Naproxene antiinflammatory drug

In contrast, the opposite result was observed when these materials were used in the acylation of a bulky substrate (2-methoxynaphthalene, 2-MN). In this case, l-acetyl-2-metoxynaphthalene (1-A,2-MN) and 6-acetyl-2-metoxynaphthalene (6-A,2-MN) are the main reaction products (Scheme 2). The latter is an intermediate for the preparation of Naproxen (antiinflammatory drug) and, therefore, the most interesting product. Initially, 2-MN acylation leads to 1-A,2-MN (the kinetically controlled product). However, at long times, the selectivity to 6-A,2-MN usually increases due to two secondary reactions transacylation of 1-A,2-MN with a molecule of 2-MN and protodeacylation of 1-A,2-MN yielding 2-MN [7],... 

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). 

Nonsteroidal antiinflammatory drugs (NSAIDs) are the mainstay of therapy because of their excellent efficacy and minimal toxicity with shortterm use. There is little evidence to support one NSAID as more efficacious than another, and three drugs (indomethacin, naproxen, and sulindac) have FDA approval for this indication (Table 1-1). 

Naproxen is a nonsteroidal antiinflammatory drug, and its (S )-form is about 30 times more active than its (R)-form. The Ru-BINAP-catalyzed asymmetric hydrogenation of substrate 36 offers an entry to an enantiomerically pure (.S ) To mi of the drug 37 (Scheme 6-20).lla... 

The asymmetric hydroformylation of aryl ethenes such as substituted styrene or naphthylethene is of industrial interest because the hydroformylation products of these substrates are precursors to important nonsteroidal antiinflammatory drugs such as (S )-ibuprofen and (S )-naproxen. Strong efforts have been made to improve the branched/linear ratio, as well as the enantioselectivity of the product. 

Analysis of non-steroidal anti-inflammatory drugs (ibuprofen, ketoprofen, naproxen, fenoprofen, flurbiproen, and suprofen) Impurity profiling of ketorolac, a chiral nonsteroidal antiinflammatory drug Impurity profiling of a non-steroidal analgesic drug... 

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. 

Co-codamol is a combination of paracetamol (nonnapioid analgesic) and codeine (opioid analgesic). One of the side-effects of opioids is constipation. Naprosyn is a proprietary (trade name) preparation of the non-steroidal antiinflammatory drug naproxen Adalat is a proprietary preparation of the calcium-channel blocker nifedipine Amoxil is a proprietary preparation of the beta-lactam amoxicillin and Dulco-lax is the brand name of the stimulant laxative bisacodyl. 

Aspirin (now a generic name) is one of a number of nonsteroidal antiinflammatory drugs (NSAIDs) others include ibuprofen and naproxen (see Fig. 21-15), all now sold over the counter. Unfortunately, aspirin reduces but does not eliminate the side effects of salicylates. In some patients, aspirin itself can produce stomach bleeding, kidney failure, and, in extreme cases, death. New NSAIDs with the beneficial effects of aspirin but without its side effects would be medically valuable. 

In spite of extensive studies on the asymmetric hydroformylation of olefins using chiral rhodium and platinum complexes as catalysts in early days, enantioselectivity had not exceeded 60% ee until the reaction of styrene catalyzed by PtCl2[DBP-DIOP (l)]/SnCl-> was reported to attain 95% ee in 1982 [8]. Although the value was corrected to 73% ee in 1983 [9], this result spurred further studies of the reaction in connection to possible commercial synthesis of antiinflammatory drugs such as (S)-ibuprofen and (S)-naproxen. The catalyst PtCl2[BPPM... 

V)-2-(4-Isobutylphenyl)propanal (17b) with 92% ee is obtained from p-isobutylstyrene (16b) by using the Rh-BINAPHOS catalyst, which is the precursor of antiinflammatory drug (S)-ibuprofen (entry 15) [19,64,65]. In a similar manner, the precursor of (S)-naproxen is obtained with 85% ee and excellent regioselectivity in the reaction of 16c catalyzed by Rh-(diphosphite 9) complex (entry 16) [25], Pentafluorostyrene (16e) is converted to the corresponding branched aldehyde 17e by the catalysis of the Rh-BINASPHOS complex with... 

The development of aspirin was a significant landmark in the history of medicine because it stimulated the development of a family of medicines, collectively known as the nonsteroidal antiinflammatory drugs (NSAIDs). NSAIDs such as ibuprofen, naproxen, and sulindac are valuable drugs used for the alleviation of pain, inflammation, and fever, and they are commonly prescribed for the treatment of rheumatoid disorders such as arthritis. The world market for NSAIDs now exceeds 6 billion (Vainio and Morgan, 1997). 

Naproxen was introduced to the market by Syntex in 1976 as a nonsteroidal antiinflammatory drug (NS AID) in an optically pure form. The original manufacturing process (Scheme 6.1) before product launch started from P-naphthol (1), which was brominated in methylene chloride to produce 1,6-dibromonaphthol (2). The labile bromine at the 1-position was removed with bisulfite to give... 

This conversion of a 1,2-diol to an epoxide has been used as an approach to 2-arylpropanoic acids, members of the nonsteroidal antiinflammatory drugs (NSAIDS) family of drugs.163 However, the sequence can be shortened by a selective hydrogenolysis, as illustrated for naproxen (20) (Scheme 9.24).164... 

