Arylpropionic analgesics

Arylpropionic analgesic and anti-inflammatory drugs 6. GABAergic agonists... 

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). 

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). 

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. 

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. 

Alminoprofen is em arylpropionic acid analgesic/antiinflammatory agent indicated for the short term management of dental, traumatic and postpartum pain. 

Suprofen is an arylpropionic acid analgesic/antiinflammatory agent with close structural resemblance to ketoprofen. It is more potent in many eissays than indomethacin and ketoprofen and appears better tolerated. 

Ketoprofen, or 2-(3-benzoylphenyl)propionic acid, is a kind of 2-arylpropionic acid that represents an important group of nonsteroidal anti-inflammatory drugs (NSAIDs), and is widely used to relieve inflammation and pain resulting from arthritis, sunburn, menstrual pain, or fever. Previous studies have shown that its anti-inflammatory activity lies mainly in its (S)-enantiomer, while its (i )-enantiomer is a potentially highly potent analgesic treatment for neuropathie pain. Therefore, it is very valuable to obtain optically pure (S)- or (R)-ketoprofen. 

As mentioned above, ketoprofen is widely used in clinical practice as a nonsteroidal anti-inflammatory drug, like the other 2-arylpropionic acids such as naproxen and ibuprofen. The anti-inflammatory activity of ketoprofen was previously believed to reside in its (S)-enantiomer. However, research has indicated that the (f )-enantiomer of ketoprofen was able to prevent periodontal disease and was thus of pharmacological value as a toothpaste additive. It has also been discovered that (i )-ketoprofen has several previously unappreciated advantages as an analgesic and antipyretic. Another yeast strain, Citeromyces matriemis CGMCC 0573, was therefore isolated for the enantioselective hydrolysis of (i )-ketoprofen ethyl ester. ... 

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