are 2-(p-isobutylphenyl)-, 2-(m-benzoylphenyl)-and 2-(6-methoxy-2-naphthyl)propionic acids well known commercially as Ibuprofen, Ketoprofen, and Naproxen, respectively. 

The Zambon synthesis of the non-steroidal anti-inflammatory agent (5)-2-(6-methoxy-2-naphthyl)propanoic acid (naproxen) is a landmark-setting application of the chiral auxiliary approach in the industrial stereoselective synthesis of an enantiomerically pure drug [51]. The chiral auxiliary employed, a (2f ,Jf )-dialkyltartrate, is a paradigmatic representative of this class of stereocontroller, being cheap, readily available, easily introduced on the substrate and removed from the product, and eventually recycled (although as its parent acid). 

The 2-arylpropionic acid class (2-APA) of nonsteroidal anti-inflammatory drugs (NSAlDs) (Table 1) is characterized by each member having an asymmetric carbon a to the carboxylic acid moiety. The R-enantiomer of this chiral center of some 2-APAs may undergo an in vivo inversion to the S-enantiomer. This inversion process varies substantially between the different members of this class and also varies between species of animal studied. The members of this class that are currently in clinical use include ibuprofen, ketoprofen, tiaprofenic acid, fenoprofen, and flurbiprofen. The majority are marketed as racemates. Naproxen and its sodium salt are internationally marketed as the pure S(-l-)-enantiomer, while ibuprofen and ketoprofen are now marketed in several European countries as the stereochemically pure S(-l-)-enantiomer. 

---