S)-Naproxen (36), a potent nonsteroidal antiinflammatory drug (NSAID), is a best-selling agent for arthritis and represents a billion dollar a year market.50 Extensive research is aimed at the formation of the active 5-enantiomer because the /f-isomer is a potent liver teratogen. An asymmetric reduction has been proposed for the manufacture of 36 but has yet to be put into practice. Monsanto has reported that a 4-step manufacture process was in development for naproxen (Scheme 12.10).51... 

Nonsteroidal antiinflammatory drugs (ketoprofen, naproxen, flurbiprofen, indomethacin, ibuprofen) CEC Hypersil C18/SCX, 3 pm Acetonitrile-50 mM Na2HPC>4-water (60 20 20) 210 mm x 50 pm i.d. 138... 

Antiinflammatory drugs, such as aspirin, naproxen, and meclofenamate are useful in relieving migraine attack. 

The industrial synthesis of naproxen, an over-the-counter analgesic and antiinflammatory drug. 

Naproxen and ibuprofen are nonsteroidal antiinflammatory drugs (NSAIDs) widely available as and OTC medications. In both cases the active (S)-enantiomer is far more potent. Selective hydrolysis of racemic esters of these drugs enables the production of both (S)-naproxen and (S)-ibuprofen. A number of... 

Recently, ee s of 85-90% have been obtained for the asymmetric hydrocyanation of 6-methoxy-2-vinyhiaphthalene using nickel complexes of chiral bidentate phosphinites derived from glucose (abbreviated PP, equation 12). This reaction is of great interest to the pharmaceutical industry because the (S) enantiomer of the product nitrile is a useful precursor for the widely marketed antiinflammatory dmg naproxen (equation 13). The same reaction can be applied to a number of other vinyl aromatic compounds, including the precursor for the antiinflammatory drug ibuprofen (6) however, the ee is not as high. 

Goto et al. (67) synthesized the sucdnimidyl ester [14] of (—)- -methoxy-a-methyl-l-naphthaleneacetic acid for the normal-phase LC resolution of chiral amines. The reagent permitted the determination of the enantiomers of an amphetamine derivative in blood plasma after administration of racemic drug to rabbits. With detection at 280 nm, the lower limit of sensitivity was 5 ng/mL for each enantiomer (67). Several chiral acids from the "profen" group of nonsteroidal antiinflammatory drugs have been adapted as CDAs. One of these, naproxen, [15], is the S enantiomer and is commercially available as the resolved acid several of these acids have the advantage of providing fluorescent derivatives (68,69). 

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). 

Rhodium complexes of the ligand a,a-TREDIP (2) give very high iso regioselectivity in the hydroformylation of styrene under mild conditions, and this has been extended to the synthesis of 2 -(2-methoxy-6-naphthyl)propanal (3), a precursor of the antiinflammatory drug naproxen." ... 

NSAIDs (nonsteroidal antiinflammatory drugs) Isolated cases of adverse neurological side effects have been seen with naproxen or phenylbutazone given with misoprostol. Misoprostol also increases the abdominal pain and other side effects of diclofenac and indometacin (indomethacin). Paracetamol (acetaminophen) intensifies pain if given with mifepristone and sulprostone used to induce abortion. 

Because the aldehyde group is an extremely versatile functionality, AH constitutes a useful entree into chiral biologically active compounds such as the nonsteroidal antiinflammatory drug (S)-naproxen (32), commonly called Aleve. Section 9-7-1 highlighted a racemic hydrofomylation that was a key step in the synthesis of ibu-profen. naproxen is quite similar to ibuprofen in structure, but the toxic nature of racemic Naproxen in the body demands that it be synthesized and administered as the much less toxic (S)-enantiomer. Scheme 12.14 shows a possible route to 32, first involving AH of the vinyl naphthalene in the presence of BINAPHOS (34, Fig. 12-6) to create the chiral branched aldehyde and then subsequent oxidative conversion of the aldehyde to the carboxylic acid.83 AH of vinylnaphthalene (33)... 

Naproxen was introduced to the market by Syntex in 1976 as a nonsteroidal antiinflammatory drug in an optically pure form. The original manufacturing process (Scheme 1) before product launch started from P-naphthol (1) which was brominated in methylene chloride to produce 1,6-dibromonaphthol (2). The labile bromine at the 1-position was removed with bisulfite to give 2-bromo-6-hydroxy-naphthalene that was then methylated with methyl chloride in water-isopropanol to obtain 2-bromo-6-methoxynaphthalene (3) in 85-90% yield from p-naphthol. The bromo compound was treated with magnesium followed by zinc chloride. The resultant naphthylzinc was coupled with ethyl bromopropionate to give naproxen ethyl ester that was hydrolyzed to afford the racemic acid 4. The final optically active naproxen (5) was obtained by a classic resolution process. The racemic acid 4 was treated with cinchonidine to fonn diastereomeric salts. The S -naproxen-cinchonidine salt was crystallized and then released with acid to give S -naproxen (5) in 95% of the theoretical yield (48% chemical yield) [8,9]. 

Arylacetic acids are susceptible to light induced decarboxylation and this reactivity has been reported for the antiinflammatory drugs Naproxen (395) and Indomethacin (396). Photolysis of Naproxen or its potassium salt in methanol under anaerobic conditions gave 2-ethyl-6-methoxynaphthalene and 2-methoxy-... 

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